Acute Phase CD8+T Lymphocytes against Alternate Reading Frame Epitopes Select for Rapid Viral Escape during SIV Infection

被引:11
作者
Walsh, Andrew D. [1 ]
Bimber, Benjamin N. [2 ]
Das, Arpita [3 ]
Piaskowski, Shari M. [4 ]
Rakasz, Eva G. [4 ]
Bean, Alexander T. [1 ]
Mudd, Philip A. [1 ,5 ]
Ericsen, Adam J. [1 ]
Wilson, Nancy A. [1 ]
Hughes, Austin L. [6 ]
O'Connor, David H. [1 ,4 ]
Maness, Nicholas J. [3 ,7 ]
机构
[1] Univ Wisconsin, Dept Pathol & Lab Med, Madison, WI USA
[2] Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Beaverton, OR USA
[3] Tulane Natl Primate Res Ctr, Div Microbiol, Covington, LA USA
[4] Univ Wisconsin, Wisconsin Natl Primate Res Ctr, Madison, WI USA
[5] Univ Wisconsin, Med Scientist Training Program, Madison, WI USA
[6] Univ S Carolina, Dept Biol Sci, Columbia, SC 29208 USA
[7] Tulane Univ, Sch Med, Dept Microbiol & Immunol, New Orleans, LA 70112 USA
来源
PLOS ONE | 2013年 / 8卷 / 05期
基金
美国国家卫生研究院;
关键词
SIMIAN IMMUNODEFICIENCY VIRUS; T-CELL RESPONSES; CRYPTIC EPITOPES; RHESUS MACAQUES; IN-VIVO; AIDS; REPLICATION; SIVMAC239; MUTATIONS; SUBSTITUTIONS;
D O I
10.1371/journal.pone.0061383
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
CD8+ T Lymphocytes (CTL) can control AIDS virus replication. However, natural selection favoring viral variants that escape CTL recognition is a common feature of both simian immunodeficiency virus (SIV) infection of macaques and HIV infection of humans. Emerging data indicate that CTL directed against alternate reading frame (ARF)-derived epitopes (a.k.a. cryptic epitopes) are important components of the total virus-specific response in SIV and HIV infection but the contributions of these responses during the critical first several weeks of infection have not been determined. We used a focused deep sequencing approach to examine acute phase viral evolution in response to CTL targeting two polypeptides encoded by ARFs of SIVmac239 in SIV-infected rhesus macaques. We report high magnitude CTL responses as early as three weeks post-infection against epitopes within both ARFs, which both overlap the 5' end of the env gene. Further, mutations accumulated in the epitopes by three to four weeks post infection consistent with viral escape. Interestingly, these mutations largely maintained the primary amino acid sequence of the overlapping Envelope protein. Our data show that high frequency CTL target cryptic epitopes and exert selective pressure on SIV during the acute phase, underscoring the importance of these unique immune responses.
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页数:10
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