|
|
|
|
Genotypic and Functional Impact of HIV-1 Adaptation to Its Host Population during the North American Epidemic
|
|
|
|
|
|
|
|
نویسنده
|
cotton l.a. ,kuang x.t. ,le a.q. ,carlson j.m. ,chan b. ,chopera d.r. ,brumme c.j. ,markle t.j. ,martin e. ,shahid a. ,anmole g. ,mwimanzi p. ,nassab p. ,penney k.a. ,rahman m.a. ,milloy m.-j. ,schechter m.t. ,markowitz m. ,carrington m. ,walker b.d. ,wagner t. ,buchbinder s. ,fuchs j. ,koblin b. ,mayer k.h. ,harrigan p.r. ,brockman m.a. ,poon a.f.y. ,brumme z.l.
|
|
منبع
|
plos genetics - 2014 - دوره : 10 - شماره : 4
|
|
چکیده
|
Hla-restricted immune escape mutations that persist following hiv transmission could gradually spread through the viral population,thereby compromising host antiviral immunity as the epidemic progresses. to assess the extent and phenotypic impact of this phenomenon in an immunogenetically diverse population,we genotypically and functionally compared linked hla and hiv (gag/nef) sequences from 358 historic (1979-1989) and 382 modern (2000-2011) specimens from four key cities in the north american epidemic (new york,boston,san francisco,vancouver). inferred hiv phylogenies were star-like,with approximately two-fold greater mean pairwise distances in modern versus historic sequences. the reconstructed epidemic ancestral (founder) hiv sequence was essentially identical to the north american subtype b consensus. consistent with gradual diversification of a consensus-like founder virus,the median background frequencies of individual hla-associated polymorphisms in hiv (in individuals lacking the restricting hla[s]) were ∼2-fold higher in modern versus historic hiv sequences,though these remained notably low overall (e.g. in gag,medians were 3.7% in the 2000s versus 2.0% in the 1980s). hiv polymorphisms exhibiting the greatest relative spread were those restricted by protective hlas. despite these increases,when hiv sequences were analyzed as a whole,their total average burden of polymorphisms that were pre-adapted to the average host hla profile was only ∼2% greater in modern versus historic eras. furthermore,hla-associated polymorphisms identified in historic hiv sequences were consistent with those detectable today,with none identified that could explain the few hiv codons where the inferred epidemic ancestor differed from the modern consensus. results are therefore consistent with slow hiv adaptation to hla,but at a rate unlikely to yield imminent negative implications for cellular immunity,at least in north america. intriguingly,temporal changes in protein activity of patient-derived nef (though not gag) sequences were observed,suggesting functional implications of population-level hiv evolution on certain viral proteins. © 2014 cotton et al.
|
|
|
|
|
آدرس
|
simon fraser university,burnaby,bc, Canada, department of molecular biology and biochemistry,simon fraser university,burnaby,bc, Canada, simon fraser university,burnaby,bc, Canada, microsoft research,los angeles,ca, United States, simon fraser university,burnaby,bc, Canada, simon fraser university,burnaby,bc,canada,kwazulu-natal research institute for tuberculosis and hiv,nelson r. mandela school of medicine,university of kwazulu-natal,durban,kwazulu-natal, South Africa, british columbia centre for excellence in hiv/aids,vancouver,bc, Canada, department of molecular biology and biochemistry,simon fraser university,burnaby,bc, Canada, department of molecular biology and biochemistry,simon fraser university,burnaby,bc,canada,british columbia centre for excellence in hiv/aids,vancouver,bc, Canada, simon fraser university,burnaby,bc, Canada, department of molecular biology and biochemistry,simon fraser university,burnaby,bc, Canada, simon fraser university,burnaby,bc, Canada, simon fraser university,burnaby,bc, Canada, simon fraser university,burnaby,bc, Canada, simon fraser university,burnaby,bc, Canada, british columbia centre for excellence in hiv/aids,vancouver,bc,canada,university of british columbia,vancouver,bc, Canada, university of british columbia,vancouver,bc, Canada, aaron diamond aids research center,the rockefeller university,new york,ny, United States, cancer and inflammation program,laboratory of experimental immunology,leidos biomedical research inc.,frederick national laboratory for cancer research,frederick,md,united states,ragon institute of mgh,mit and harvard university,cambridge,ma, United States, ragon institute of mgh,mit and harvard university,cambridge,ma, United States, san francisco department of public health,san francisco,ca, United States, san francisco department of public health,san francisco,ca, United States, san francisco department of public health,san francisco,ca, United States, new york blood center,new york,ny, United States, fenway community health,boston,ma,united states,harvard medical school,boston,ma, United States, british columbia centre for excellence in hiv/aids,vancouver,bc,canada,university of british columbia,vancouver,bc, Canada, simon fraser university,burnaby,bc,canada,department of molecular biology and biochemistry,simon fraser university,burnaby,bc,canada,british columbia centre for excellence in hiv/aids,vancouver,bc, Canada, simon fraser university,burnaby,bc,canada,british columbia centre for excellence in hiv/aids,vancouver,bc,canada,university of british columbia,vancouver,bc, Canada, simon fraser university,burnaby,bc,canada,british columbia centre for excellence in hiv/aids,vancouver,bc, Canada
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Authors
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|