Academic literature on the topic 'Host-virus interplay'

Junín virus (JUNV) belongs to the Arenaviridae family and is the causative agent of Argentine hemorrhagic fever (AHF), a severe human disease endemic to agricultural areas in Argentina. At this moment, there are no effective antiviral therapeutics to battle pathogenic arenaviruses. Cumulative reports from recent years have widely provided information on cellular factors playing key roles during JUNV infection. In this review, we summarize research on host molecular determinants that intervene in the different stages of the viral life cycle: viral entry, replication, assembly and budding. Alongside, we describe JUNV tight interplay with the innate immune system. We also review the development of different reverse genetics systems and their use as tools to study JUNV biology and its close teamwork with the host. Elucidating relevant interactions of the virus with the host cell machinery is highly necessary to better understand the mechanistic basis beyond virus multiplication, disease pathogenesis and viral subversion of the immune response. Altogether, this knowledge becomes essential for identifying potential targets for the rational design of novel antiviral treatments to combat JUNV as well as other pathogenic arenaviruses.

Cigarette smoking has been shown to increase the risk of respiratory infection, resulting in the exacerbation of infectious disease outcomes. Influenza viruses are a major respiratory viral pathogen, which are responsible for yearly epidemics that result in between 20,000 and 50,000 deaths in the US alone. However, there are limited general summaries on the impact of cigarette smoking on influenza pathogenic outcomes. Here, we will provide a systematic summarization of the current understanding of the interplay of smoking and influenza viral infection with a focus on examining how cigarette smoking affects innate and adaptive immune responses, inflammation levels, tissues that contribute to systemic chronic inflammation, and how this affects influenza A virus (IAV) disease outcomes. This summarization will: (1) help to clarify the conflict in the reports on viral pathogenicity; (2) fill knowledge gaps regarding critical anti-viral defenses such as antibody responses to IAV; and (3) provide an updated understanding of the underlying mechanism behind how cigarette smoking influences IAV pathogenicity.

Influenza is an annual epidemic and an occasional pandemic caused by pathogens that are responsible for infectious respiratory disease. Humans are highly susceptible to the infection mediated by influenza A viruses (IAV). The entry of the virus is mediated by the influenza virus hemagglutinin (HA) glycoprotein that binds to the cellular sialic acid receptors and facilitates the fusion of the viral membrane with the endosomal membrane. During IAV infection, virus-derived pathogen-associated molecular patterns (PAMPs) are recognized by host intracellular specific sensors including toll-like receptors (TLRs), C-type lectin receptors, retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs), and nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) either on the cell surface or intracellularly in endosomes. Herein, we comprehensively review the current knowledge available on the entry of the influenza virus into host cells and the molecular details of the influenza virus–host interface. We also highlight certain strategies for the development of universal influenza vaccines.

Flaviviruses are important emerging and re-emerging arthropod-borne pathogens that cause significant morbidity and mortality in humans. It consists of globally distributed human pathogens such as tick-borne encephalitis virus (TBEV), West Nile virus (WNV), Japanese encephalitis virus (JEV), yellow fever virus (YFV), dengue virus (DENV), and Zika virus (ZIKV). Depending on type, flaviviruses can cause a variety of symptoms ranging from haemorrhage to neurological disorders. Virus infection is detected by host pattern recognition receptors (PRRs), and through downstream signalling it leads to the production of interferons (IFNs). These IFNs then act in an autocrine or paracrine manner on the cells to induce various IFN-stimulated genes (ISGs), which have antiviral roles. However, the amount of IFN produced depends on the nature of the PRRs used by host cells to detect a particular virus. Although there are many PRRs present in the host cells, their relative contribution in different cell types and against a specific virus may vary. In the first study, we determined the importance of IPS-1 signalling in immunity and pathogenicity of tick-borne flaviviruses. This is an adaptor protein for cytoplasmic RIG-I-like receptors. Using IPS-1-deficient mice, we showed its importance against TBEV and Langat virus (LGTV) infection (the LGTV model virus belongs to the TBEV serogroup). Absence of IPS-1 leads to uncontrolled virus replication in the central nervous system (CNS), but it has only a minor role in shaping the humoral immune response at the periphery. LGTV-infected IPS-1-deficient mice showed apoptosis, activation of microglia and astrocytes, an elevated proinflammatory response, and recruitment of immune cells to the CNS. Interestingly, we also found that IFN-b upregulation after viral infection was dependent on IPS-1 in the olfactory bulb of the brain.  Thus, our results suggest that local immune microenvironment of distinct brain regions is critical for determination of virus permissiveness. Interferons can upregulate several ISGs. Viperin is one such ISG that has a broad-spectrum antiviral action against many viruses. However, the importance of cell type and the significance of viperin in controlling many flavivirus infections in vivo is not known. Using viperin-deficient mice, we found that viperin was necessary for restriction of LGTV replication in the olfactory bulb and cerebrum, but not in the cerebellum. This finding was also confirmed with primary neurons derived from these brain regions. Furthermore, we could also show the particular importance of viperin in cortical neurons against TBEV, WNV, and ZIKV infection. The results suggested that a single ISG can shape the susceptibility and immune response to a flavivirus in different regions of the brain. Although viperin is such an important ISG against flaviviruses, the exact molecular mechanism of action is not known. To understand the mechanism, we performed co-immunoprecipitation screening to identify TBEV proteins that could interact with viperin. While viperin interacted with the prM, E, NS2A, NS2B, and NS3 proteins of TBEV, its interaction with NS3 led to its degradation through the proteosomal pathway. Furthermore, viperin could reduce the stability of other viperin-binding TBEV proteins in an NS3-dependent manner. We screened for viperin activity regarding interaction with NS3 proteins of other flaviviruses. Viperin interacted with NS3 of JEV, ZIKV, and YFV, but selectively degraded NS3 proteins of TBEV and ZIKV, and this activity correlated with its antiviral activity against these viruses. The last study was based on in vivo characterization of the newly isolated MucAr HB 171/11 strain of TBEV which caused unusual gastrointestinal and constitutional symptoms. This strain was compared with another strain, Torö-2003, of the same European subtype of TBEV but isolated from the different focus. Here we found unique differences in their neuroinvasiveness and neurovirulence, and in the immune response to these two strains. In summary, my work shed some light on the interplay between tick-borne flavivirus and the innate immune system. I have shown two examples of CNS region-specific differences in innate immune response regarding both in IFN induction pathways and antiviral effectors. Furthermore, we have investigated the in vivo pathogenesis of a strain of TBEV that caused unusual gastrointestinal and constitutional symptoms.
Flavivirus finns spridda över hela världen och orsakar miljontals infektioner varje år. Några av de medicinsk mest viktiga flavivirusen är fästingburen encefalit virus (TBEV), West Nile virus (WNV), Japansk encefalit virus (JEV), gula febern (YFV) och Zika virus (ZIKV). Dessa virus kan orsaka olika komplikationer till exempel blödarfeber och hjärninflammation. Vid en infektion så upptäcker värdcellen virusinfektionen med hjälp av speciella receptorer, så kallade PRRs. Dessa finns i alla celler och känner igen viruskomponenter som normalt inte finns i en oinfekterad cell. När PRRs detekterar en virusinfektion svarar cellen med att tillverka ett signal protein interferon (IFN). IFN skickas ut ur cellen och hämmar virusinfektioner genom att sätta igång ett försvarsprogram i andra celler bestående av hundratals försvarsproteiner som kan motverka virusinfektionen. Vilka PRRs som behövs för att detektera ett virus är olika vid olika virusinfektioner. I första studien fann vi att IPS-1 är av yttersta vikt för skydda mot fästingburna flavivirus. IPS-1 är ett så kallat adapter protein som behövs för att två PRRs, RIG-I och MDA-5, ska kunna förmedla signaler som leder till IFN tillverkning. Med hjälp av möss som saknar IPS-1 fann vi att IPS-1 behövs för att tillverka IFN protein och skydda mot fästingburna flavivirus. IPS-1 var särskilt viktigt för interferon produktion inom luktloben i hjärnan. Därför kunde vi dra slutsatsen att immunresponsen regleras olika inom olika delar av hjärnan. Ett försvarsprotein som visat sig vara särskilt viktig vid virusinfektion är viperin. Viperin har visat sig kunna hämma en rad olika virus men den specifika rollen av viperin in vivo vid flavivirus infektion var inte fullt känd. Vi fann att viperin behövs för att hämma LGTV i lukloben och storhjärnan men inte i lillhjärnan. Vi kunde bekräfta detta med hjälp av primära nervceller isolerade från dessa hjärnregioner. Vi fann även att viperin var av yttersta vikt för att kontrollera TBEV, WNV och ZIKV infektion i nervceller från hjärnbarken (del av storhjärnan). Därför kunde vi dra slutsatsen att ett enskilt försvarsprotein kan avgöra mottagligheten mot flavivirus inom olika hjärnregioner. Trots att viperin är så viktig för att skydda mot flavivirus så vet vi inte hur viperin åstadkommer detta. Därför ville vi undersöka hur viperin kan förmedla sin antivirala effekt. Vi fann att viperin kan binda till flera TBEV proteiner, men att viperin specifikt kan bryta ner ett virusprotein som heter NS3. NS3 är väldigt viktigt för att flavivirus ska kunna etablera en infektion och kunna föröka sig. Eftersom vi visste att viperin kan hämma andra flavivirus ville vi veta om viperin även förstör NS3 från JEV, ZIKV och YFV. Vi upptäckte att viperin kunde binda till NS3 hos alla dessa flavivirus men att viperin specifikt förstörde TBEV och ZIKV NS3, intressant nog så kunde viperin endast hämma dessa virus infektioner men inte JEV och YFV. I den sista studien ville vi karaktärisera en ny TBEV stam som bara orsakar magoch tarmbesvär men inga neurologiska symptom. TBEV har aldrig tidigare visat sig kunna orsaka detta och därför ville vi undersöka saken vidare. Vi fann att denna TBEV stam skiljde sig mot en närbesläktad stam genom att orsaka en starkare immunrespons men mildare sjukdomsförlopp. Sammanfattningsvis har jag undersökt samspelet mellan fästingburna flavivirus och det medfödda immunförsvaret. Jag har även visat att immunresponsen regleras olika inom olika hjärnregioner, både beträffande IFN inducering och antivirala proteiner. Vidare har jag hittat mekanismen för hur viperin proteinet hämmar TBEV och ZIKV, vilket var genom att förstöra NS3. Dessutom har jag karaktäriserat sjukdomsförloppet hos möss efter infektion med en ovanlig TBEV stam som orsakar mag och tarm besvär.

Les mécanismes de dégradation de l'ARN représentent un processus cellulaire central. En effet, ils contrôlent la stabilité et la qualité de l'ARN et, par conséquent, régulent l'expression des gènes. D’une part, la régulation de la stabilité des transcrits est un élément essentiel au maintien de l’homéostasie cellulaire mais aussi à l’établissement d’une réponse cellulaire adaptée en cas d’infection virale. D’autre part, le succès de l’infection virale dépend fortement de la capacité du virus à prendre le contrôle des machineries d’expression géniques cellulaires. De ce fait, les virus doivent interagir avec les machineries cellulaires de dégradation de l’ARN afin de contrôler à la fois, l’expression des gènes cellulaires, et celle des gènes viraux. De nombreuses études rapportent l’existence d’une interface majeure d’interaction entre les machineries eucaryotes de dégradation de l’ARN et les protéines virales. Les virus ont non seulement la capacité d’échapper aux voies cellulaires de dégradation, mais ils peuvent également manipuler ces mécanismes cellulaires de dégradation de l’ARN afin de promouvoir leur propre réplication.Les virus influenza de type A (IAV) sont des agents pathogènes majeurs responsables d'épidémies annuelles et de pandémies occasionnelles. Pour leur cycle de réplication, les IAV dépendent de nombreuses protéines cellulaires et établissent ainsi un vaste et complexe réseau d’interactions avec le protéome cellulaire. Par ailleurs, plusieurs études rapportent l’existence de liens étroits entre les IAV et les machineries de dégradation de l’ARN. Ainsi, identifier les interactions mises en jeu lors du cycle viral participe à une meilleure compréhension du cycle viral, nécessaire au développement de stratégies antivirales. Nous avons recherché des interactions entre les protéines virales impliquées dans la réplication des IAV et un ensemble de 75 protéines cellulaires portant des activités exoribonucléases et/ou associées aux mécanismes de dégradation de l'ARN. Au total, 18 protéines ont été identifiées comme interagissant avec au moins une des protéines virales testées. Par ailleurs, l'analyse du réseau d'interaction a mis en évidence un ciblage spécifique et préférentiel des voies de dégradation de l'ARN par les protéines des IAV. Enfin, parmi les interacteurs validés, un criblage par ARN interférence a identifié neuf facteurs comme étant nécessaires à la multiplication virale.Nous avons choisi de nous concentrer sur l’exoribonucléase 1 (ERI1), identifiée comme interacteur de plusieurs composants des RNPv (RiboNucleoProtéine virale) (PB2, PB1 et NP). ERI1, via ses différents rôles dans l’homéostasie des petits ARN régulateurs, dans la maturation des ARN ribosomiques ou dans la maturation et la dégradation des ARNm histones possède un rôle central dans le contrôle de l’expression génique. En explorant l’interaction entre ERI1 et les protéines virales au cours de l’infection, nous avons mis en évidence que i) ERI1 favorise la transcription virale et que, pour ce faire, ses deux activités - liaison à l’ARN et exonucléase - sont nécessaires, ii) ERI1 interagit avec les protéines virales de manière dépendante de l’ARN, iii) ERI1 interagit avec les RNPv, iv) les protéines virales interagissent avec une forme d'ERI1 associée aux ARNm histones. Ainsi, nos données tendent vers un modèle dans lequel ERI1 associée aux ARNm histones est cooptée par la polymérase virale en transcription, favorisant ainsi la multiplication des IAV par un mécanisme qui reste cependant encore à déterminer. Ainsi, le ciblage de ERI1 par les IAV représente un autre exemple du détournement des machineries de dégradation de l’ARN par les virus, visant à créer un environnement cellulaire favorable à la réplication virale
RNA decay is a central cellular process as it regulates RNA stability and quality and thereby gene expression, which is essential to ensure proper cellular physiology and establishment of adapted responses to viral infection. Global takeover of gene expression machineries and rewiring of the cellular environment is key to the success of viral infection. Cellular proteome and viral replication are tightly connected and cellular RNA processing, stability, quality and decay accordingly influence the fate of the viral cycle. Growing evidence points towards the existence of a large interplay between eukaryotic RNA turnover machineries and viral proteins. Viruses not only evolved mechanisms to evade those RNA degradation pathways, but they also manipulate them to promote viral replication.Influenza A viruses (IAV) are major pathogens responsible for yearly epidemics and occasional pandemics. To complete their viral cycle, IAVs rely on many cellular proteins and establish a complex and highly coordinated interplay with the host proteome. Growing evidence supports the existence of a complex interplay between IAV viral proteins and RNA decay machineries. Unraveling such interplay is therefore essential to gain a better understanding of the IAV life cycle, required for the development of antiviral strategies. This led us to systematically screen interactions between viral proteins involved in IAV replication and a selected set of 75 cellular proteins carrying exoribonucleases activities or associated with RNA decay machineries. A total of 18 proteins were identified as interactors of at least one viral protein tested. Analysis of the interaction network highlighted a specific and preferential targeting of RNA degradation pathways by IAV proteins. Among validated interactors, a targeted RNAi screen identified nine factors as required for viral multiplication. We chose to focus on the 3’-5’ exoribonuclease 1 (ERI1), found in our screen as an interactor of several components of the vRNPs (viral RiboNucleoProtein) (PB2, PB1 and NP). The ERI1 protein is a major player in the control of cellular gene expression as it is essential for the maturation and decay of histone mRNA, maturation of 5.8S rRNA and miRNA homeostasis in mammalian cells. Exploring the interplay between ERI1 and viral proteins during the course of IAV infection we found that i) ERI1 promotes viral transcription, and both of its activities – RNA binding and exonuclease – are required, ii) ERI1 interacts with viral proteins in an RNA dependent manner, iii) ERI1 interacts with the transcribing vRNPs, iv) viral proteins interact with a form of ERI1 that is associated to histone mRNA. Ultimately, our data point to a model where ERI1 associated to histone mRNA is co-opted by the transcribing viral polymerase, thereby promoting IAV multiplication, through a mechanism that remains to be precisely determined. Targeting of ERI1 by IAV is another example further supporting the intricate interplay between IAV and RNA decay machineries, used to rewire cellular gene expression in order to create a favorable environment for viral replication

Els cossos de processament (cossos-P) són grànuls discrets i dinàmics que contenen mRNAs represos en la traducció així com proteïnes involucrades en la degradació dels mRNAs i de la maquinària dels miRNAs. Alguns components dels cossos-P, com els repressors de la traducció PatL1, LSm1 i DDX6, promouen la traducció i la replicació del virus de la hepatitis C (VHC) i d’altres virus RNA de polaritat positiva [RNA(+)]. A més a més, un genome wide screening en llevat va determinar que l’exonucleasa Xrn1, que també es localitza als cossos-P, pot afectar la taxa de recombinació d’un virus RNA(+) de plantes Així doncs, els components dels cossos-P estan estretament relacionats amb els cicles vitals dels virus RNA(+). En l’estudi que aquí es presenta hem explorat la relació del VHC amb els cossos-P, demostrant que la infecció pel VHC promou canvis en la composició dels cossos-P a través de l’alteració de la localització d’aquells components que són necessaris per a la replicació viral. A més a més, hem demostrat que els components dels cossos-P però no els grànuls per se són necessaris per a la replicació del VHC. Addicionalment, hem posat a punt un sistema de detecció de recombinació en cultiu cel•lular basat en replicons del VHC que permet analitzar successos de recombinació i caracteritzar la possible participació dels components dels cossos-P en aquest mecanisme d’evolució. Amb aquest sistema s’han establert les primeres estimacions en la freqüència de recombinació del VHC indicant que la recombinació en aquest virus no és gaire comú. A més a més, la reducció del nivell d’expressió de Xrn1 no va alterar la taxa de recombinació del VHC indicant que la utilització de l’exonucleasa no és una característica general en la recombinació dels virus RNA(+). En conjunt, aquests resultats incrementen el nostre coneixement sobre els aspectes bàsics de la biologia del VHC així com de l’estreta relació que aquest virus estableix amb l’hoste.

Viruses, such as the influenza A virus (IAV), are the causative agent for most of the annual respiratory epidemics in humans, and they take control of the host cell machinery and establish precise interactions with cellular components in order to propagate. The fundamental reason why viruses need living cells to multiply, is because they lack key elements that are needed for replication such as transfer ribonucleic acids (tRNAs). IAV has been shown to specifically manipulate the host-cell tRNA population to enable the efficient translation of viral proteins. tRNAs are modified, post-transcriptionally, by tRNA-modifying enzymes (TMEs) to ensure their stability and efficient translation. The majority of these modifications occurs at the wobble position, located at the anticodon loop, although they may also happen in other areas of the tRNA structure. In this study we aimed to determine whether IAV infection leads to changes in the expression of the genes that code for the TMEs. Our results demonstrated that particular genes (ELP1, ELP3, ELP6, ALKBH8 and TRMT2A) were overexpressed two hours post-infection while no striking changes were detected in other time points. We also aimed to determine whether the lack of ELP3 would influence the viral particle production by the infected cells. Using ELP3 knockout cells, our preliminary results show that the absence of this TME notably reduces viral production, suggesting a relevant role for ELP3 on the IAV life-cycle.
Os vírus, como por exemplo o vírus da influenza A (VIA), são os agentes causadores da maior parte das epidemias respiratórias anuais em seres humanos: apoderam-se e controlam a maquinaria das células hospedeiras e estabelecem interações precisas com múltiplos componentes celulares, a fim de se propagarem. A razão fundamental pela qual os vírus precisam de células vivas para se multiplicarem, é o facto de não possuírem componentes fundamentais necessários para a replicação, como por exemplo, os ácidos ribonucleicos de transferência (ARNt). Alguns estudos demonstraram que o VIA manipula as populações de ARNt de células hospedeiras de forma a induzir a tradução eficiente de proteínas virais. Os ARNt são modificados, pós-transcrição, por enzimas modificadoras de ARNt (EMTs) de forma a garantir a estabilidade dos ARNt e que a tradução ocorra da forma mais eficiente possível. A maioria dessas modificações ocorre na posição 34 dos ARNt, localizada no anti codão, embora essas modificações também ocorram em outras áreas da estrutura dos ARNt. Neste estudo, procurámos determinar se a infeção pelo VIA levava a alterações na expressão dos genes que codificam para as EMTs. Os resultados obtidos demonstraram que alguns genes (ELP1, ELP3, ELP6, ALKBH8 e TRMT2A) estavam a ser sobre-expressos duas horas após a infeção, enquanto nenhuma outra mudança significativa foi detetada em outros momentos. Para além disso procurámos também determinar se a falta de ELP3 influenciaria de alguma forma a produção de partículas virais pelas células infetadas. Resultados preliminares obtidos usando células knockout para ELP3, indicam que a ausência dessa enzima reduz notavelmente a produção viral, sugerindo um papel relevante para a ELP3 no ciclo de vida do VIA.
Mestrado em Biomedicina Molecular

The human immunodeficiency virus (HIV) infection epidemic has particularly affected the poorest regions of the world. HIV can directly or indirectly affect different aspects of renal function, and results in a variable expression of kidney disease.Acute kidney injury (AKI) occurs in approximately 20% of hospitalized patients. The prevalence of chronic kidney disease (CKD) amongst HIV-infected patients is reported at 3.5–38% in different regions of the world. The complex interplay between the pheno- and/or genotypic variants of the virus, the genetic make-up of the host, and environmental factors determine the clinical manifestations of renal disease. The association of APOL1 gene variants G1 and G2 with the risk of focal segmental glomerulosclerosis explains the high frequency of HIV-associated nephropathy (HIVAN) in populations of black ethnicity.Anti-retroviral therapy (ART) is effective in preventing progression of HIVAN. Some of the drugs used in ART regimens are potentially nephrotoxic and require dose adjustment or even avoidance in CKD. Progression to end-stage renal disease (ESRD) in HIVAN has been reported to correlate with the extent of chronic damage quantified by renal biopsy.HIV-infected patients requiring dialysis, who are stable on ART, are achieving survival rates comparable to those of non-HIV dialysis populations. Similarly, HIV infection does not seem to adversely affect patient and graft survival rates after kidney transplantation, and there has been no increase in the prevalence of opportunistic infections in transplant recipients on effective ART.

The progression of acute HCV infection to chronic disease and subsequent extrahepatic comorbidities involve both viruses and host cellular proteins interactions as well as insurrection or subjection of cell signaling and metabolic pathways in infected cells. This interaction between host-specific factors and the hepatitis C genome also weakens or impairs other physiological or metabolic regulatory roles of the hepatocytes. Several host cell proteins promote hepatitis C infection through binding to HCV nonstructural proteins (e.g., PPP2R5D). Some studies also found cytokine (e.g., IL-10, IL-6, TNF-α, and TGF-β1) gene polymorphisms to be highly associated with chronic hepatitis C (CHC) infection progression, whereas, polymorphism in some host genes (e.g., PNPLA3, ADAR-1, and IFIH1) are found to be actively involved in the induction of advanced liver fibrosis in patients co-infected with HIV-1/HCV. Host lipid metabolism reprogramming through host lipid regulators (e.g., ANGPTL-3 and 4) is also considered essential for CHC progression to severe liver disease (e.g., cirrhosis and HCC). Several microRNAs (e.g., miR-122, miR135a) are supposed to be key mediators of HCV infection progression and development of HCC in infected individuals and associated hepatic comorbidities. In chapter 1, we have illustrated the potential roles of virus-specific proteins in HCV molecular pathogenesis. Herein, we will elucidate the host-specific culprits that subvert, impede or disrupt host cells' communications, cell signaling, and metabolic pathways to propagate HCV infection. We will also elaborate that how the subversion of infected host-cell signaling and metabolic pathways disrupt cellular networks to evolve advanced fibrosis and hepatocarcinogenesis in HCV-infected individuals.

Hepatitis C virus (HCV) interaction with host cells is pivotal for natural disease course starting from asymptomatic acute infection to progress into persistent chronic infection and subsequent extrahepatic manifestations, including fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). The HCV infection biology in infected host cells via virus attachment, virus genome replication, mRNA translation, new virion formation, and egress from infected cells involves highly coordinated participation of the virus- and host-specific proteins, a plethora of genes, and cell signaling cascade. The progression of persistent chronic hepatitis C (CHC) infection to hepatic fibrosis, cirrhosis, and HCC involves viral invasion strategies against host immune system defense mechanisms as well as impeding healthy metabolic and signaling networks of the liver cells. Thereby, HCV-induced liver injury via chronic inflammatory processes that fail to resolve is responsible for decompensated cirrhosis and on occasion, hepatocarcinogenesis in infected individuals. With the latest advancement and rapid expansion of our knowledge in hepatology, the human liver is deciphered as an immunologically distinct organ with its specialized physiological niche. The relationship between human hepatocytes and different components of the immune system is quite complex and dynamic. The immunopathogenesis of various viral infections demonstrates that the immune system plays an essential role to determine the progression of many hepatic diseases through immune cell communication and cell signaling networks. In this book chapter, we overview HCV host interactions and their intricate interplay with complex crosstalk to propagate less fetal acute HCV infection to CHC and subsequent hepatocarcinogenesis (i.e. HCC) in infected individuals.

Human cytomegalovirus (HCMV) retinitis accounts for 70% of herpesvirus-infected ocular diseases. Recent advances in knowledge of innate immune responses to viral infections have elucidated a complex network of the interplay between the invading virus, the target cells, and the host immune responses. Ocular cytomegalovirus latency exacerbates the development of choroidal neovascularization. Viruses have various strategies to evade or delay the cytokine response, and buy time to replicate in the host. Some signaling proteins impact the virologic, immunologic, and pathological processes of herpesvirus infection with particular emphasis on retinitis caused by HCMV. The accumulated data suggest that signaling proteins can differentially affect the severity of viral diseases in a highly cell-type-specific manner, reflecting the diversity and complexity of herpesvirus infection and the ocular compartment. By summarizing the immunological characteristics and pathogenesis of HCMV ocular infection, it will provide important information on the development of antiviral therapy, immunotherapy, and antidrug resistance.

The ability of a new vaccine design based on control the intracellular physiological consequences of both the electrical properties and the electromagnetic radiation interactions between a virus and a host cell, which is a method to strengthen immune system develop protection against COVID-19 and new strains. The capacity of COVID-19 to bind to angiotensin-converting enzyme 2 (ACE2) and immune evasion mechanisms are only one of the properties required to stimulate a preventative immune response. In this chapter, a multidimensional new strategy is used to exemplify the empowerment function intracellular and extracellular level information can play in the support of immunogen against COVID-19 pathogens. Besides during this chapter, the nature of electromagnetic radiation is described as a vibrating string based on a string-theory and unification of electromagnetic radiation and gravitational waves by supporting with multiple cites strong evidence. Overall, we demonstrate a new approach to understand the important role of the physiological consequences of the interplay between the immune system and COVID-19 and designing vaccine strategy immunogens that take advantage of that information against COVID-19 and new strains.

The complex interplay between host and EBV has made it difficult to elaborate useful vaccines protecting against EBV diseases. It is encouraging to see that EBV vaccine programs have started to incorporate different arms of the immune system. An array of argument calls for a realistic goal for vaccine strategies which should be preventing EBV diseases, rather than EBV infection. EBV is the primary cause of infectious mononucleosis and is associated with epithelial cell carcinomas, as well as lymphoid malignancies. Parallel to this need, one could propose priorities for future research: (i) identification of surrogate predictive markers for the development of EBV diseases (ii) determination of immune correlates of protection in animal models and humans.