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Expression profiles of host immune response-related genes against HEV genotype 3 and genotype 1 infections in rhesus macaques.

ABSTRACT: Hepatitis E virus (HEV) genotype (gt) 3 infection is food-borne causing sporadic infections in older individuals and gt1 infection is waterborne, often causing epidemics affecting primarily young adults. Although HEV infection causes self-limited disease, gt3 induces chronic infection in immunocompromised individuals. Hepatic host gene expression against gt3 infection remains unknown. Host gene expression profiles for HEV gt1 (n = 3) and gt3 (n = 7) infections were analysed in the livers of experimentally infected rhesus macaques. HEV RNA was detected from 2 to 24 days after inoculation (DAI) in stool and serum, elevated alanine aminotransferase (ALT) activity was detected from 7 to 31 DAI, and anti-HEV antibody became detectable between 12 and 42 DAI. All 10 animals cleared the infection between 34 and 68 DAI. We found that 24%, 48% and 41% of hepatic immune response genes against gt3 infection were upregulated during the early, peak and decline phases of HEV RNA replication. For gt1 infection, 25% of hepatic immune response-related genes were downregulated during early viremia, but 6%, 34% and 37% of genes were upregulated at the early, peak and during decline of HEV RNA replication, respectively. Our study demonstrated distinct differences in the expression profiles of host immune response-related genes of HEV gt3 and gt1 infections in experimentally infected rhesus macaques.

SUBMITTER: Choi YH

PROVIDER: S-EPMC8996335 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Expression profiles of host immune response-related genes against HEV genotype 3 and genotype 1 infections in rhesus macaques.

Choi Y H YH Zhang X X Tran C C Skinner B B

Journal of viral hepatitis 20180330 8

Hepatitis E virus (HEV) genotype (gt) 3 infection is food-borne causing sporadic infections in older individuals and gt1 infection is waterborne, often causing epidemics affecting primarily young adults. Although HEV infection causes self-limited disease, gt3 induces chronic infection in immunocompromised individuals. Hepatic host gene expression against gt3 infection remains unknown. Host gene expression profiles for HEV gt1 (n = 3) and gt3 (n = 7) infections were analysed in the livers of expe ...[more]

PMID: 29532615

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Project description:BACKGROUND:Considerable evidence has accumulated that multiple viruses, bacteria, and protozoa manipulate interleukin-10 (IL-10)-mediated signaling through the IL-10 receptor (IL-10R) in ways that could enable establishment of a persistent microbial infection. This suggests that inhibition of pathogen targeting of IL-10/IL-10R signaling could prevent microbial persistence. Human cytomegalovirus (HCMV) and rhesus cytomegalovirus (RhCMV) express a viral interleukin-10 (cmvIL-10 and rhcmvIL-10, respectively) with comparable immune modulating properties in vitro to that of their host's cellular IL-10 (cIL-10). A prior study noted that rhcmvIL-10 alters innate and adaptive immunity to RhCMV in vivo, consistent with a central role for rhcmvIL-10 during acute virus-host interactions. Since cmvIL-10 and rhcmvIL-10 are extremely divergent from the cIL-10 of their respective hosts, vaccine-mediated neutralization of their function could inhibit establishment of viral persistence without inhibition of cIL-10. METHODS AND FINDINGS:As a prelude to evaluating cmvIL-10-based vaccines in humans, the rhesus macaque model of HCMV was used to interrogate peripheral and mucosal immune responses to rhcmvIL-10 in RhCMV-infected animals. ELISA were used to detect rhcmvIL-10-binding antibodies in plasma and saliva, and an IL-12-based bioassay was used to quantify plasma antibodies that neutralized rhcmvIL-10 function. rhcmvIL-10 is highly immunogenic during RhCMV infection, stimulating high avidity rhcmvIL-10-binding antibodies in the plasma of all infected animals. Most infected animals also exhibited plasma antibodies that partially neutralized rhcmvIL-10 function but did not cross-neutralize the function of rhesus cIL-10. Notably, minimally detectable rhcmvIL-10-binding antibodies were detected in saliva. CONCLUSION:This study demonstrates that rhcmvIL-10, as a surrogate for cmvIL-10, is a viable vaccine candidate because (1) it is highly immunogenic during natural RhCMV infection, and (2) neutralizing antibodies to rhcmvIL-10 do not cross-react with rhesus cIL-10. Exceedingly low rhcmvIL-10 antibodies in saliva further suggest that the oral mucosa, which is critical in RhCMV natural history, is associated with suboptimal anti-rhcmvIL-10 antibody responses.

Dataset Information

Expression profiles of host immune response-related genes against HEV genotype 3 and genotype 1 infections in rhesus macaques.

Publications

Expression profiles of host immune response-related genes against HEV genotype 3 and genotype 1 infections in rhesus macaques.

Similar Datasets

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