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Characterizing monkeypox virus specific CD8+ T cell epitopes in rhesus macaques.

ABSTRACT: To characterize T cell epitopes in monkeypox virus (MPXV) infected rhesus macaques, we utilized IFN? Elispot assay to screen 400 predicted peptides from 20MPXV proteins. Two peptides from the F8L protein, an analog of E9L protein in vaccinia, were found to elicit CD8+ T cell responses. Prediction and in vitro MHC binding analyses suggest that one is restricted by Mamu-A1(?)001 and another by Mamu-A1(?)002. The Mamu-A1(?)002 epitope is completely identical in all reported sequences for variola, vaccinia, cowpox and MPXV. The Mamu-A1(?)001 epitope is conserved in MPXV and vaccinia, and has one residue substitution (V6>I) in some cowpox sequences and all variola sequences. Given CD8+ T-cell epitopes from E9L were also identified in humans and mice, our data suggested that F8L/E9L may be a dominant pox viral protein for CD8+ T cell responses, and may be considered as a target when designing vaccines that target pox-specific T cell responses.

SUBMITTER: Song H

PROVIDER: S-EPMC4771384 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature

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Characterizing monkeypox virus specific CD8+ T cell epitopes in rhesus macaques.

Song Haifeng H Sidney John J Wiseman Roger W RW Josleyn Nicole N Cohen Melanie M Blaney Joseph E JE Jahrling Peter B PB Sette Alessandro A

Virology 20130928 1-2

To characterize T cell epitopes in monkeypox virus (MPXV) infected rhesus macaques, we utilized IFNγ Elispot assay to screen 400 predicted peptides from 20MPXV proteins. Two peptides from the F8L protein, an analog of E9L protein in vaccinia, were found to elicit CD8+ T cell responses. Prediction and in vitro MHC binding analyses suggest that one is restricted by Mamu-A1(⁎)001 and another by Mamu-A1(⁎)002. The Mamu-A1(⁎)002 epitope is completely identical in all reported sequences for variola, v ...[more]

PMID: 24210113

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Project description:Background & aimsHEV is a significant cause of acute hepatitis globally. Some genotypes establish persistent infection when immunity is impaired. Adaptive immune mechanisms that mediate resolution of infection have not been identified. Herein, the requirement for CD8+ T cells to control HEV infection was assessed in rhesus macaques, a model of acute and persistent HEV infection in humans.MethodsRhesus macaques were untreated or treated with depleting anti-CD8α monoclonal antibodies before challenge with an HEV genotype (gt)3 isolate derived from a chronically infected human patient. HEV replication, alanine aminotransferase, anti-capsid antibody and HEV-specific CD4+ and CD8+ T cell responses were assessed after infection.ResultsHEV control in untreated macaques coincided with the onset of a neutralizing IgG response against the ORF2 capsid and liver infiltration of functional HEV-specific CD4+ and CD8+ T cells. Virus control was delayed by 1 week in CD8+ T cell-depleted macaques. Infection resolved with onset of a neutralizing IgG antibody response and a much more robust expansion of CD4+ T cells with antiviral effector function.ConclusionsLiver infiltration of functional CD8+ T cells coincident with HEV clearance in untreated rhesus macaques, and a 1-week delay in HEV clearance in CD8+ T cell-depleted rhesus macaques, support a role for this subset in timely control of virus replication. Resolution of infection in the absence of CD8+ T cells nonetheless indicates that neutralizing antibodies and/or CD4+ T cells may act autonomously to inhibit HEV replication. HEV susceptibility to multiple adaptive effector mechanisms may explain why persistence occurs only with generalized immune suppression. The findings also suggest that neutralizing antibodies and/or CD4+ T cells should be considered as a component of immunotherapy for chronic infection.Lay summaryThe hepatitis E virus (HEV) is a major cause of liver disease globally. Some genetic types (genotypes) of HEV persist in the body if immunity is impaired. Our objective was to identify immune responses that promote clearance of HEV. Findings indicate that HEV may be susceptible to multiple arms of the immune response that can act independently to terminate infection. They also provide a pathway to assess immune therapies for chronic HEV infection.

Dataset Information

Characterizing monkeypox virus specific CD8+ T cell epitopes in rhesus macaques.

Publications

Characterizing monkeypox virus specific CD8+ T cell epitopes in rhesus macaques.

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