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High multiplicity infection by HIV-1 in men who have sex with men
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نویسنده
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li h. ,bar k.j. ,wang s. ,decker j.m. ,chen y. ,sun c. ,salazar-gonzalez j.f. ,salazar m.g. ,learn g.h. ,morgan c.j. ,schumacher j.e. ,hraber p. ,giorgi e.e. ,bhattacharya t. ,korber b.t. ,perelson a.s. ,eron j.j. ,cohen m.s. ,hicks c.b. ,haynes b.f. ,markowitz m. ,keele b.f. ,hahn b.h. ,shaw g.m.
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منبع
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plos pathogens - 2010 - دوره : 6 - شماره : 5 - صفحه:1 -17
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چکیده
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Elucidating virus-host interactions responsible for hiv-1 transmission is important for advancing hiv-1 prevention strategies. to this end,single genome amplification (sga) and sequencing of hiv-1 within the context of a model of random virus evolution has made possible for the first time an unambiguous identification of transmitted/founder viruses and a precise estimation of their numbers. here,we applied this approach to hiv-1 env analyses in a cohort of acutely infected men who have sex with men (msm) and found that a high proportion (10 of 28; 36%) had been productively infected by more than one virus. in subjects with multivariant transmission,the minimum number of transmitted viruses ranged from 2 to 10 with viral recombination leading to rapid and extensive genetic shuffling among virus lineages. a combined analysis of these results,together with recently published findings based on identical sga methods in largely heterosexual (hsx) cohorts,revealed a significantly higher frequency of multivariant transmission in msm than in hsx [19 of 50 subjects (38%) versus 34 of 175 subjects (19%); fisher's exact p = 0.008]. to further evaluate the sga strategy for identifying transmitted/founder viruses,we analyzed 239 overlapping 59 and 39 half genome or env-only sequences from plasma viral rna (vrna) and blood mononuclear cell dna in an msm subject who had a particularly well-documented virus exposure history 3-6 days before symptom onset and 14-17 days before peak plasma viremia (47,600,000 vrna molecules/ml). all 239 sequences coalesced to a single transmitted/founder virus genome in a time frame consistent with the clinical history,and a molecular clone of this genome encoded replication competent virus in accord with model predictions. higher multiplicity of hiv-1 infection in msm compared with hsx is consistent with the demonstrably higher epidemiological risk of virus acquisition in msm and could indicate a greater challenge for hiv-1 vaccines than previously recognized.
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آدرس
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department of medicine,university of alabama at birmingham,birmingham,al, United States, department of medicine,university of alabama at birmingham,birmingham,al, United States, department of medicine,university of alabama at birmingham,birmingham,al, United States, department of medicine,university of alabama at birmingham,birmingham,al, United States, department of medicine,university of alabama at birmingham,birmingham,al, United States, department of medicine,university of alabama at birmingham,birmingham,al, United States, department of medicine,university of alabama at birmingham,birmingham,al, United States, department of medicine,university of alabama at birmingham,birmingham,al, United States, department of medicine,university of alabama at birmingham,birmingham,al, United States, department of biostatistics,university of alabama at birmingham,birmingham,al, United States, department of medicine,university of alabama at birmingham,birmingham,al, United States, theoretical biology and biophysics (t6),los alamos national laboratory,los alamos,nm, United States, theoretical biology and biophysics (t6),los alamos national laboratory,los alamos,nm,united states,department of mathematics and statistics,university of massachusetts,amherst,ma, United States, nuclear and particle physics,astrophysics and cosmology (t-2),los alamos national laboratory,los alamos,nm,united states,santa fe institute,santa fe,nm, United States, theoretical biology and biophysics (t6),los alamos national laboratory,los alamos,nm,united states,santa fe institute,santa fe,nm, United States, theoretical biology and biophysics (t6),los alamos national laboratory,los alamos,nm, United States, department of medicine,university of north carolina,chapel hill,nc, United States, department of medicine,university of north carolina,chapel hill,nc, United States, department of medicine,duke university,durham,nc, United States, department of medicine,duke university,durham,nc, United States, aaron diamond aids research center,new york,ny,united states,rockefeller university,new york,ny, United States, saic-frederick,national cancer institute,frederick,md, United States, department of medicine,university of alabama at birmingham,birmingham,al,united states,department of microbiology,university of alabama at birmingham,birmingham,al, United States, department of medicine,university of alabama at birmingham,birmingham,al,united states,department of microbiology,university of alabama at birmingham,birmingham,al, United States
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Authors
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