Journal articles: 'Reassortment'

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Lycett, S. J., G. Baillie, E. Coulter, S. Bhatt, P. Kellam, J. W. McCauley, J. L. N. Wood, I. H. Brown, O. G. Pybus, and A. J. Leigh Brown. "Estimating reassortment rates in co-circulating Eurasian swine influenza viruses." Journal of General Virology 93, no. 11 (November 1, 2012): 2326–36. http://dx.doi.org/10.1099/vir.0.044503-0.

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Swine have often been considered as a mixing vessel for different influenza strains. In order to assess their role in more detail, we undertook a retrospective sequencing study to detect and characterize the reassortants present in European swine and to estimate the rate of reassortment between H1N1, H1N2 and H3N2 subtypes with Eurasian (avian-like) internal protein-coding segments. We analysed 69 newly obtained whole genome sequences of subtypes H1N1–H3N2 from swine influenza viruses sampled between 1982 and 2008, using Illumina and 454 platforms. Analyses of these genomes, together with previously published genomes, revealed a large monophyletic clade of Eurasian swine-lineage polymerase segments containing H1N1, H1N2 and H3N2 subtypes. We subsequently examined reassortments between the haemagglutinin and neuraminidase segments and estimated the reassortment rates between lineages using a recently developed evolutionary analysis method. High rates of reassortment between H1N2 and H1N1 Eurasian swine lineages were detected in European strains, with an average of one reassortment every 2–3 years. This rapid reassortment results from co-circulating lineages in swine, and in consequence we should expect further reassortments between currently circulating swine strains and the recent swine-origin H1N1v pandemic strain.

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Barrat-Charlaix, Pierre, Timothy G. Vaughan, and Richard A. Neher. "TreeKnit: Inferring ancestral reassortment graphs of influenza viruses." PLOS Computational Biology 18, no. 8 (August 19, 2022): e1010394. http://dx.doi.org/10.1371/journal.pcbi.1010394.

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When two influenza viruses co-infect the same cell, they can exchange genome segments in a process known as reassortment. Reassortment is an important source of genetic diversity and is known to have been involved in the emergence of most pandemic influenza strains. However, because of the difficulty in identifying reassortments events from viral sequence data, little is known about its role in the evolution of the seasonal influenza viruses. Here we introduce TreeKnit, a method that infers ancestral reassortment graphs (ARG) from two segment trees. It is based on topological differences between trees, and proceeds in a greedy fashion by finding regions that are compatible in the two trees. Using simulated genealogies with reassortments, we show that TreeKnit performs well in a wide range of settings and that it is as accurate as a more principled bayesian method, while being orders of magnitude faster. Finally, we show that it is possible to use the inferred ARG to better resolve segment trees and to construct more informative visualizations of reassortments.

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Macken, Catherine A., Richard J. Webby, and William J. Bruno. "Genotype turnover by reassortment of replication complex genes from avian Influenza A virus." Journal of General Virology 87, no. 10 (October 1, 2006): 2803–15. http://dx.doi.org/10.1099/vir.0.81454-0.

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Reassortment among the RNA segments of Influenza A virus caused the two most recent human influenza pandemics; recently, reassortment has generated viral genotypes associated with outbreaks of avian H5N1 influenza in Asia and Europe. A statistical analysis has been developed for the systematic identification and characterization of reassortant viruses. The analysis was applied to the genes of the replication complex of 152 avian influenza A viruses isolated between 1966 and 2004 from predominantly terrestrial and domestic aquatic avian species. The results indicated that reassortment among these genes was pervasive throughout this period and throughout both the Eurasian and North American lineages of the virus. Evidence is presented that the circulating genotypes of the replication complex are being replaced continually by novel genotypes created by reassortment. No constraints for coordinated reassortment among genes of the replication complex were evident; rather, reassortment almost always proceeded one segment at a time. A maximum-likelihood estimate of the rate of reassortment was derived. For significantly diverged Asian avian influenza A viruses from the period 1991–2004, it was estimated that the median duration between creation of a new genotype and its next segment reassortment was 3 years. Reassortments that introduced previously unobserved influenza genetic material were detected. These findings point to substantial potential for rapid generation of novel avian influenza A viruses, emphasizing the importance of intensive surveillance of these host species in preparation for a possible pandemic.

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WAN, XIU-FENG, MUFIT OZDEN, and GUOHUI LIN. "UBIQUITOUS REASSORTMENTS IN INFLUENZA A VIRUSES." Journal of Bioinformatics and Computational Biology 06, no. 05 (October 2008): 981–99. http://dx.doi.org/10.1142/s0219720008003813.

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The influenza A virus is a negative-stranded RNA virus composed of eight segmented RNA molecules, including polymerases (PB2, PB1, PA), hemagglutinin (HA), nucleoprotein (NP), neuraminidase (NA), matrix protein (MP), and nonstructure gene (NS). The influenza A viruses are notorious for rapid mutations, frequent reassortments, and possible recombinations. Among these evolutionary events, reassortments refer to exchanges of discrete RNA segments between co-infected influenza viruses, and they have facilitated the generation of pandemic and epidemic strains. Thus, identification of reassortments will be critical for pandemic and epidemic prevention and control. This paper presents a reassortment identification method based on distance measurement using complete composition vector (CCV) and segment clustering using a minimum spanning tree (MST) algorithm. By applying this method, we identified 34 potential reassortment clusters among 2,641 PB2 segments of influenza A viruses. Among the 83 serotypes tested, at least 56 (67.46%) exchanged their fragments with another serotype of influenza A viruses. These identified reassortments involve 1,957 H2N1 and 1,968 H3N2 influenza pandemic strains as well as H5N1 avian influenza virus isolates, which have generated the potential for a future pandemic threat. More frequent reassortments were found to occur in wild birds, especially migratory birds. This MST clustering program is written in Java and will be available upon request.

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Tao, Hui, Lian Li, Maria C. White, John Steel, and Anice C. Lowen. "Influenza A Virus Coinfection through Transmission Can Support High Levels of Reassortment." Journal of Virology 89, no. 16 (June 3, 2015): 8453–61. http://dx.doi.org/10.1128/jvi.01162-15.

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ABSTRACTThe reassortment of gene segments between influenza viruses increases genomic diversity and plays an important role in viral evolution. We have shown previously that this process is highly efficient within a coinfected cell and, given synchronous coinfection at moderate or high doses, can give rise to ∼60 to 70% of progeny shed from an animal host. Conversely, reassortmentin vivocan be rendered undetectable by lowering viral doses or extending the time between infections. One might also predict that seeding of transmitted viruses into different sites within the target tissue could limit subsequent reassortment. Given the potential for stochastic factors to restrict reassortment during natural infection, we sought to determine its efficiency in a host coinfected through transmission. Two scenarios were tested in a guinea pig model, using influenza A/Panama/2007/99 (H3N2) virus (wt) and a silently mutated variant (var) thereof as parental virus strains. In the first, coinfection was achieved by exposing a naive guinea pig to two cagemates, one infected with wt and the other with var virus. When such exposure led to coinfection, robust reassortment was typically seen, with 50 to 100% of isolates carrying reassortant genomes at one or more time points. In the second scenario, naive guinea pigs were exposed to a cagemate that had been coinoculated with wt and var viruses. Here, reassortment occurred in the coinoculated donor host, multiple variants were transmitted, and reassortants were prevalent in the recipient host. Together, these results demonstrate the immense potential for reassortment to generate viral diversity in nature.IMPORTANCEInfluenza viruses evolve rapidly under selection due to the generation of viral diversity through two mechanisms. The first is the introduction of random errors into the genome by the viral polymerase, which occurs with a frequency of approximately 10−5errors/nucleotide replicated. The second is reassortment, or the exchange of gene segments between viruses. Reassortment is known to occur readily under well-controlled laboratory conditions, but its frequency in nature is not clear. Here, we tested the hypothesis that reassortment efficiency following coinfection through transmission would be reduced compared to that seen with coinoculation. Contrary to this hypothesis, our results indicate that coinfection achieved through transmission supports high levels of reassortment. These results suggest that reassortment is not exquisitely sensitive to stochastic effects associated with transmission and likely occurs in nature whenever a host is infected productively with more than one influenza A virus.

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Dlugolenski, Daniel, Les Jones, Elizabeth Howerth, David Wentworth, S. Mark Tompkins, and Ralph A. Tripp. "Swine Influenza Virus PA and Neuraminidase Gene Reassortment into Human H1N1 Influenza Virus Is Associated with an Altered Pathogenic Phenotype Linked to Increased MIP-2 Expression." Journal of Virology 89, no. 10 (March 11, 2015): 5651–67. http://dx.doi.org/10.1128/jvi.00087-15.

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ABSTRACTSwine are susceptible to infection by both avian and human influenza viruses, and this feature is thought to contribute to novel reassortant influenza viruses. In this study, the influenza virus reassortment rate in swine and human cells was determined. Coinfection of swine cells with 2009 pandemic H1N1 virus (huH1N1) and an endemic swine H1N2 (A/swine/Illinois/02860/09) virus (swH1N2) resulted in a 23% reassortment rate that was independent of α2,3- or α2,6-sialic acid distribution on the cells. The reassortants had altered pathogenic phenotypes linked to introduction of the swine virus PA and neuraminidase (NA) into huH1N1. In mice, the huH1N1 PA and NA mediated increased MIP-2 expression early postinfection, resulting in substantial pulmonary neutrophilia with enhanced lung pathology and disease. The findings support the notion that swine are a mixing vessel for influenza virus reassortants independent of sialic acid distribution. These results show the potential for continued reassortment of the 2009 pandemic H1N1 virus with endemic swine viruses and for reassortants to have increased pathogenicity linked to the swine virus NA and PA genes which are associated with increased pulmonary neutrophil trafficking that is related to MIP-2 expression.IMPORTANCEInfluenza A viruses can change rapidly via reassortment to create a novel virus, and reassortment can result in possible pandemics. Reassortments among subtypes from avian and human viruses led to the 1957 (H2N2 subtype) and 1968 (H3N2 subtype) human influenza pandemics. Recent analyses of circulating isolates have shown that multiple genes can be recombined from human, avian, and swine influenza viruses, leading to triple reassortants. Understanding the factors that can affect influenza A virus reassortment is needed for the establishment of disease intervention strategies that may reduce or preclude pandemics. The findings from this study show that swine cells provide a mixing vessel for influenza virus reassortment independent of differential sialic acid distribution. The findings also establish that circulating neuraminidase (NA) and PA genes could alter the pathogenic phenotype of the pandemic H1N1 virus, resulting in enhanced disease. The identification of such factors provides a framework for pandemic modeling and surveillance.

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Müller, Nicola F., Ugnė Stolz, Gytis Dudas, Tanja Stadler, and Timothy G. Vaughan. "Bayesian inference of reassortment networks reveals fitness benefits of reassortment in human influenza viruses." Proceedings of the National Academy of Sciences 117, no. 29 (July 6, 2020): 17104–11. http://dx.doi.org/10.1073/pnas.1918304117.

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Reassortment is an important source of genetic diversity in segmented viruses and is the main source of novel pathogenic influenza viruses. Despite this, studying the reassortment process has been constrained by the lack of a coherent, model-based inference framework. Here, we introduce a coalescent-based model that allows us to explicitly model the joint coalescent and reassortment process. In order to perform inference under this model, we present an efficient Markov chain Monte Carlo algorithm to sample rooted networks and the embedding of phylogenetic trees within networks. This algorithm provides the means to jointly infer coalescent and reassortment rates with the reassortment network and the embedding of segments in that network from full-genome sequence data. Studying reassortment patterns of different human influenza datasets, we find large differences in reassortment rates across different human influenza viruses. Additionally, we find that reassortment events predominantly occur on selectively fitter parts of reassortment networks showing that on a population level, reassortment positively contributes to the fitness of human influenza viruses.

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Ding, Xiao, Xuye Yuan, Longfei Mao, Aiping Wu, and Taijiao Jiang. "FluReassort: a database for the study of genomic reassortments among influenza viruses." Briefings in Bioinformatics 21, no. 6 (November 27, 2019): 2126–32. http://dx.doi.org/10.1093/bib/bbz128.

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Abstract Genomic reassortment is an important genetic event in the generation of emerging influenza viruses, which can cause numerous serious flu endemics and epidemics within hosts or even across different hosts. However, there is no dedicated and comprehensive repository for reassortment events among influenza viruses. Here, we present FluReassort, a database for understanding the genomic reassortment events in influenza viruses. Through manual curation of thousands of literature references, the database compiles 204 reassortment events among 56 subtypes of influenza A viruses isolated in 37 different countries. FluReassort provides an interface for the visualization and evolutionary analysis of reassortment events, allowing users to view the events through the phylogenetic analysis with varying parameters. The reassortment networks in FluReassort graphically summarize the correlation and causality between different subtypes of the influenza virus and facilitate the description and interpretation of the reassortment preference among subtypes. We believe FluReassort is a convenient and powerful platform for understanding the evolution of emerging influenza viruses. FluReassort is freely available at https://www.jianglab.tech/FluReassort.

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Nelson, Martha I., Susan E. Detmer, David E. Wentworth, Yi Tan, Aaron Schwartzbard, Rebecca A. Halpin, Timothy B. Stockwell, et al. "Genomic reassortment of influenza A virus in North American swine, 1998–2011." Journal of General Virology 93, no. 12 (December 1, 2012): 2584–89. http://dx.doi.org/10.1099/vir.0.045930-0.

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Revealing the frequency and determinants of reassortment among RNA genome segments is fundamental to understanding basic aspects of the biology and evolution of the influenza virus. To estimate the extent of genomic reassortment in influenza viruses circulating in North American swine, we performed a phylogenetic analysis of 139 whole-genome viral sequences sampled during 1998–2011 and representing seven antigenically distinct viral lineages. The highest amounts of reassortment were detected between the H3 and the internal gene segments (PB2, PB1, PA, NP, M and NS), while the lowest reassortment frequencies were observed among the H1γ, H1pdm and neuraminidase segments, particularly N1. Less reassortment was observed among specific haemagglutinin–neuraminidase combinations that were more prevalent in swine, suggesting that some genome constellations may be evolutionarily more stable.

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Kim, Kyoung Hee. "Jennerian reassortment rotavirus vaccines." Korean Journal of Pediatric Infectious Diseases 3, no. 1 (1996): 23. http://dx.doi.org/10.14776/kjpid.1996.3.1.23.

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Ganti, Ketaki, Anish Bagga, Juliana DaSilva, Samuel S. Shepard, John R. Barnes, Susan Shriner, Katia Koelle, and Anice C. Lowen. "Avian Influenza A Viruses Reassort and Diversify Differently in Mallards and Mammals." Viruses 13, no. 3 (March 19, 2021): 509. http://dx.doi.org/10.3390/v13030509.

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Reassortment among co-infecting influenza A viruses (IAVs) is an important source of viral diversity and can facilitate expansion into novel host species. Indeed, reassortment played a key role in the evolution of the last three pandemic IAVs. Observed patterns of reassortment within a coinfected host are likely to be shaped by several factors, including viral load, the extent of viral mixing within the host and the stringency of selection. These factors in turn are expected to vary among the diverse host species that IAV infects. To investigate host differences in IAV reassortment, here we examined reassortment of two distinct avian IAVs within their natural host (mallards) and a mammalian model system (guinea pigs). Animals were co-inoculated with A/wildbird/California/187718-36/2008 (H3N8) and A/mallard/Colorado/P66F1-5/2008 (H4N6) viruses. Longitudinal samples were collected from the cloaca of mallards or the nasal tract of guinea pigs and viral genetic exchange was monitored by genotyping clonal isolates from these samples. Relative to those in guinea pigs, viral populations in mallards showed higher frequencies of reassortant genotypes and were characterized by higher genotype richness and diversity. In line with these observations, analysis of pairwise segment combinations revealed lower linkage disequilibrium in mallards as compared to guinea pigs. No clear longitudinal patterns in richness, diversity or linkage disequilibrium were present in either host. Our results reveal mallards to be a highly permissive host for IAV reassortment and suggest that reduced viral mixing limits avian IAV reassortment in a mammalian host.

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Postnikova, Yulia, Anastasia Treshchalina, Elizaveta Boravleva, Alexandra Gambaryan, Aydar Ishmukhametov, Mikhail Matrosovich, Ron A. M. Fouchier, Galina Sadykova, Alexey Prilipov, and Natalia Lomakina. "Diversity and Reassortment Rate of Influenza A Viruses in Wild Ducks and Gulls." Viruses 13, no. 6 (May 27, 2021): 1010. http://dx.doi.org/10.3390/v13061010.

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Influenza A viruses (IAVs) evolve via point mutations and reassortment of viral gene segments. The patterns of reassortment in different host species differ considerably. We investigated the genetic diversity of IAVs in wild ducks and compared it with the viral diversity in gulls. The complete genomes of 38 IAVs of H1N1, H1N2, H3N1, H3N2, H3N6, H3N8, H4N6, H5N3, H6N2, H11N6, and H11N9 subtypes isolated from wild mallard ducks and gulls resting in a city pond in Moscow, Russia were sequenced. The analysis of phylogenetic trees showed that stable viral genotypes do not persist from year to year in ducks owing to frequent gene reassortment. For comparison, similar analyses were carried out using sequences of IAVs isolated in the same period from ducks and gulls in The Netherlands. Our results revealed a significant difference in diversity and rates of reassortment of IAVs in ducks and gulls.

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Glass, R., J. Gentsch, and J. Smith. "Rotavirus vaccines: success by reassortment?" Science 265, no. 5177 (September 2, 1994): 1389–91. http://dx.doi.org/10.1126/science.8073280.

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He, Dongchang, Xiyue Wang, Huiguang Wu, Xiaoquan Wang, Yayao Yan, Yang Li, Tiansong Zhan, et al. "Genome-Wide Reassortment Analysis of Influenza A H7N9 Viruses Circulating in China during 2013–2019." Viruses 14, no. 6 (June 9, 2022): 1256. http://dx.doi.org/10.3390/v14061256.

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Reassortment with the H9N2 virus gave rise to the zoonotic H7N9 avian influenza virus (AIV), which caused more than five outbreak waves in humans, with high mortality. The frequent exchange of genomic segments between H7N9 and H9N2 has been well-documented. However, the reassortment patterns have not been described and are not yet fully understood. Here, we used phylogenetic analyses to investigate the patterns of intersubtype and intrasubtype/intralineage reassortment across the eight viral segments. The H7N9 virus and its progeny frequently exchanged internal genes with the H9N2 virus but rarely with the other AIV subtypes. Before beginning the intrasubtype/intralineage reassortment analyses, five Yangtze River Delta (YRD A-E) and two Pearl River Delta (PRD A-B) clusters were divided according to the HA gene phylogeny. The seven reset segment genes were also nomenclatured consistently. As revealed by the tanglegram results, high intralineage reassortment rates were determined in waves 2–3 and 5. Additionally, the clusters of PB2 c05 and M c02 were the most dominant in wave 5, which could have contributed to the onset of the largest H7N9 outbreak in 2016–2017. Meanwhile, a portion of the YRD-C cluster (HP H7N9) inherited their PB2, PA, and M segments from the co-circulating YRD-E (LP H7N9) cluster during wave 5. Untanglegram results revealed that the reassortment rate between HA and NA was lower than HA with any of the other six segments. A multidimensional scaling plot revealed a robust genetic linkage between the PB2 and PA genes, indicating that they may share a co-evolutionary history. Furthermore, we observed relatively more robust positive selection pressure on HA, NA, M2, and NS1 proteins. Our findings demonstrate that frequent reassortment, particular reassorted patterns, and adaptive mutations shaped the H7N9 viral genetic diversity and evolution. Increased surveillance is required immediately to better understand the current state of the HP H7N9 AIV.

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White, Maria C., Hui Tao, John Steel, and Anice C. Lowen. "H5N8 and H7N9 packaging signals constrain HA reassortment with a seasonal H3N2 influenza A virus." Proceedings of the National Academy of Sciences 116, no. 10 (February 13, 2019): 4611–18. http://dx.doi.org/10.1073/pnas.1818494116.

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Influenza A virus (IAV) has a segmented genome, which (i) allows for exchange of gene segments in coinfected cells, termed reassortment, and (ii) necessitates a selective packaging mechanism to ensure incorporation of a complete set of segments into virus particles. Packaging signals serve as segment identifiers and enable segment-specific packaging. We have previously shown that packaging signals limit reassortment between heterologous IAV strains in a segment-dependent manner. Here, we evaluated the extent to which packaging signals prevent reassortment events that would raise concern for pandemic emergence. Specifically, we tested the compatibility of hemagglutinin (HA) packaging signals from H5N8 and H7N9 avian IAVs with a human seasonal H3N2 IAV. By evaluating reassortment outcomes, we demonstrate that HA segments carrying H5 or H7 packaging signals are significantly disfavored for incorporation into a human H3N2 virus in both cell culture and a guinea pig model. However, incorporation of the heterologous HAs was not excluded fully, and variants with heterologous HA packaging signals were detected at low levels in vivo, including in naïve contact animals. This work indicates that the likelihood of reassortment between human seasonal IAV and avian IAV is reduced by divergence in the RNA packaging signals of the HA segment. These findings offer important insight into the molecular mechanisms governing IAV emergence and inform efforts to estimate the risks posed by H7N9 and H5N8 subtype avian IAVs.

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McCullers, Jonathan A., Takehiko Saito, and Amy R. Iverson. "Multiple Genotypes of Influenza B Virus Circulated between 1979 and 2003." Journal of Virology 78, no. 23 (December 1, 2004): 12817–28. http://dx.doi.org/10.1128/jvi.78.23.12817-12828.2004.

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ABSTRACT The segmented genome of influenza B virus allows exchange of gene segments between cocirculating strains. Through this process of reassortment, diversity is generated by the mixing of genes between viruses that differ in one or more gene segments. Phylogenetic and evolutionary analyses of all 11 genes of 31 influenza B viruses isolated from 1979 to 2003 were used to study the evolution of whole genomes. All 11 genes diverged into two new lineages prior to 1987. All genes except the NS1 gene were undergoing linear evolution, although the rate of evolution and the degree to which nucleotide changes translated into amino acid changes varied between lineages and by gene. Frequent reassortment generated 14 different genotypes distinct from the gene constellation of viruses circulating prior to 1979. Multiple genotypes cocirculated in some locations, and a sequence of reassortment events over time could not be established. The surprising diversity of the viruses, unrestricted mixing of lineages, and lack of evidence for coevolution of gene segments do not support the hypothesis that the reassortment process is driven by selection for functional differences.

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Neumann, Gabriele, Margaret A. Green, and Catherine A. Macken. "Evolution of highly pathogenic avian H5N1 influenza viruses and the emergence of dominant variants." Journal of General Virology 91, no. 8 (August 1, 2010): 1984–95. http://dx.doi.org/10.1099/vir.0.020750-0.

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Highly pathogenic avian H5N1 viruses have circulated in South-east Asia for more than a decade and have now spread to more than 60 countries. The evolution of these viruses is characterized by frequent reassortment of the so-called ‘internal’ genes, creating novel genotypes. Additionally, over time, the surface glycoprotein, haemagglutinin (HA), which is the primary target of the adaptive immune response, has evolved by point mutation into 20 genetically and potentially antigenically distinct clades. To investigate the evolution of avian H5N1 influenza viruses, we undertook a high-resolution analysis of the reassortment of internal genes and evolution of HA of 651 avian H5N1 viruses from 2000 to 2008. Our analysis suggested: (i) all current H5N1 genotypes were derived from a single, clearly defined sequence of initial reassortment events; (ii) reassortment of just three of the internal genes had the most importance in avian H5N1 virus evolution; (iii) HA and the constellation of internal genes may be jointly important in the emergence of dominant variants. Further, our analysis led to the identification of evolutionarily significant molecular changes in the internal genes that may be significant for the emergence of these dominant variants.

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Zhou, Zhaorui, Fei Deng, Na Han, Hualin Wang, Surong Sun, Yujiang Zhang, Zhihong Hu, and Simon Rayner. "Reassortment and migration analysis of Crimean–Congo haemorrhagic fever virus." Journal of General Virology 94, no. 11 (November 1, 2013): 2536–48. http://dx.doi.org/10.1099/vir.0.056374-0.

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Crimean–Congo haemorrhagic fever virus (CCHFV) is a tick-borne virus with high pathogenicity to humans. CCHFV contains a three-segment [small (S), medium (M) and large (L)] genome and is prone to reassortment. Investigation of identified reassortment events can yield insight into the evolutionary history of the virus, while migration events reflect its geographical dissemination. While many studies have already considered these issues, they have investigated small numbers of isolates and lack statistical support for their findings. Here, we consider a larger set of 30 full genomes to investigate reassortment using recombination methods, as well as two sets of partial S segments comprising 393 isolates, reflecting a broader geographical range, to investigate migration events. Phylogenetic analysis revealed that the S segment showed strong geographical subdivision, but this was less apparent in the M and L segments. A total of 16 reassortment events with 22 isolates were identified with strong statistical support. Migration analysis on the partial S segments identified both long- and short-range migration events that spanned the entire geographical region in which the CCHFV has been isolated, reflecting the complex processes associated with the dissemination of the virus.

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BURT, F. J., J. T. PAWESKA, B. ASHKETTLE, and R. SWANEPOEL. "Genetic relationship in southern African Crimean-Congo haemorrhagic fever virus isolates: evidence for occurrence of reassortment." Epidemiology and Infection 137, no. 9 (January 23, 2009): 1302–8. http://dx.doi.org/10.1017/s0950268808001878.

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SUMMARYCrimean-Congo haemorrhagic fever (CCHF) is a tick-borne viral zoonosis widely distributed in Africa, Asia and eastern Europe. Reassortment of CCHF genome segments has been shown to occur in nature. We therefore investigated the genetic relationship of southern African isolates using partial sequence data for each RNA segment, S, M and L, and comparing the tree topologies constructed using a neighbour joining method. A total of 21 southern African isolates were studied. The incongruencies which were identified in S, M and L sequence datasets involved group switching implying reassortment for 15 isolates. A higher fatality rate occurred in patients infected with isolates which had apparently acquired M segments from a group in which predominantly Asian strains are usually found. This suggests that reassortment may affect the pathogenicity of the virus.

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Gischke, Marcel, Reiner Ulrich, Olanrewaju I. Fatola, David Scheibner, Ahmed H. Salaheldin, Beate Crossley, Eva Böttcher-Friebertshäuser, Jutta Veits, Thomas C. Mettenleiter, and Elsayed M. Abdelwhab. "Insertion of Basic Amino Acids in the Hemagglutinin Cleavage Site of H4N2 Avian Influenza Virus (AIV)—Reduced Virus Fitness in Chickens is Restored by Reassortment with Highly Pathogenic H5N1 AIV." International Journal of Molecular Sciences 21, no. 7 (March 28, 2020): 2353. http://dx.doi.org/10.3390/ijms21072353.

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Highly pathogenic (HP) avian influenza viruses (AIVs) are naturally restricted to H5 and H7 subtypes with a polybasic cleavage site (CS) in hemagglutinin (HA) and any AIV with an intravenous pathogenicity index (IVPI) ≥ 1.2. Although only a few non-H5/H7 viruses fulfill the criteria of HPAIV; it remains unclear why these viruses did not spread in domestic birds. In 2012, a unique H4N2 virus with a polybasic CS 322PEKRRTR/G329 was isolated from quails in California which, however, was avirulent in chickens. This is the only known non-H5/H7 virus with four basic amino acids in the HACS. Here, we investigated the virulence of this virus in chickens after expansion of the polybasic CS by substitution of T327R (322PEKRRRR/G329) or T327K (322PEKRRKR/G329) with or without reassortment with HPAIV H5N1 and H7N7. The impact of single mutations or reassortment on virus fitness in vitro and in vivo was studied. Efficient cell culture replication of T327R/K carrying H4N2 viruses increased by treatment with trypsin, particularly in MDCK cells, and reassortment with HPAIV H5N1. Replication, virus excretion and bird-to-bird transmission of H4N2 was remarkably compromised by the CS mutations, but restored after reassortment with HPAIV H5N1, although not with HPAIV H7N7. Viruses carrying the H4-HA with or without R327 or K327 mutations and the other seven gene segments from HPAIV H5N1 exhibited high virulence and efficient transmission in chickens. Together, increasing the number of basic amino acids in the H4N2 HACS was detrimental for viral fitness particularly in vivo but compensated by reassortment with HPAIV H5N1. This may explain the absence of non-H5/H7 HPAIV in poultry.

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Fuller, Trevon L., Marius Gilbert, Vincent Martin, Julien Cappelle, Parviez Hosseini, Kevin Y. Njabo, Soad Abdel Aziz, Xiangming Xiao, Peter Daszak, and Thomas B. Smith. "Predicting Hotspots for Influenza Virus Reassortment." Emerging Infectious Diseases 19, no. 4 (April 2013): 581–88. http://dx.doi.org/10.3201/eid1904.120903.

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Khiabanian, Hossein, Vladimir Trifonov, and Raul Rabadan. "Reassortment Patterns in Swine Influenza Viruses." PLoS Currents 1 (October 21, 2009): RRN1008. http://dx.doi.org/10.1371/currents.rrn1008.

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Khiabanian, Hossein, Vladimir Trifonov, and Raul Rabadan. "Reassortment Patterns in Swine Influenza Viruses." PLoS ONE 4, no. 10 (October 7, 2009): e7366. http://dx.doi.org/10.1371/journal.pone.0007366.

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Tao, H., J. Steel, and A. C. Lowen. "Intrahost Dynamics of Influenza Virus Reassortment." Journal of Virology 88, no. 13 (April 16, 2014): 7485–92. http://dx.doi.org/10.1128/jvi.00715-14.

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Conceição-Neto, Nádia, João Rodrigo Mesquita, Mark Zeller, Claude Kwe Yinda, Francisco Álvares, Sara Roque, Francisco Petrucci-Fonseca, et al. "Reassortment among picobirnaviruses found in wolves." Archives of Virology 161, no. 10 (July 20, 2016): 2859–62. http://dx.doi.org/10.1007/s00705-016-2987-4.

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Svinti, Victoria, James A. Cotton, and James O. McInerney. "New approaches for unravelling reassortment pathways." BMC Evolutionary Biology 13, no. 1 (2013): 1. http://dx.doi.org/10.1186/1471-2148-13-1.

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Matsuzaki, Y., K. Mizuta, K. Sugawara, E. Tsuchiya, Y. Muraki, S. Hongo, H. Suzuki, and H. Nishimura. "Frequent Reassortment among Influenza C Viruses." Journal of Virology 77, no. 2 (January 15, 2003): 871–81. http://dx.doi.org/10.1128/jvi.77.2.871-881.2003.

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ABSTRACT In a 9-year survey from December 1990 to December 1999 in Sendai City, Japan, we succeeded in isolating a total of 45 strains of influenza C virus. These 45 strains were isolated in clusters within 4 months in a year, especially from winter to early summer. Previous studies of the hemagglutinin-esterase genes of various influenza C virus isolates revealed the existence of five distinct virus lineages (Aichi/1/81-, Yamagata/26/81-, Mississippi/80-, Sao Paulo/82-, and Kanagawa/1/76-related lineage) in Japan between 1970 and the early 1990s (Y. Matsuzaki, K. Mizuta, H. Kimura, K. Sugawara, E. Tsuchiya, H. Suzuki, S. Hongo, and K. Nakamura, J. Gen. Virol. 81:1447-1452, 2000). Antigenic and genetic analyses of the 45 strains showed that they could be divided into these five virus lineages and a few antigenic groups were cocirculating in Sendai City. In 1990 and 1991 the dominant antigenic group was the Aichi/1/81 virus group, and in 1992 it was Yamagata/26/81 virus group. The Mississippi/80 virus group was isolated from 1993 to 1996, and the Yamagata/26/81 virus group reemerged in 1996 and continued to circulate until 1999. This finding led us to a speculation that the replacement of the dominant antigenic groups had occurred by immune selection within the human population in the restricted area. Phylogenetic analysis of seven RNA segments showed that 44 viruses among the 45 strains isolated in our surveillance work were reassortant viruses that have various genome compositions distinguishable from those of the reference strains of the each lineage. This observation suggests that the reassortment between two different influenza C virus strains occurs frequently in nature and the genome composition of influenza C viruses may influence their ability to spread in humans.

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Kopanke, Jennifer, Justin Lee, Mark Stenglein, and Christie Mayo. "In Vitro Reassortment between Endemic Bluetongue Viruses Features Global Shifts in Segment Frequencies and Preferred Segment Combinations." Microorganisms 9, no. 2 (February 16, 2021): 405. http://dx.doi.org/10.3390/microorganisms9020405.

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Bluetongue virus (BTV) is an arthropod-borne pathogen that is associated with sometimes severe disease in both domestic and wild ruminants. Predominantly transmitted by Culicoides spp. biting midges, BTV is composed of a segmented, double-stranded RNA genome. Vector expansion and viral genetic changes, such as reassortment between BTV strains, have been implicated as potential drivers of ongoing BTV expansion into previously BTV-free regions. We used an in vitro system to investigate the extent and flexibility of reassortment that can occur between two BTV strains that are considered enzootic to the USA, BTV-2 and BTV-10. Whole genome sequencing (WGS) was coupled with plaque isolation and a novel, amplicon-based sequencing approach to quantitate the viral genetic diversity generated across multiple generations of in vitro propagation. We found that BTV-2 and BTV-10 were able to reassort across multiple segments, but that a preferred BTV-2 viral backbone emerged in later passages and that certain segments were more likely to be found in reassortant progeny. Our findings indicate that there may be preferred segment combinations that emerge during BTV reassortment. Moreover, our work demonstrates the usefulness of WGS and amplicon-based sequencing approaches to improve understanding of the dynamics of reassortment among segmented viruses such as BTV.

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Razzauti, Maria, Angelina Plyusnina, Tarja Sironen, Heikki Henttonen, and Alexander Plyusnin. "Analysis of Puumala hantavirus in a bank vole population in northern Finland: evidence for co-circulation of two genetic lineages and frequent reassortment between strains." Journal of General Virology 90, no. 8 (August 1, 2009): 1923–31. http://dx.doi.org/10.1099/vir.0.011304-0.

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In this study, for the first time, two distinct genetic lineages of Puumala virus (PUUV) were found within a small sampling area and within a single host genetic lineage (Ural mtDNA) at Pallasjärvi, northern Finland. Lung tissue samples of 171 bank voles (Myodes glareolus) trapped in September 1998 were screened for the presence of PUUV nucleocapsid antigen and 25 were found to be positive. Partial sequences of the PUUV small (S), medium (M) and large (L) genome segments were recovered from these samples using RT-PCR. Phylogenetic analysis revealed two genetic groups of PUUV sequences that belonged to the Finnish and north Scandinavian lineages. This presented a unique opportunity to study inter-lineage reassortment in PUUV; indeed, 32 % of the studied bank voles appeared to carry reassortant virus genomes. Thus, the frequency of inter-lineage reassortment in PUUV was comparable to that of intra-lineage reassortment observed previously (Razzauti, M., Plyusnina, A., Henttonen, H. & Plyusnin, A. (2008). J Gen Virol 89, 1649–1660). Of six possible reassortant S/M/L combinations, only two were found at Pallasjärvi and, notably, in all reassortants, both S and L segments originated from the same genetic lineage, suggesting a non-random pattern for the reassortment. These findings are discussed in connection to PUUV evolution in Fennoscandia.

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Octaviani, Cássio Pontes, Makoto Ozawa, Shinya Yamada, Hideo Goto, and Yoshihiro Kawaoka. "High Level of Genetic Compatibility between Swine-Origin H1N1 and Highly Pathogenic Avian H5N1 Influenza Viruses." Journal of Virology 84, no. 20 (August 4, 2010): 10918–22. http://dx.doi.org/10.1128/jvi.01140-10.

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Reassortment is an important mechanism for the evolution of influenza viruses. Here, we coinfected cultured cells with the pandemic swine-origin influenza virus (S-OIV) and a contemporary H5N1 virus and found that these two viruses have high genetic compatibility. Studies of human lung cell lines indicated that some reassortants had better growth kinetics than their parental viruses. We conclude that reassortment between these two viruses can occur and could create pandemic H5N1 viruses.

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Hassan, Kareem, Timm Harder2, and Hafez M. Hafez. "Avian influenza infections in poultry farms in Egypt, a continuous challenge: Current problems related to pathogenesis, epidemiology, and diagnosis." GMPC Thesis and Opinions Platform 1, no. 1 (2021): 12–16. http://dx.doi.org/10.51585/gtop.2021.0004.

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This study's main objective was to update avian influenza (AI) epidemiological situation, including molecular characterization reassortment analysis and genotyping of circulating AI virus (AIV) subtypes in Egyptian poultry farms between 2017 and 2019. As a necessity for such work, improved diagnostic tools were developed for AIV detection. Subtype H9N2 infections were detected in 27 out of 39 examined farms and were frequently mixed with high pathogenic avian influenza (HPAI)AIV H5N8 in 22/39 farms. Next-generation and Sanger sequencing helped to define novel reassortant HPAIV H5N2 and low pathogenic avian influenza (LPAIV) H9N2 in Egypt. Systematic reassortment analysis confirmed at least seven genotypes of HPAI H5NX viruses of clade 2.3.4.4b and three genotypes of LPAIV H9N2 circulating in Egypt. Several internal genes of AIVs previously detected in wild birds in Egypt were represented in the genome of novel reassortants of both HP H5Nx and H9N2 viruses suggesting local reassortment processes.

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Lebarbenchon, Camille, Srinand Sreevatsan, Thierry Lefèvre, My Yang, Muthannan A. Ramakrishnan, Justin D. Brown, and David E. Stallknecht. "Reassortant influenza A viruses in wild duck populations: effects on viral shedding and persistence in water." Proceedings of the Royal Society B: Biological Sciences 279, no. 1744 (August 2012): 3967–75. http://dx.doi.org/10.1098/rspb.2012.1271.

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Wild ducks of the genus Anas represent the natural hosts for a large genetic diversity of influenza A viruses. In these hosts, co-infections with different virus genotypes are frequent and result in high rates of genetic reassortment. Recent genomic data have provided information regarding the pattern and frequency of these reassortant viruses in duck populations; however, potential consequences on viral shedding and maintenance in the environment have not been investigated. On the basis of full-genome sequencing, we identified five virus genotypes, in a wild duck population in northwestern Minnesota (USA), that naturally arose from genetic reassortments. We investigated the effects of influenza A virus genotype on the viral shedding pattern in Mallards ( Anas platyrhynchos ) and the duration of infectivity in water, under different temperature regimens. Overall, we found that variation in the viral genome composition of these isolates had limited effects on duration, extent and pattern of viral shedding, as well as on the reduction of infectivity in water over time. These results support that, in wild ducks, functionally equivalent gene segments could be maintained in virus populations with no fitness costs when genetic reassortments occur.

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Silva, João, Athos de Oliveira, Mariana de Almeida, Richard Kormelink, Tatsuya Nagata, and Renato Resende. "Tomato Chlorotic Spot Virus (TCSV) Putatively Incorporated a Genomic Segment of Groundnut Ringspot Virus (GRSV) Upon a Reassortment Event." Viruses 11, no. 2 (February 22, 2019): 187. http://dx.doi.org/10.3390/v11020187.

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Tomato chlorotic spot virus (TCSV) and groundnut ringspot virus (GRSV) share several genetic and biological traits. Both of them belong to the genus Tospovirus (family Peribunyaviridae), which is composed by viruses with tripartite RNA genome that infect plants and are transmitted by thrips (order Thysanoptera). Previous studies have suggested several reassortment events between these two viruses, and some speculated that they may share one of their genomic segments. To better understand the intimate evolutionary history of these two viruses, we sequenced the genomes of the first TCSV and GRSV isolates ever reported. Our analyses show that TCSV and GRSV isolates indeed share one of their genomic segments, suggesting that one of those viruses may have emerged upon a reassortment event. Based on a series of phylogenetic and nucleotide diversity analyses, we conclude that the parental genotype of the M segment of TCSV was either eliminated due to a reassortment with GRSV or it still remains to be identified.

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Falkenhagen, Alexander, Corinna Patzina-Mehling, Antje Rückner, Thomas W. Vahlenkamp, and Reimar Johne. "Generation of simian rotavirus reassortants with diverse VP4 genes using reverse genetics." Journal of General Virology 100, no. 12 (December 1, 2019): 1595–604. http://dx.doi.org/10.1099/jgv.0.001322.

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Species A rotaviruses (RVAs) are a major cause of gastroenteritis in animals and humans. Their genome consists of 11 segments of dsRNA, and reassortment events between animal and human strains can contribute to the high genetic diversity of RVAs. We used a plasmid-based reverse genetics system to investigate the reassortment potential of the genome segment encoding the viral outer capsid protein VP4, which is a major antigenic determinant, mediates viral entry and plays an important role in host cell tropism. We rescued reassortant viruses containing VP4 from porcine, bovine, bat, pheasant or chicken RVA strains in the backbone of simian strain SA11. The VP4 reassortants could be stably passaged in MA-104 cells and induced cytopathic effects. However, analysis of growth kinetics revealed marked differences in replication efficiency. Our results show that the VP4-encoding genome segment has a high reassortment potential, even between virus strains from highly divergent species. This can result in replication-competent reassortants with new genomic, growth and antigenic features.

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Shoeib, Ashraf, Daniel E. Velasquez Portocarrero, Yuhuan Wang, and Baoming Jiang. "First isolation and whole-genome characterization of a G9P[14] rotavirus strain from a diarrheic child in Egypt." Journal of General Virology 101, no. 9 (September 1, 2020): 896–901. http://dx.doi.org/10.1099/jgv.0.001455.

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An unusual group A rotavirus (RVA) strain (RVA/Human-tc/EGY/AS997/2012/G9[14]) was isolated for the first time in a faecal sample from a 6-month-old child who was hospitalized for treatment of acute gastroenteritis in Egypt in 2012. Whole-genome analysis showed that the strain AS997 had a unique genotype constellation: G9-P[14]-I2-R2-C2-M2-A11-N2-T1-E2-H1. Phylogenetic analysis indicated that the strain AS997 had the consensus P[14] genotype constellation with the G9, T1 and H1 reassortment. This suggests either a mixed gene configuration originated from a human Wa-like strain and a P[14]-containing animal virus, or that this P[14] could have been acquired via reassortment of human strains only. The study shows the possible roles of interspecies transmission and multiple reassortment events leading to the generation of novel rotavirus genotypes and underlines the importance of whole-genome characterization of rotavirus strains in surveillance studies.

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Lanahan, Matthew, Andrea Erickson, and Julie Pfeiffer. "2224 Determining if intestinal commensal bacteria enhance the frequency of reassortment of an enteric, segmented virus, reovirus." Journal of Clinical and Translational Science 2, S1 (June 2018): 9. http://dx.doi.org/10.1017/cts.2018.62.

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OBJECTIVES/SPECIFIC AIMS: The overall goal is to determine if intestinal commensal bacteria play a role in enteric virus evolution. We will use reovirus, an enteric segmented virus, to investigate specific goals. First, we will determine if specific bacterial species enhance the coinfection frequency of 2 separate strains of reovirus. Second, we will determine if the presence/absence of different bacterial species in the microbiota of mice results in different reovirus reassortment frequencies. Finally, we will discover if reassortant reovirus is present in human populations. METHODS/STUDY POPULATION: My first goal is to determine if specific bacterial species enhance the coinfection frequency of 2 strains of reovirus. In our lab, we have a panel of commensal intestinal bacterial strains, as well as a number of lab adapted bacterial strains. We will use this panel of bacteria to determine if reovirus binds to different species of bacteria using a binding assay involving radiolabeled virus. Additionally, we will determine if specific species of bacteria alter the coinfection frequency through a Flow cytometry based assay. This will involve mixing virus with bacteria, infecting cells in culture, and straining for reovirus proteins for flow cytometry. Our second goal is to determine if specific bacteria promote reassortment of reovirus in a mouse model of infection. To do this, we will use gnotobiotic techniques to create mice harboring different intestinal bacteria populations. Mice will be infected with 2 strains of reovirus, and then feces and organs will be collected. Progeny virus will be subjected to a plaque assay on 2 different types of cells. The first type of cells will be normal cells in culture in which all viable viruses will form plaques. The second will be a cell line that stably expresses siRNAs against specific reovirus segments in which only specific reassortants will form plaques. These 2 plaque assays will be used to quantify the total number of viruses present and the total number of reassortant viruses present. Additionally, SDS-PAGE and RT-PCR will be used to confirm reassortants. Our third goal is to determine if reassortant reovirus is present in infected humans. To do this, I will obtain feces from reovirus-infected children and isolate reovirus. One specific reovirus reassortant is known to propogate in dual-infected mice. I will use the plaque assay technique to determine if this reassortant is also present in humans. To determine if other reassortants are present, I will use RT-PCR and SDS-PAGE. RESULTS/ANTICIPATED RESULTS: Based on previous studies with other enteric viruses, we suspect that specific bacterial species bind reovirus strains with different efficiencies. It is likely that a number of bacterial species will promote coinfection. The bacterial strains that binds both reovirus strains at a high efficiency will likely enhance coinfection by the greatest amount. It is likely that mice harboring different bacterial populations will produce different reovirus reassortment frequencies. We predict that bacteria that enhance reovirus coinfection in vitro should also enhance reovirus reassortment in our mouse model. Therefore, mice specifically lacking bacteria that promote coinfection should have significantly lower amounts of reassortant reovirus. It will be important to control for the overall amount of replication within mice with different microbiotas, as this will affect the basal reassortment frequency. We suspect that reovirus reassortants are present in humans. Work done both in vitro and in mouse models indicates that reassortment happens at high frequencies. Additionally, one specific reassortant commonly propogates in mice due to an enhanced cellular attachment phenotype. Therefore, we predict that this reassortant also commonly emerges after coinfection and reassortment in humans. DISCUSSION/SIGNIFICANCE OF IMPACT: Segmented viruses, such as influenza and rotavirus, are important human pathogens. Viral reassortment poses a unique threat to humans, as it enables new viruses to emerge and cause pandemics or epidemics. However, little is known about what factors promote viral reassortment. This study will provide insight into a novel mechanism of segmented virus evolution.

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Heitmann, Anna, Frederic Gusmag, Martin G. Rathjens, Maurice Maurer, Kati Frankze, Sabine Schicht, Stephanie Jansen, Jonas Schmidt-Chanasit, Klaus Jung, and Stefanie C. Becker. "Mammals Preferred: Reassortment of Batai and Bunyamwera orthobunyavirus Occurs in Mammalian but Not Insect Cells." Viruses 13, no. 9 (August 27, 2021): 1702. http://dx.doi.org/10.3390/v13091702.

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Reassortment is a viral genome-segment recomposition known for many viruses, including the orthobunyaviruses. The co-infection of a host cell with two viruses of the same serogroup, such as the Bunyamwera orthobunyavirus and the Batai orthobunyavirus, can give rise to novel viruses. One example is the Ngari virus, which has caused major outbreaks of human infections in Central Africa. This study aimed to investigate the potential for reassortment of Bunyamwera orthobunyavirus and the Batai orthobunyavirus during co-infection studies and the replication properties of the reassortants in different mammalian and insect cell lines. In the co-infection studies, a Ngari-like virus reassortant and a novel reassortant virus, the Batunya virus, arose in BHK-21 cells (Mesocricetus auratus). In contrast, no reassortment was observed in the examined insect cells from Aedes aegypti (Aag2) and Aedes albopictus (U4.4 and C6/36). The growth kinetic experiments show that both reassortants are replicated to higher titers in some mammalian cell lines than the parental viruses but show impaired growth in insect cell lines.

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Wenske, E. A., S. J. Chanock, L. Krata, and B. N. Fields. "Genetic reassortment of mammalian reoviruses in mice." Journal of Virology 56, no. 2 (1985): 613–16. http://dx.doi.org/10.1128/jvi.56.2.613-616.1985.

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Villa, Mara, and Michael Lässig. "Fitness cost of reassortment in human influenza." PLOS Pathogens 13, no. 11 (November 7, 2017): e1006685. http://dx.doi.org/10.1371/journal.ppat.1006685.

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NAPOLI, DENISE. "Pandemic Flu Reassortment Could Pose New Threat." Family Practice News 40, no. 12 (July 2010): 35. http://dx.doi.org/10.1016/s0300-7073(10)70762-3.

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Klempa, Boris. "Reassortment events in the evolution of hantaviruses." Virus Genes 54, no. 5 (July 25, 2018): 638–46. http://dx.doi.org/10.1007/s11262-018-1590-z.

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Dalby, Andrew R. "Complete analysis of the H5 hemagglutinin and N8 neuraminidase phylogenetic trees reveals that the H5N8 subtype has been produced by multiple reassortment events." F1000Research 5 (October 6, 2016): 2463. http://dx.doi.org/10.12688/f1000research.9261.1.

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The analysis of the complete H5 hemagglutinin and H8 neuraminidase phylogenetic trees presented in this paper shows that the H5N8 avian influenza has been generated by multiple reassortment events. The H5N8 strain does not have a single origin and is produced when the H5 hemagglutinin and N8 neuraminidase re-assort from other H5 and N8 containing strains. While it was known that there had been a re-assortment to incorporate the Guangdong H5 hemagglutinin at the start of the Korean outbreak, the results show that there have also been multiple reassortment events amongst the non-Korean sequences.

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Grigoras, Ioana, Ana Isabel del Cueto Ginzo, Darren P. Martin, Arvind Varsani, Javier Romero, Alamdar Ch Mammadov, Irada M. Huseynova, et al. "Genome diversity and evidence of recombination and reassortment in nanoviruses from Europe." Journal of General Virology 95, no. 5 (May 1, 2014): 1178–91. http://dx.doi.org/10.1099/vir.0.063115-0.

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The recent identification of a new nanovirus, pea necrotic yellow dwarf virus, from pea in Germany prompted us to survey wild and cultivated legumes for nanovirus infections in several European countries. This led to the identification of two new nanoviruses: black medic leaf roll virus (BMLRV) and pea yellow stunt virus (PYSV), each considered a putative new species. The complete genomes of a PYSV isolate from Austria and three BMLRV isolates from Austria, Azerbaijan and Sweden were sequenced. In addition, the genomes of five isolates of faba bean necrotic yellows virus (FBNYV) from Azerbaijan and Spain and those of four faba bean necrotic stunt virus (FBNSV) isolates from Azerbaijan were completely sequenced, leading to the first identification of FBNSV occurring in Europe. Sequence analyses uncovered evolutionary relationships, extensive reassortment and potential remnants of mixed nanovirus infections, as well as intra- and intercomponent recombination events within the nanovirus genomes. In some virus isolates, diverse types of the same genome component (paralogues) were observed, a type of genome complexity not described previously for any member of the family Nanoviridae. Moreover, infectious and aphid-transmissible nanoviruses from cloned genomic DNAs of FBNYV and BMLRV were reconstituted that, for the first time, allow experimental reassortments for studying the genome functions and evolution of these nanoviruses.

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Matthijnssens, Jelle, Mustafizur Rahman, and Marc Van Ranst. "Two out of the 11 genes of an unusual human G6P[6] rotavirus isolate are of bovine origin." Journal of General Virology 89, no. 10 (October 1, 2008): 2630–35. http://dx.doi.org/10.1099/vir.0.2008/003780-0.

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In 2003, we described the first human G6P[6] rotavirus strain (B1711). To investigate further the molecular origin of this strain and to determine the possible reassortments leading to this new gene constellation, the complete genome of strain B1711 was sequenced. SimPlot analyses were conducted to compare strain B1711 with other known rotavirus gene segments, and phylogenetic dendrograms were constructed to analyse the origin of the eleven genome segments of strain B1711. Our analysis indicated that strain B1711 acquired its VP1-, VP2-, VP4-, VP6- and NSP1–5-encoding gene segments from human DS-1-like P[6] rotavirus strains, and its VP3 and VP7 gene segments from a bovine rotavirus strain through reassortment. The introduction of animal–human reassortant strains, which might arise in either of the hosts, into the human rotavirus population is an important mechanism for the generation of rotavirus diversity, and might be a challenge for the current rotavirus vaccines and vaccines under development.

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GOEDHALS, D., P. A. BESTER, J. T. PAWESKA, R. SWANEPOEL, and F. J. BURT. "Next-generation sequencing of southern African Crimean-Congo haemorrhagic fever virus isolates reveals a high frequency of M segment reassortment." Epidemiology and Infection 142, no. 9 (May 1, 2014): 1952–62. http://dx.doi.org/10.1017/s0950268814000818.

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SUMMARYCrimean Congo haemorrhagic fever virus (CCHFV) is a bunyavirus with a single-stranded RNA genome consisting of three segments (S, M, L), coding for the nucleocapsid protein, envelope glycoproteins and RNA polymerase, respectively. To date only five complete genome sequences are available from southern African isolates. Complete genome sequences were generated for 10 southern African CCHFV isolates using next-generation sequencing techniques. The maximum-likelihood method was used to generate tree topologies for 15 southern African plus 26 geographically distinct complete sequences from GenBank. M segment reassortment was identified in 10/15 southern African isolates by incongruencies in grouping compared to the S and L segments. These reassortant M segments cluster with isolates from Asia/Middle East, while the S and L segments cluster with strains from South/West Africa. The CCHFV M segment shows a high level of genetic diversity, while the S and L segments appear to co-evolve. The reason for the high frequency of M segment reassortment is not known. It has previously been suggested that M segment reassortment results in a virus with high fitness but a clear role in increased pathogenicity has yet to be shown.

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Peiris, J. S. M., Y. Guan, D. Markwell, P. Ghose, R. G. Webster, and K. F. Shortridge. "Cocirculation of Avian H9N2 and Contemporary “Human” H3N2 Influenza A Viruses in Pigs in Southeastern China: Potential for Genetic Reassortment?" Journal of Virology 75, no. 20 (October 15, 2001): 9679–86. http://dx.doi.org/10.1128/jvi.75.20.9679-9686.2001.

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ABSTRACT Pigs are permissive to both human and avian influenza viruses and have been proposed to be an intermediate host for the genesis of pandemic influenza viruses through reassortment or adaptation of avian viruses. Prospective virological surveillance carried out between March 1998 and June 2000 in Hong Kong, Special Administrative Region, People's Republic of China, on pigs imported from southeastern China, provides the first evidence of interspecies transmission of avian H9N2 viruses to pigs and documents their cocirculation with contemporary human H3N2 (A/Sydney/5/97-like, Sydney97-like) viruses. All gene segments of the porcine H9N2 viruses were closely related to viruses similar to chicken/Beijing/1/94 (H9N2), duck/Hong Kong/Y280/97 (H9N2), and the descendants of the latter virus lineage. Phylogenetic analysis suggested that repeated interspecies transmission events had occurred from the avian host to pigs. The Sydney97-like (H3N2) viruses isolated from pigs were related closely to contemporary human H3N2 viruses in all gene segments and had not undergone genetic reassortment. Cocirculation of avian H9N2 and human H3N2 viruses in pigs provides an opportunity for genetic reassortment leading to the emergence of viruses with pandemic potential.

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Lyons, Daniel, and Adam Lauring. "Mutation and Epistasis in Influenza Virus Evolution." Viruses 10, no. 8 (August 3, 2018): 407. http://dx.doi.org/10.3390/v10080407.

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Influenza remains a persistent public health challenge, because the rapid evolution of influenza viruses has led to marginal vaccine efficacy, antiviral resistance, and the annual emergence of novel strains. This evolvability is driven, in part, by the virus’s capacity to generate diversity through mutation and reassortment. Because many new traits require multiple mutations and mutations are frequently combined by reassortment, epistatic interactions between mutations play an important role in influenza virus evolution. While mutation and epistasis are fundamental to the adaptability of influenza viruses, they also constrain the evolutionary process in important ways. Here, we review recent work on mutational effects and epistasis in influenza viruses.

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Ma, Wenjun, Marie Gramer, Kurt Rossow, and Kyoung-Jin Yoon. "Isolation and Genetic Characterization of New Reassortant H3N1 Swine Influenza Virus from Pigs in the Midwestern United States." Journal of Virology 80, no. 10 (May 15, 2006): 5092–96. http://dx.doi.org/10.1128/jvi.80.10.5092-5096.2006.

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ABSTRACT Since the introduction of H3N2 swine influenza viruses (SIVs) into U.S. swine in 1998, H1N2 and H1N1 reassortant viruses have emerged from reassortment between classical H1N1 and H3N2 viruses. In 2004, a new reassortant H3N1 virus (A/Swine/Minnesota/00395/2004) was identified from coughing pigs. Phylogenetic analyses revealed a hemagglutinin segment similar to those of contemporary cluster III H3N2 SIVs and a neuraminidase sequence of contemporary H1N1 origin. The internal genes were of swine, human, and avian influenza virus origin, similar to those of contemporary U.S. cluster III H3N2 SIVs. The recovery of H3N1 is further evidence of reassortment among SIVs and justifies continuous surveillance.

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Golender, Natalia, Avi Eldar, Marcelo Ehrlich, Yevgeny Khinich, Gabriel Kenigswald, Joseph Seffi Varsano, Shachar Ertracht, et al. "Emergence of a Novel Reassortant Strain of Bluetongue Serotype 6 in Israel, 2017: Clinical Manifestations of the Disease and Molecular Characterization." Viruses 11, no. 7 (July 10, 2019): 633. http://dx.doi.org/10.3390/v11070633.

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Reassortment contributes to the evolution of RNA viruses with segmented genomes, including Bluetongue virus (BTV). Recently, co-circulation of natural and vaccine BTV variants in Europe, and their ensuing reassortment, were proposed to promote appearance of novel European BTV strains, with potential implications for pathogenicity, spread and vaccination policies. Similarly, the geographical features of the Mediterranean basin, which spans over portions of three continents, may facilitate the appearance of clinically relevant reassortants via co-circulation of BTV strains of African, Asian and European origins. In August–October 2017, BTV serotype 6 (BTV-6) was identified in young animals exhibiting classical clinical signs of Bluetongue (BT) at Israeli sheep and cattle farms. Sequencing and pairwise analysis of this Israeli BTV-6 isolate revealed the closest sequence homology of its serotype-defining Segment 2 was with that of South African reference BTV-6 strain 5011 (93.88% identity). In contrast, the other viral segments showed highest homology (97.0%–99.47% identity) with BTV-3, -4 and -9 of Mediterranean and African origins. Specifically, four viral segments were nearly identical (99.13%–99.47%), with Tunisian and Italian BTV-3 strains (TUN2016 and SAD2018, correspondingly). Together, our data suggest that Mediterranean co-circulation and reassortment of BTV-3 and BTV-6 drove the emergence of a novel and virulent BTV-6 strain

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Falkenhagen, Alexander, Corinna Patzina-Mehling, Ashish K. Gadicherla, Amy Strydom, Hester G. O’Neill, and Reimar Johne. "Generation of Simian Rotavirus Reassortants with VP4- and VP7-Encoding Genome Segments from Human Strains Circulating in Africa Using Reverse Genetics." Viruses 12, no. 2 (February 11, 2020): 201. http://dx.doi.org/10.3390/v12020201.

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Human rotavirus A (RVA) causes acute gastroenteritis in infants and young children. The broad use of two vaccines, which are based on RVA strains from Europe and North America, significantly reduced rotavirus disease burden worldwide. However, a lower vaccine effectiveness is recorded in some regions of the world, such as sub-Saharan Africa, where diverse RVA strains are circulating. Here, a plasmid-based reverse genetics system was used to generate simian RVA reassortants with VP4 and VP7 proteins derived from African human RVA strains not previously adapted to cell culture. We were able to rescue 1/3 VP4 mono-reassortants, 3/3 VP7 mono-reassortants, but no VP4/VP7 double reassortant. Electron microscopy showed typical triple-layered virus particles for the rescued reassortants. All reassortants stably replicated in MA-104 cells; however, the VP4 reassortant showed significantly slower growth compared to the simian RVA or the VP7 reassortants. The results indicate that, at least in cell culture, human VP7 has a high reassortment potential, while reassortment of human VP4 from unadapted human RVA strains with simian RVA seems to be limited. The characterized reassortants may be useful for future studies investigating replication and reassortment requirements of rotaviruses as well as for the development of next generation rotavirus vaccines.

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Journal articles on the topic 'Reassortment'

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