Arenavirus Evasion of Host Anti-Viral Responses

Hayes, Melissa; Salvato, María S.

doi:10.3390/v4102182

Cited by 13 publications

(11 citation statements)

References 50 publications

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“…Infection of rhesus macaques by the OW LCMV WE strain results in a fatal, Lassa fever-like disease, while the LCMV Arm strain does not induce disease. Interestingly, the LCMV WE strain also inhibited LCMV Arm-induced Toll-like receptor 2 (TLR2)/ Mal-dependent cytokine production in similar coinfection studies (47,48).…”

Section: Discussionmentioning

confidence: 76%

Highly Pathogenic New World and Old World Human Arenaviruses Induce Distinct Interferon Responses in Human Cells

Huang

Kolokoltsova

Yun

et al. 2015

J Virol

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The arenavirus family includes several important pathogens that cause severe and sometimes fatal diseases in humans. The highly pathogenic Old World (OW) arenavirus Lassa fever virus (LASV) is the causative agent of Lassa fever (LF) disease in humans. LASV infections in severe cases are generally immunosuppressive without stimulating interferon (IFN) induction, a proinflammatory response, or T cell activation. However, the host innate immune responses to highly pathogenic New World (NW) arenaviruses are not well understood. We have previously shown that the highly pathogenic NW arenavirus, Junin virus (JUNV), induced an IFN response in human A549 cells. Here, we report that Machupo virus (MACV), another highly pathogenic NW arenavirus, also induces an IFN response. Importantly, both pathogenic NW arenaviruses, in contrast to the OW highly pathogenic arenavirus LASV, readily elicited an IFN response in human primary dendritic cells and A549 cells. Coinfection experiments revealed that LASV could potently inhibit MACV-activated IFN responses even at 6 h after MACV infection, while the replication levels of MACV and LASV were not affected by virus coinfection. Our results clearly demonstrated that although all viruses studied herein are highly pathogenic to humans, the host IFN responses toward infections with the NW arenaviruses JUNV and MACV are quite different from responses to infections with the OW arenavirus LASV, a discovery that needs to be further investigated in relevant animal models. This finding might help us better understand various interplays between the host immune system and highly pathogenic arenaviruses as well as distinct mechanisms underlying viral pathogenesis.

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Section: Discussionmentioning

confidence: 76%

Highly Pathogenic New World and Old World Human Arenaviruses Induce Distinct Interferon Responses in Human Cells

Huang

Kolokoltsova

Yun

et al. 2015

J Virol

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“…P2 increases DNA binding of the activating RelA/p50 dimer of NF-κB, whereas P18 increases DNA binding of the repressive p50/p50 homodimeric form [136]. A similar mechanism was reported for suppression of IL-8 or IL-6 expression in cultured cells by virulent but not attenuated arenaviruses [137]. Meta-analyses of profiling studies in several laboratories identified transcription factors that were shared among some of the virulent infections.…”

Section: Profiling Disease Progressionmentioning

confidence: 90%

“…However, there was a minor disagreement in their results: for one group [189], DCs incubated with both infectious and inactivated LASV produced IL-1β, IL-8, little IL-10 and no TNF-α and for the other group [47], both DCs and MPs incubated with infectious LASV suppressed TNF-α, IL-1β and IL-10 while inactivated virus particles fostered production of those chemokines. The Lyon group concluded that the LASV stock of the Atlanta group ‘probably contained a significant quantity of noninfectious viral products [47],’ implying that replication of infectious particles is needed to suppress innate immunity, a finding later corroborated by others [137]. Two findings in human beings with LF lent weight to the idea that innate immunity is suppressed in severe infection: first, fatal cases of LHF had lower chemokine levels (IL-8 and IP-10) compared with survivors [166] and, second, IL-8 was the only cytokine that peaked in infected contacts of severe LASV cases who did not develop LF disease [71].…”

Section: Conclusion: the Importance Of Early Immune Responsementioning

confidence: 94%

“…In the comparisons of attenuated and pathogenic arenaviruses, differences in gene expression do not reflect differences in replication potential of the viruses but rather the fact that the pathogenic viruses suppress innate immunity, allowing higher levels of virus production, so the high viremia triggers an inflammatory response that contributes to disease [137,141]. Both the pathogenic and nonpathogenic infections upregulate ISGs, but since viremia is more sustained for the pathogenic virus, sustained ISG expression becomes a biomarker of severe disease.…”

Section: Profiling Disease Progressionmentioning

confidence: 99%

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Genomic Profiling of Host Responses to Lassa Virus: Therapeutic Potential from Primate to Man

Zapata

Salvato

2015

Future Virol.

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Lassa virus infection elicits distinctive changes in host gene expression and metabolism. We focus on changes in host gene expression that may be biomarkers that discriminate individual pathogens or may help to provide a prognosis for disease. In addition to assessing mRNA changes, functional studies are also needed to discriminate causes of disease from mechanisms of host resistance. Host responses that drive pathogenesis are likely to be targets for prevention or therapy. Host responses to Lassa or its related arenaviruses have been monitored in cell culture, in animal models of hemorrhagic fever, in Lassa-infected nonhuman primates and, to a limited extent, in infected human beings. Here, we describe results from those studies and discuss potential targets for reducing virus replication and mitigating disease.

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“…Also, a calculated score was provided as a measure of the degree of binding interaction [57]. Toll-like receptor-2 (TLR2) can mediate high proinflammatory responses against LASV infection [58]. Therefore, TLR2 structure was used as the receptor (PDB ID: 3A7B) and the refined vaccine protein as the ligand [59].…”

Section: Molecular Docking Between the Vaccine And Tlr2 Receptormentioning

confidence: 99%

Immunoinformatics-Guided Designing of Peptide Vaccine against Lassa Virus with Dynamic and Immune Simulation Studies

S¹,

Nain²,

F³

et al. 2019

Preprint

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Lassa virus (LASV) is responsible for a type of acute viral haemorrhagic fever referred to as Lassa fever. Lack of adequate treatment and preventive measures against LASV resulted in a high mortality rate in its endemic regions. In this study, a multi-epitope vaccine was designed using immunoinformatics as a prophylactic agent against the virus. Following a rigorous assessment, the vaccine was built using T-cell (NCTL=8 and NHTL=6) and B-cell (NLBL=4) epitopes from each LASV-derived protein with suitable linkers and adjuvant. The physicochemistry, immunogenic potency and safeness of the designed vaccine (~68 kDa) were assessed. In addition, chosen CTL and HTL epitopes of our vaccine showed 97.37% worldwide population coverage. Besides, disulphide engineering also improved the stability of the chimeric vaccine. Molecular docking of our vaccine protein with toll-like receptor (TLR2) showed binding efficiency followed by dynamic simulation for stable interaction. Furthermore, higher levels of cell-mediated immunity and rapid antigen clearance were suggested by immune simulation and repeated-exposure simulation, respectively. Finally, the optimized codons were used in in silico cloning to ensure higher expression within E. coli K12 bacterium. With further assessment both in vitro and in vivo, we believe that our proposed peptide-vaccine would be potential immunogen against Lassa fever.

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Arenavirus Evasion of Host Anti-Viral Responses

Cited by 13 publications

References 50 publications

Highly Pathogenic New World and Old World Human Arenaviruses Induce Distinct Interferon Responses in Human Cells

Highly Pathogenic New World and Old World Human Arenaviruses Induce Distinct Interferon Responses in Human Cells

Genomic Profiling of Host Responses to Lassa Virus: Therapeutic Potential from Primate to Man

Immunoinformatics-Guided Designing of Peptide Vaccine against Lassa Virus with Dynamic and Immune Simulation Studies

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