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Role of APOBEC3F Gene Variation in HIV-1 Disease Progression and Pneumocystis Pneumonia
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نویسنده
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an p. ,penugonda s. ,thorball c.w. ,bartha i. ,goedert j.j. ,donfield s. ,buchbinder s. ,binns-roemer e. ,kirk g.d. ,zhang w. ,fellay j. ,yu x.-f. ,winkler c.a.
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منبع
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plos genetics - 2016 - دوره : 12 - شماره : 3
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چکیده
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Human apobec3 cytidine deaminases are intrinsic resistance factors to hiv-1. however,hiv-1 encodes a viral infectivity factor (vif) that degrades apobec3 proteins. in vitro apobec3f (a3f) anti-hiv-1 activity is weaker than a3g but is partially resistant to vif degradation unlike a3g. it is unknown whether a3f protein affects hiv-1 disease in vivo. to assess the effect of a3f gene on host susceptibility to hiv- acquisition and disease progression,we performed a genetic association study in six well-characterized hiv-1 natural cohorts. a common six-single nucleotide polymorphism (snp) haplotype of a3f tagged by a codon-changing variant (p. i231v,with allele (v) frequency of 48% in european americans) was associated with significantly lower set-point viral load and slower rate of progression to aids (relative hazards (rh) = 0.71,95% ci: 0.56,0.91) and delayed development of pneumocystis pneumonia (pcp) (rh = 0.53,95% ci: 0.37–0.76). a validation study in the international collaboration for the genomics of hiv (icgh) showed a consistent association with lower set-point viral load. an in vitro assay revealed that the a3f i231v variant may influence vif mediated a3f degradation. our results provide genetic epidemiological evidence that a3f modulates hiv-1/aids disease progression. © 2016,public library of science. all rights reserved.
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آدرس
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basic research laboratory,center for cancer research,national cancer institute,leidos biomedical research,inc.,frederick national laboratory for cancer research,frederick,md, United States, department of medicine,northwestern university feinberg school of medicine,chicago,il, United States, school of life sciences,école polytechnique fédérale de lausanne,lausanne,switzerland,swiss institute of bioinformatics,lausanne, Switzerland, school of life sciences,école polytechnique fédérale de lausanne,lausanne,switzerland,swiss institute of bioinformatics,lausanne, Switzerland, infections and immunoepidemiology branch,division of cancer epidemiology and genetics,national cancer institute,bethesda,md, United States, rho,inc.,chapel hill,nc, United States, san francisco department of public health,san francisco,ca, United States, basic research laboratory,center for cancer research,national cancer institute,leidos biomedical research,inc.,frederick national laboratory for cancer research,frederick,md, United States, department of epidemiology,johns hopkins school of public health,baltimore,md, United States, institute of virology and aids research,first hospital of jilin university,changchun, China, school of life sciences,école polytechnique fédérale de lausanne,lausanne,switzerland,swiss institute of bioinformatics,lausanne, Switzerland, institute of virology and aids research,first hospital of jilin university,changchun,china,department of molecular microbiology and immunology,johns hopkins school of public health,baltimore,md, United States, basic research laboratory,center for cancer research,national cancer institute,leidos biomedical research,inc.,frederick national laboratory for cancer research,frederick,md, United States
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Authors
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