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In vivo virulence of MHC-adapted AIDS virus serially-passaged through MHC-mismatched hosts

CD8(+) T-cell responses exert strong suppressive pressure on HIV replication and select for viral escape mutations. Some of these major histocompatibility complex class I (MHC-I)-associated mutations result in reduction of in vitro viral replicative capacity. While these mutations can revert after v...

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Autores principales: Seki, Sayuri, Nomura, Takushi, Nishizawa, Masako, Yamamoto, Hiroyuki, Ishii, Hiroshi, Matsuoka, Saori, Shiino, Teiichiro, Sato, Hironori, Mizuta, Kazuta, Sakawaki, Hiromi, Miura, Tomoyuki, Naruse, Taeko K., Kimura, Akinori, Matano, Tetsuro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5624644/
https://www.ncbi.nlm.nih.gov/pubmed/28931083
http://dx.doi.org/10.1371/journal.ppat.1006638
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author Seki, Sayuri
Nomura, Takushi
Nishizawa, Masako
Yamamoto, Hiroyuki
Ishii, Hiroshi
Matsuoka, Saori
Shiino, Teiichiro
Sato, Hironori
Mizuta, Kazuta
Sakawaki, Hiromi
Miura, Tomoyuki
Naruse, Taeko K.
Kimura, Akinori
Matano, Tetsuro
author_facet Seki, Sayuri
Nomura, Takushi
Nishizawa, Masako
Yamamoto, Hiroyuki
Ishii, Hiroshi
Matsuoka, Saori
Shiino, Teiichiro
Sato, Hironori
Mizuta, Kazuta
Sakawaki, Hiromi
Miura, Tomoyuki
Naruse, Taeko K.
Kimura, Akinori
Matano, Tetsuro
author_sort Seki, Sayuri
collection PubMed
description CD8(+) T-cell responses exert strong suppressive pressure on HIV replication and select for viral escape mutations. Some of these major histocompatibility complex class I (MHC-I)-associated mutations result in reduction of in vitro viral replicative capacity. While these mutations can revert after viral transmission to MHC-I-disparate hosts, recent studies have suggested that these MHC-I-associated mutations accumulate in populations and make viruses less pathogenic in vitro. Here, we directly show an increase in the in vivo virulence of an MHC-I-adapted virus serially-passaged through MHC-I-mismatched hosts in a macaque AIDS model despite a reduction in in vitro viral fitness. The first passage simian immunodeficiency virus (1pSIV) obtained 1 year after SIVmac239 infection in a macaque possessing a protective MHC-I haplotype 90-120-Ia was transmitted into 90-120-Ia(-) macaques, whose plasma 1 year post-infection was transmitted into other 90-120-Ia(-) macaques to obtain the third passage SIV (3pSIV). Most of the 90-120-Ia-associated mutations selected in 1pSIV did not revert even in 3pSIV. 3pSIV showed lower in vitro viral fitness but induced persistent viremia in 90-120-Ia(-) macaques. Remarkably, 3pSIV infection in 90-120-Ia(+) macaques resulted in significantly higher viral loads and reduced survival compared to wild-type SIVmac239. These results indicate that MHC-I-adapted SIVs serially-transmitted through MHC-I-mismatched hosts can have higher virulence in MHC-I-matched hosts despite their lower in vitro viral fitness. This study suggests that multiply-passaged HIVs could result in loss of HIV-specific CD8(+) T cell responses in human populations and the in vivo pathogenic potential of these escaped viruses may be enhanced.
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spelling pubmed-56246442017-10-17 In vivo virulence of MHC-adapted AIDS virus serially-passaged through MHC-mismatched hosts Seki, Sayuri Nomura, Takushi Nishizawa, Masako Yamamoto, Hiroyuki Ishii, Hiroshi Matsuoka, Saori Shiino, Teiichiro Sato, Hironori Mizuta, Kazuta Sakawaki, Hiromi Miura, Tomoyuki Naruse, Taeko K. Kimura, Akinori Matano, Tetsuro PLoS Pathog Research Article CD8(+) T-cell responses exert strong suppressive pressure on HIV replication and select for viral escape mutations. Some of these major histocompatibility complex class I (MHC-I)-associated mutations result in reduction of in vitro viral replicative capacity. While these mutations can revert after viral transmission to MHC-I-disparate hosts, recent studies have suggested that these MHC-I-associated mutations accumulate in populations and make viruses less pathogenic in vitro. Here, we directly show an increase in the in vivo virulence of an MHC-I-adapted virus serially-passaged through MHC-I-mismatched hosts in a macaque AIDS model despite a reduction in in vitro viral fitness. The first passage simian immunodeficiency virus (1pSIV) obtained 1 year after SIVmac239 infection in a macaque possessing a protective MHC-I haplotype 90-120-Ia was transmitted into 90-120-Ia(-) macaques, whose plasma 1 year post-infection was transmitted into other 90-120-Ia(-) macaques to obtain the third passage SIV (3pSIV). Most of the 90-120-Ia-associated mutations selected in 1pSIV did not revert even in 3pSIV. 3pSIV showed lower in vitro viral fitness but induced persistent viremia in 90-120-Ia(-) macaques. Remarkably, 3pSIV infection in 90-120-Ia(+) macaques resulted in significantly higher viral loads and reduced survival compared to wild-type SIVmac239. These results indicate that MHC-I-adapted SIVs serially-transmitted through MHC-I-mismatched hosts can have higher virulence in MHC-I-matched hosts despite their lower in vitro viral fitness. This study suggests that multiply-passaged HIVs could result in loss of HIV-specific CD8(+) T cell responses in human populations and the in vivo pathogenic potential of these escaped viruses may be enhanced. Public Library of Science 2017-09-20 /pmc/articles/PMC5624644/ /pubmed/28931083 http://dx.doi.org/10.1371/journal.ppat.1006638 Text en © 2017 Seki et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Seki, Sayuri
Nomura, Takushi
Nishizawa, Masako
Yamamoto, Hiroyuki
Ishii, Hiroshi
Matsuoka, Saori
Shiino, Teiichiro
Sato, Hironori
Mizuta, Kazuta
Sakawaki, Hiromi
Miura, Tomoyuki
Naruse, Taeko K.
Kimura, Akinori
Matano, Tetsuro
In vivo virulence of MHC-adapted AIDS virus serially-passaged through MHC-mismatched hosts
title In vivo virulence of MHC-adapted AIDS virus serially-passaged through MHC-mismatched hosts
title_full In vivo virulence of MHC-adapted AIDS virus serially-passaged through MHC-mismatched hosts
title_fullStr In vivo virulence of MHC-adapted AIDS virus serially-passaged through MHC-mismatched hosts
title_full_unstemmed In vivo virulence of MHC-adapted AIDS virus serially-passaged through MHC-mismatched hosts
title_short In vivo virulence of MHC-adapted AIDS virus serially-passaged through MHC-mismatched hosts
title_sort in vivo virulence of mhc-adapted aids virus serially-passaged through mhc-mismatched hosts
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5624644/
https://www.ncbi.nlm.nih.gov/pubmed/28931083
http://dx.doi.org/10.1371/journal.ppat.1006638
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