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Whole genome deep sequencing of HIV-1 reveals the impact of early minor variants upon immune recognition during acute infection
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نویسنده
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henn m.r. ,boutwell c.l. ,charlebois p. ,lennon n.j. ,power k.a. ,macalalad a.r. ,berlin a.m. ,malboeuf c.m. ,ryan e.m. ,gnerre s. ,zody m.c. ,erlich r.l. ,green l.m. ,berical a. ,wang y. ,casali m. ,streeck h. ,bloom a.k. ,dudek t. ,tully d. ,newman r. ,axten k.l. ,gladden a.d. ,battis l. ,kemper m. ,zeng q. ,shea t.p. ,gujja s. ,zedlack c. ,gasser o. ,brander c. ,hess c. ,günthard h.f. ,brumme z.l. ,brumme c.j. ,bazner s. ,rychert j. ,tinsley j.p. ,mayer k.h. ,rosenberg e. ,pereyra f. ,levin j.z. ,young s.k. ,jessen h. ,altfeld m. ,birren b.w. ,walker b.d. ,allen t.m.
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منبع
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plos pathogens - 2012 - دوره : 8 - شماره : 3
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چکیده
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Deep sequencing technologies have the potential to transform the study of highly variable viral pathogens by providing a rapid and cost-effective approach to sensitively characterize rapidly evolving viral quasispecies. here,we report on a high-throughput whole hiv-1 genome deep sequencing platform that combines 454 pyrosequencing with novel assembly and variant detection algorithms. in one subject we combined these genetic data with detailed immunological analyses to comprehensively evaluate viral evolution and immune escape during the acute phase of hiv-1 infection. the majority of early,low frequency mutations represented viral adaptation to host cd8+ t cell responses,evidence of strong immune selection pressure occurring during the early decline from peak viremia. cd8+ t cell responses capable of recognizing these low frequency escape variants coincided with the selection and evolution of more effective secondary hla-anchor escape mutations. frequent,and in some cases rapid,reversion of transmitted mutations was also observed across the viral genome. when located within restricted cd8 epitopes these low frequency reverting mutations were sufficient to prime de novo responses to these epitopes,again illustrating the capacity of the immune response to recognize and respond to low frequency variants. more importantly,rapid viral escape from the most immunodominant cd8+ t cell responses coincided with plateauing of the initial viral load decline in this subject,suggestive of a potential link between maintenance of effective,dominant cd8 responses and the degree of early viremia reduction. we conclude that the early control of hiv-1 replication by immunodominant cd8+ t cell responses may be substantially influenced by rapid,low frequency viral adaptations not detected by conventional sequencing approaches,which warrants further investigation. these data support the critical need for vaccine-induced cd8+ t cell responses to target more highly constrained regions of the virus in order to ensure the maintenance of immunodominant cd8 responses and the sustained decline of early viremia. © 2012 henn et al.
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آدرس
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broad institute of mit and harvard,cambridge,ma, United States, ragon institute of mgh,mit and harvard,boston,ma, United States, broad institute of mit and harvard,cambridge,ma, United States, broad institute of mit and harvard,cambridge,ma, United States, ragon institute of mgh,mit and harvard,boston,ma, United States, broad institute of mit and harvard,cambridge,ma, United States, broad institute of mit and harvard,cambridge,ma, United States, broad institute of mit and harvard,cambridge,ma, United States, broad institute of mit and harvard,cambridge,ma, United States, broad institute of mit and harvard,cambridge,ma, United States, broad institute of mit and harvard,cambridge,ma, United States, broad institute of mit and harvard,cambridge,ma, United States, broad institute of mit and harvard,cambridge,ma, United States, ragon institute of mgh,mit and harvard,boston,ma, United States, ragon institute of mgh,mit and harvard,boston,ma, United States, broad institute of mit and harvard,cambridge,ma, United States, ragon institute of mgh,mit and harvard,boston,ma, United States, ragon institute of mgh,mit and harvard,boston,ma, United States, ragon institute of mgh,mit and harvard,boston,ma, United States, ragon institute of mgh,mit and harvard,boston,ma, United States, broad institute of mit and harvard,cambridge,ma, United States, ragon institute of mgh,mit and harvard,boston,ma, United States, ragon institute of mgh,mit and harvard,boston,ma, United States, ragon institute of mgh,mit and harvard,boston,ma, United States, ragon institute of mgh,mit and harvard,boston,ma, United States, broad institute of mit and harvard,cambridge,ma, United States, broad institute of mit and harvard,cambridge,ma, United States, broad institute of mit and harvard,cambridge,ma, United States, hiv clinic praxis,jessen,berlin, Germany, immunobiology lab,department of biomedicine,university hospital basel,basel, Switzerland, institució catalana de recerca i estudis avançats (icrea),barcelona,spain,irsicaixa aids research institute-hivacat,hospital university germans trias i pujol,badalona, Spain, immunobiology lab,department of biomedicine,university hospital basel,basel, Switzerland, division of infectious diseases and hospital epidemiology,university hospital zurich,university of zurich, Switzerland, ragon institute of mgh,mit and harvard,boston,ma, United States, ragon institute of mgh,mit and harvard,boston,ma, United States, massachusetts general hospital and harvard medical school,boston,ma, United States, massachusetts general hospital and harvard medical school,boston,ma, United States, the fenway institute,fenway health,boston,ma, United States, the fenway institute,fenway health,boston,ma, United States, massachusetts general hospital and harvard medical school,boston,ma, United States, ragon institute of mgh,mit and harvard,boston,ma, United States, broad institute of mit and harvard,cambridge,ma, United States, broad institute of mit and harvard,cambridge,ma, United States, hiv clinic praxis,jessen,berlin, Germany, ragon institute of mgh,mit and harvard,boston,ma, United States, broad institute of mit and harvard,cambridge,ma, United States, ragon institute of mgh,mit and harvard,boston,ma,united states,howard hughes medical institute,chevy chase,md, United States, ragon institute of mgh,mit and harvard,boston,ma, United States
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Authors
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