Auswahl der wissenschaftlichen Literatur zum Thema „Infections à Caliciviridae“

Besides noroviruses, the Caliciviridae family comprises four other accepted genera: Sapovirus, Lagovirus, Vesivirus, and Nebovirus. There are six new genera proposed: Recovirus, Valovirus, Bavovirus, Nacovirus, Minovirus, and Salovirus. All Caliciviridae have closely related genome structures, but are genetically and antigenically highly diverse and infect a wide range of mammalian host species including humans. Recombination in nature is not infrequent for most of the Caliciviridae, contributing to their diversity. Sapovirus infections cause diarrhoea in pigs, humans and other mammalian hosts. Lagovirus infections cause systemic haemorrhagic disease in rabbits and hares, and vesivirus infections lead to lung disease in cats, vesicular disease in swine, and exanthema and diseases of the reproductive system in large sea mammals. Neboviruses are an enteric pathogen of cattle, differing from bovine norovirus. At present, only a few selected caliciviruses can be propagated in cell culture (permanent cell lines or enteroids), and for most of the cultivatable caliciviruses helper virus-free, plasmid only-based reverse genetics systems have been established. The replication cycles of the caliciviruses are similar as far as they have been explored: viruses interact with a multitude of cell surface attachment factors (glycans) and co-receptors (proteins) for adsorption and penetration, use cellular membranes for the formation of replication complexes and have developed mechanisms to circumvent innate immune responses. Vaccines have been developed against lagoviruses and vesiviruses, and are under development against human noroviruses.

While recent changes in treatment have reduced the lethality of idiopathic chronic diarrhea (ICD), this condition remains one of the most common causes of rhesus macaque deaths in non-human primate research centers. We compared the viromes in fecal swabs from 52 animals with late stage ICD and 41 healthy animals. Viral metagenomics targeting virus-like particles was used to identify viruses fecally shed by each animal. Five viruses belonging to the Picornaviridae, one to the Caliciviridae, one to the Parvoviridae, and one to the Adenoviridae families were identified. The fraction of reads matching each viral species was then used to estimate and compare viral loads in ICD cases versus healthy controls. None of the viruses detected in fecal swabs were strongly associated with ICD.

Acute infectious gastroenteritis is an important illness worldwide, especially on children, with viruses accounting for approximately 70% of the acute cases. A high number of these cases have an unknown etiological agent and the rise of next generation sequencing technologies has opened new opportunities for viral pathogen detection and discovery. Viral metagenomics in routine clinical settings has the potential to identify unexpected or novel variants of viral pathogens that cause gastroenteritis. In this study, 124 samples from acute gastroenteritis patients from 2012–2014 previously tested negative for common gastroenteritis pathogens were pooled by age and analyzed by next generation sequencing (NGS) to elucidate unidentified viral infections. The most abundant sequences detected potentially associated to acute gastroenteritis were from Astroviridae and Caliciviridae families, with the detection of norovirus GIV and sapoviruses. Lower number of contigs associated to rotaviruses were detected. As expected, other viruses that may be associated to gastroenteritis but also produce persistent infections in the gut were identified including several Picornaviridae members (EV, parechoviruses, cardioviruses) and adenoviruses. According to the sequencing data, astroviruses, sapoviruses and NoV GIV should be added to the list of viral pathogens screened in routine clinical analysis.

Sapovirus of the Caliciviridae family is an important agent of acute gastroenteritis in children and piglets. The Sapovirus genus is divided into seven genogroups (G), and strains from the GIII, GVI and GVII are associated with infections in swine. Despite the high prevalence in some countries, there are no studies related to the presence of porcine enteric sapovirus infections in piglets in Brazil. In the present study, 18 fecal specimens from piglets up to 28 days were examined to determine the presence of sapovirus genome by RT-PCR assay, using primers designed to amplify a 331 bp segment of the RNA polymerase gene. In 44.4% (8/18) of fecal samples, an amplified DNA fragment was obtained. One of these fragments was sequenced and submitted to molecular and phylogenetic analysis. This analysis revealed high similarity, with nucleotides (87%) and amino acids (97.8%), to the Cowden strain, the GIII prototype of porcine enteric calicivirus. This is the first description of sapovirus in Brazilian swine herds.

HEV is responsible for large epidemics of acute hepatitis and sporadic cases in southeast and central Asia, the Middle East, parts of Africa and Mexico. Few HEV infections have been reported in non-travelers in industrialized countries, including the Netherlands. HEV infection spreads by the fecal-oral route, usually through contaminated water. The clinical illness resembles other forms of acute viral hepatitis, with onset after an incubation period of one to eight weeks. Clinical attack rates are the highest among young adults. In younger age groups, infections are more often anicteric and asymptomatic. Chronic HEV infection has not been observed. Although the death rate is usually low (0.07% to 0.6%), the illness may be particularly severe among pregnant women, with death rates as high as 25%. To date, no specific treatment is available for HEV infection. Ensuring a clean drinking water supply remains the best preventive strategy. HEV is a small, non-enveloped virus that has apositive-sense, single-stranded RNA genome of approximately 7.2 Kb. The genome contains three open reading frames (ORFs). In general, different genotypes circulate within different geographical areas, (genotype 1: Southeast and Central Asia, genotype 2: Mexico, genotype 3: USA-US1,US2 , SwUS and genotype 4: China). HEV was initially considered to be a member of the family Caliciviridae. However, on the basis of comparative phylogenetic analysis, it was recendy removed from the Caliciviridae family. In Western Europe and the United States, clinical cases of hepatitis caused by HEV are rare and most often they have been associated with travel to areas, where HEV is endemic. However, novel strains of HEV have been isolated in the US and in Europe from patients without a history of travel to regions endemic for HEV. Serological studies in industrialized countries have shown that the prevalence of anti-HEV antibodies is 1-6% among blood donors and is much higher in some populations. The cause of this relatively high prevalence of anti-HEV in countries, where clinical hepatitis E is rare, is unknown. Balayan et al. first demonstrated that domestic pigs could be experimentally infected with a human HEV isolate. Clayson et al. subsequently detected RNA and antibodies of HEV in pigs in Nepal, but the virus was not characterized. A unique swine HEV was first isolated in 1997. Later studies revealed that swine from other countries, such as Australia, Vietnam, Taiwan, Canada, Spain and Greece, were also infected with HEV. The swine HEV strain isolated from a pig in Illinois is genetically very closely related to two U.S. strains of human HEV. Similarly, the swine HEV strains isolated from pigs in Taiwan are closely related to Taiwanese strains of human HEV. Interspecies transmission of HEV has been experimentally demonstrated: swine HEV infected non-human primates and a strain of human HEV infected pigs. Also, HEV from swine might sometimes be transmitted to humans through environmental contact. These findings implicate a possible transmission of the virus from pigs to humans. These data suggested that HEV infection of humans through contact with pigs may be possible and that swine veterinarians and other pig handlers may be at risk of zoonotic infection.

The exact number of cats living on our planet is unknown, but there are reports with reference to studies conducted by French scientists from the University of Lyon (France) in 400 million domestic cats, most of which live in the United States and Brazil (93 and about 100 million. in accordance). However, according to researchers, the first place in the world in terms of the number of cats per capita is Australia (ratio of 9:10), and Ukraine is in the top 10 countries with the largest number of domestic cats. In the mid-90s of the twentieth century, Ukraine faced a new infectious disease that affects different species of the feline family - infectious feline peritonitis (IPC), the causative agent of which is a virus of the family Coronaviridae. Animal coronaviruses have been a problem for more than 50 years, however, given their variability and large diversity, the study of this group of viruses continues today. The article presents data on the epizootological features of coronavirus infection in cats for the period 2019 - 2020 in veterinary clinics in Zhytomyr and Kyiv. During a certain period of time, during the experiment, 115 samples were taken for the study, of which 95 animals were detected with the virus of the family Coronaviridae. The paper highlights the results of the study of age and breed predisposition. It has been found that 2-6 month old kittens are most prone, especially breeds such as British, Persian and Scottish. Indicators of seasonality of manifestation, and also dynamics of morbidity of cats with a coronavirus infection are resulted. In the spring and summer, the peak incidence of the studied disease was noted. According to the results of the epizootic analysis, a nosological profile of infectious diseases in cats was formed, which is represented by 8 infections, and the most frequently registered diseases are caused by viruses of the families Herpesviridae Caliciviridae and Parvoviridae.

Abstract Norovirus, a positive stranded RNA virus in the family Caliciviridae, is a major cause of acute gastroenteritis. Outbreaks occur primarily in locations such as schools, nursing homes, and cruise ships where individuals are in close proximity. An acute norovirus infection can become chronic in immunocompromised individuals, and an effective antiviral drug is needed. The 7.5 kb genome encodes a polyprotein in ORF1 that is co-translationally cleaved by the viral protease into six nonstructural proteins. The two structural proteins, VP1 and VP2, are encoded in ORF2 and ORF3, respectively. The viral proteins mediate replication and packaging of the genome into icosahedral capsids. The host cell provides additional proteins and building blocks for replication, but only a few essential host factors have been elucidated. To gain insight into the host response to norovirus infection, we performed next generation sequencing-based RNA sequencing on murine macrophages infected with murine norovirus. We obtained RNA from a time course of infection at 0, 8, 14, and 20 hours post infection with mock infections at 0 and 20 hours. Analysis of the host transcriptome reveals full activation of cellular immune response pathways, with NF-kβ, STAT1, and STAT3-based signaling evident. In addition, we observed transcriptional evidence of IRF3 activation with a transition to IRF3/IRF7 signaling. TNF-a-based activation is also clear with most downstream effectors up-regulated. These observations correlate well with the known cytokine response from patient serum samples, disease progression, and symptomatology of human norovirus. We are currently applying these findings toward drug discovery efforts.

Viruses are a major cause of acute gastroenteritis (AGE) in cats, chiefly in younger animals. Enteric specimens collected from 29 cats with acute enteritis and 33 non-diarrhoeic cats were screened in PCRs and reverse transcription (RT) PCR for a large panel of enteric viruses, including also orphan viruses of recent identification. At least one viral species, including feline panleukopenia virus (FPV), feline enteric coronavirus (FCoV), feline chaphamaparvovirus, calicivirus (vesivirus and novovirus), feline kobuvirus, feline sakobuvirus A and Lyon IARC polyomaviruses, was detected in 66.1% of the samples.. Co-infections were mainly accounted for by FPV and FCoV and were detected in 24.2% of the samples. The virome composition was further assessed in eight diarrhoeic samples, through the construction of sequencing libraries using a sequence-independent single-primer amplification (SISPA) protocol. The libraries were sequenced on Oxford Nanopore Technologies sequencing platform. A total of 41 contigs (>100 nt) were detected from seven viral families infecting mammals, included Parvoviridae, Caliciviridae, Picornaviridae, Polyomaviridae, Anelloviridae, Papillomaviridae and Paramyxoviridae, revealing a broad variety in the composition of the feline enteric virome.

Sapoviruses belonging to the genus Sapovirus within the family Caliciviridae are commonly responsible for severe acute gastroenteritis in both humans and animals. Caliciviruses are known to induce intrinsic apoptosis in vitro and in vivo, however, calicivirus-induced necroptosis remains to be fully elucidated. Here, we demonstrate that infection of porcine kidney LLC-PK cells with porcine sapovirus (PSaV) Cowden strain as a representative of caliciviruses induces receptor-interacting protein kinase 1 (RIPK1)-dependent necroptosis and acts as proviral compared to the antiviral function of PSaV-induced apoptosis. Infection of LLC-PK cells with PSaV Cowden strain showed that the interaction of phosphorylated RIPK1 (pRIPK1) with RIPK3 (pRIPK3), mixed lineage kinase domain-like protein (pMLKL) increased in a time-dependent manner, indicating induction of PSaV-induced RIPK1-dependent necroptosis. Interfering of PSaV-infected cells with each necroptotic molecule (RIPK1, RIPK3, or MLKL) by treatment with each specific chemical inhibitor or knockdown with each specific siRNA significantly reduced replication of PSaV but increased apoptosis and cell viability, implying proviral action of PSaV-induced necroptosis. In contrast, treatment of PSaV-infected cells with pan-caspase inhibitor Z-VAD-FMK increased PSaV replication and necroptosis, indicating an antiviral action of PSaV-induced apoptosis. These results suggest that PSaV-induced RIPK1-dependent necroptosis and apoptosis‒which have proviral and antiviral effects, respectively‒counterbalanced each other in virus-infected cells. Our study contributes to understanding the nature of PSaV-induced necroptosis and apoptosis and will aid in developing efficient and affordable therapies against PSaV and other calicivirus infections.

ABSTRACT Noroviruses, which are members of the Caliciviridae family, represent the leading cause of nonbacterial gastroenteritis in developed countries; such norovirus infections result in high economic costs for health protection. Person-to-person contact, contaminated water, and foods, especially raw shellfish, vegetables, and fruits, can transmit noroviruses. We inactivated feline calicivirus, a surrogate for the nonculturable norovirus, in cell culture medium and mineral water by heat and high hydrostatic pressure. Incubation at ambient pressure and 75°C for 2 min as well as treatment at 450 MPa and 15°C for 1 min inactivated more than 7 log10 PFU of calicivirus per ml in cell culture medium or mineral water. The heat and pressure time-inactivation curves obtained with the calicivirus showed tailing in the logarithmic scale. Modeling by nth-order kinetics of the virus inactivation was successful in predicting the inactivation of the infective virus particles. The developed model enables the prediction of the calicivirus reduction in response to pressures up to 500 MPa, temperatures ranging from 5 to 75°C, and various treatment times. We suggest high pressure for processing of foods to reduce the health threat posed by noroviruses.

Le norovirus, un virus non-enveloppé à ARN simple brin positif (+) de la famille des Caliciviridae est très contagieux et résistant. Un important effort de recherche est mené pour comprendre les mécanismes de la pathogenèse norovirale. Le système immunitaire inné est principalement activé lors des infections à norovirus. L'ubiquitination est un processus post-traductionnel ATP-dépendant, qui régule de nombreuses étapes de cette réponse immunitaire en catalysant l’ajout de différents types de chaînes de polyubiquitine sur certains résidus lysine de protéines cibles de manière à réguler leur sort.Il est à noter que des niveaux accrus de polyubiquitination peuvent être mesurés dans des cultures de macrophages après infection avec la souche de norovirus murin S99 (MNoV_S99). Dans une première étude, nous avons évalué comment l'altération de la formation des chaînes de polyubiquitine pouvait affecter le cycle de vie de MNoV_S99. En utilisant la lignée cellulaire de macrophage Raw264.7, plusieurs lignées cellulaires stables ont été générées en surexprimant les constructions YFP-Ubiquitin_WT, _K29R, _K48R ou_K63R. Toutes les constructions non-WT codent une protéine de fusion d'ubiquitine dont une lysine a été mutée en un résidu arginine, empêchant ainsi la formation des chaînes de polyubiquitine correspondantes. Une expression significativement réduite de plusieurs marqueurs viraux ainsi qu’une diminution significative des titres viraux a pu être mesurée seulement dans les cellules K48R. Cette régulation négative n’était pas liée à une entrée virale perturbée, mais plutôt par une hypersécrétion constitutive de la cytokine pro-inflammatoire TNF générant ainsi un environnement hostile à la propagation du MNoV_S99. L’ajout de chaînes de polyubiquitine K48 sur un substrat entraîne généralement celui-ci vers la dégradation protéasomale. Nos données sont les premières à suggérer que le MNoV_S99 bénéficie de la régulation à la baisse d’un ou plusieurs composants cytosoliques anti-viraux, encore non identifiés, vraisemblablement sensibles à la dégradation protéasomale. Les E3-ubiquitine ligases jouent un rôle central dans le processus d'ubiquitination en sélectionnant les substrats à ubiquitiner. Il a été démontré que SMURF1, une ubiquitine ligase à domaine HECT, atténue la demi-vie de plusieurs agents pathogènes par le biais de l'ubiquitination K48.Dans la seconde étude présentée dans ce manuscrit, nous avons analysé le rôle joué par SMURF1 dans la propagation du MNoV_S99. Tout d’abord, nous avons identifié l’interaction de SMURF1 avec la principale protéine de capside norovirale VP1. Mais cette interaction n'est pas associée à l'ubiquitination de la capside virale, ce qui suggère que le virus lui-même n'est pas ciblé par la dégradation protéasomale. En effet, lorsque des macrophages dérivés de la moelle osseuse (BMDM), de souris, où Smurf1 est inactivé par rapport à des souris sauvages, ont été infectés par le MNoV_S99, nous avons mesuré une diminution significative de l'expression de plusieurs marqueurs viraux. De même, les titres viraux dans les cultures Smurf1-/-étaient significativement inférieurs à ceux des BMDM WT. Ceci suggère un rôle bénéfique de SMURF1 et de l'ubiquitination K48-dépendante dans le cycle de vie des norovirus. Ceci a été confirmé par le fait que les BMDM WT traités avec l'inhibiteur de protéasome MG132 ont montré une production de MNoV_S99 significativement réduite.Dans l'ensemble, nos données permettent de mettre en lumière un rôle bénéfique de l'activité protéasomale dans le maintien d'un environnement permissif dans la propagation de la souche S99 du norovirus murin
The Norovirus, a small non-enveloped single stranded positive-sense RNA virus, that belongs to the Caliciviridae family, is highly contagious and resistant and is a major causal agent of viral gastroenteritis resulting in a high human and socioeconomic cost. Due to a lack of approved therapy options, intensive research effort is on going to better understand the mechanisms of noroviral pathogenesis.Viral entry is known to trigger signals that activate the innate immune system in order to neutralize the pathogen. Ubiquitination is an ATP-dependent multistep posttranslational process, involved in the regulation of the immune response, in which a ubiquitin moiety is added to a substrate. Interestingly, we have measured increased levels of polyubiquitination following mouse norovirus (MNoV) infection in macrophages. Different types of polyubiquitin chains can be formed on a given target’s lysine residue which determines the fate of those proteins. In a first study we have evaluated how the alteration of polyubiquitin chain formation could affect the noroviral life cycle. Using the macrophage cell line Raw264.7, several stable cell lines were generated by overexpressing YFP-Ubiquitin_WT, _K29R, _K48Ror_K63R constructs. All non-WT constructs encode a ubiquitin fusion protein with one lysine mutated into an arginine residue, thus preventing the formation of their respective polyubiquitin chains. Upon infection with the murine norovirus S99 (MNoV_S99) strain, we measured a significantly reduced expression of the viral markers VP1, NS5 and double-stranded RNA in cells where the formation of polyubiquitin chains via lysine 48 was abrogated. The TCID50 titration method further confirmed the drop of norovirus production in these cells. This negative regulation could not be explained by perturbed viral entry, however, a constitutive hypersecretion of the pro-inflammatory cytokine TNF and downstream upregulation of IκBαphosphorylation followed by NF-κB nuclear translocation was found which could potentially impose a non-permissive environment for MNoV_S99 replication and propagation.Additionally, since K48-polyubiquitin chain formation is well described to target proteins toward proteasomal degradation, our data are the first to suggest that the MNoV_S99benefits from the down regulation of unidentified cytosolic component(s) that are cleared via the proteasome.E3-ubiquitin ligases play a central role in the ubiquitination process by selecting which substrates go through ubiquitination. SMURF1, a HECT domain ubiquitin ligase, wasshown to mitigate, via K48-ubiquitination, the half-life of several pathogens. In the second study presented in this manuscript, we have investigated the role played bySMURF1 in MNoV_S99 propagation. Interestingly, we have identified that SMURF1 can bind to the main noroviral capsid protein Vp1. But this interaction was not associated with ubiquitination of the viral capsid, suggesting that the virus itself is not targeted towards proteasomal degradation. Indeed, when bone marrow derived macrophages (BMDM), established from Smurf1 knock-out mice in comparison with WT mice, were infected with MNoV_S99 we measured significantly decreased expression of several viral markers. Similarly, viral titres in Smurf1-/- cultures were significantly lower than WT BMDMs. This hints at a beneficial role of SMURF1 and K48-dependent ubiquitination in the noroviral lifecycle. This was further confirmed when WT BMDMs treated with the proteasome inhibitor MG132 showed significantly reduced MNoV_S99 production.Taken together, our data shed light on a beneficial role of the proteasomal activity in maintaining a permissive environment for the propagation of the S99 mouse norovirus strain

Les virus RHDV (Rabbit Haemorrhagic Disease Virus) et EBHSV (European Brown Hare Syndrome Virus) ont été décrits pour la première fois sur le continent européen au début des années 1980. Ces deux virus, responsables d'hépatites nécrosantes, sont capables de tuer 90% d'une population de lapins ou de lièvres en moins 48h. Ils ont été affiliés récemment à la famille des Caliciviridae. Les calicivirus possèdent un génome à ARN simple brin de polarité positive et sont composés d'une simple capside constituée d'une unique protéine structurale de 60KDa. Les protéines de capside de RHDV et EBHSV ont été exprimées dans le système baculovirus/cellules d'insecte. Les protéines de capside recombinantes produites en quantité massive ont été retrouvées dans le surnageant de culture sous la forme de pseudo-particules, présentant les mêmes caractéristiques morphologiques et antigéniques que les virions infectieux. Les particules recombinantes de RHDV utilisées dans des tests de vaccination ont conféré une protection équivalente à celle démontrée par les vaccins actuellement commercialisés. L'étude de la séroconversion des lapins vaccinés a mis en évidence le rôle clef de la réponse humorale dans la protection contre la maladie. Ces résultats ont conduit à l'élaboration d'un vaccin recombinant actuellement en cours de développement industriel. L'utilisation des particules recombinantes de RHDV et de EBHSV lors d'études comparatives, réalisées à l'aide de plusieurs anticorps monoclonaux anti-RHDV et anti-EBHSV, ont permis de caractériser les réactions antigéniques croisées entre les deux virus. Ces résultats couplés à ceux de tests de protection croisée ont permis de classer ces deux virus dans deux sérotypes du même sérogroupe au sein de la famille des Caliciviridae. Plusieurs données concernant l'assemblage des calicivirus, obtenues par l'analyse des particules recombinantes en conditions non dénaturantes, ainsi que par l'analyse des séquences peptidiques, sont discutées.

De nombreux parasites circulent dans les populations naturelles. Au sein d’un hôte, souvent pluri-infecté, ils peuvent interagir, augmentant ou réduisant le risque d’infection et les symptômes d’autres pathogènes. L’étude de ces interactions commence seulement dans les populations naturelles. Les enjeux sont cruciaux : détecter les interactions d’intérêt, estimer la probabilité de coinfection, comprendre la cocirculation des parasites. La détection des interactions sur le terrain est compliquée par la nature des données (e.g., présence-absence) et les facteurs confondants créant des associations statistiques (fausses interactions). Ce travail visait à mener une réflexion transversale sur ces interactions et le multiparasitisme, avec des applications à des données sérologiques pour 4 virus félins suivis dans des populations rurales de chats domestiques. De nouvelles méthodes de modélisation dynamique et statistique ont été développées pour prendre en compte les facteurs générant de fausses interactions (effet cumulatif de l’âge, facteurs de risque communs) et évaluer le biais des méthodes classiques. Des synergies entre 3 couples de virus félins ont été révélées. On a aussi identifié des caractéristiques comportementales et physiologiques (modes de vie, niveau de testostérone), qui, en modulant l’exposition et la sensibilité aux pathogènes, génèrent une forte hétérogénéité entre les hôtes. Enfin, une vision intégrative des systèmes hôte-parasites est indispensable pour appréhender la complexité des communautés et évaluer l’impact de la multitude d’hôtes, de parasites et d’interactions sur la coévolution, la conservation des espèces et la gestion des maladies infectieuses
Numerous parasites circulate within natural host populations. Within a host, often pluri-infected, parasites can interact, increasing or decreasing the infection risk and/or symptoms’ severity of other pathogens. Studies of such interactions only start in natural populations. Their stakes are high: detecting interactions of interest, estimating coinfection probabilities and understanding the cocirculation of parasites. The detection of interactions in the field is however complicated by the nature of data (often presence-absence) and the existence of confounding factors that can create statistical associations (false interactions). This work aimed at having a cross-cutting reflection on those interactions and on multiparasitism, with applications on a rich dataset of four feline viruses followed in rural populations of domestic cats. New dynamical and statistical modeling methods were developed to take into account factors generating false interactions (cumulative effect of age, shared risk factors) and evaluate the biases of classical methods. Synergies between three pairs of feline viruses were revealed. In addition, we identified behavioral and physiological factors (e.g., way of life, testosterone levels) that, by modulating exposition and/or susceptibility to pathogens, generate strong heterogeneity between hosts. Finally, a more integrative approach to host-parasites systems is proposed. It now appears necessary if one wants to deal with communities’ complexity and further evaluate the impact of multiple hosts, multiple parasites and their interactions on their coevolution, species conservation and infectious diseases management

This chapter deals with hepatitis E, which is the sole member of the genus Hepevirus. Higher hygiene levels in developed countries have encouraged the relative demise of this virus that is now more common in less developed countries alongside hepatitis A. Nevertheless, the virus still causes 20 million infections per year with 3 million acute illnesses. The chapter discusses the recent detection of the virus in pooled plasma products and suggests that infection in Europe is probably more frequent than previously considered as around one quarter of the UK population have antibody to the virus. The HEV was originally classified in the Caliciviridae family. But the HEV gene order is not identical to caliciviruses, and the HEV genes that can be compared are more closely related to rubella virus. The chapter mentions that HEV was reclassified as the only member of the genus Hepevirus in the new family Hepeviridae.

Norovirus are a major cause of acute gastroenteritis worldwide. Diarrheal disease is now the fourth common cause of mortality children under the age of 5 years but remain the 2nd most cause of morbidity. NoV are associated with 18% diarrheal diseases worldwide where rotavirus vaccinations has been successfully introduced. NoV has become major cause of gastroenteritis in children. NoV belong to family caliciviridae. They are non-enveloped, single stranded positive sense RNA Viruses. The genome consists of 3 Open reading frames, ORF-1 codes for non-structural protein, ORF-2 codes for major capsid protein VP1 and ORF-3 for minor capsid protein VP2. Based on sequence difference of the capsid gene (VP1), NoV have been classified in to seven genogroup GI-GVII with over 30 genotypes. Genogroups I, II, IV are associated with human infection. Despite this extensive diversity a single genotype GII.4 has been alone to be the more prevalent. Basic epidemiological disease burden data are generated from developing countries. NoV are considered fast evolving viruses and present an extensive diversity that is driven by acquisition of point mutations and recombinations. Immunity is strain or genotype specific with little or no protection conferred across genogroups. Majority of outbreaks and sporadic norovirus cases worldwide are associated with a single genotype, GII.4 which was responsible for 62% of reported NoV outbreaks in 5 continents from 2001 to 2007. GII.4 variants have been reported as major cause of global gastroenteritis pandemics starting in 1995 frequent emergence of novel GII.4 variants is known to be due to rapid evolution and antigenic variation in response to herd immunity. Novel GII.4 variants appear almost every 2 years. Recent GII.4 variant reported include Lordsdale 1996, Farmington Hills 2002, Hunter 2004, Yerseke 2006a, Den Haag 2006b, Apeldoon 2007, New Orleans 2009,most recently Sydney 2012. Detailed molecular epidemiologic investigation of NoV is associated for understanding the genetic diversity of NoV strain and emergence of novel NoV variants. However, reports have revealed that not all individuals develop symptoms and a significant proportion remains asymptomatic after NoV infections.