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Recurrent signature patterns in hiv-1 b clade envelope glycoproteins associated with either early or chronic infections
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نویسنده
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gnanakaran s. ,bhattacharya t. ,daniels m. ,keele b.f. ,hraber p.t. ,lapedes a.s. ,shen t. ,gaschen b. ,krishnamoorthy m. ,li h. ,decker j.m. ,salazar-gonzalez j.f. ,wang s. ,jiang c. ,gao f. ,swanstrom r. ,anderson j.a. ,ping l.-h. ,cohen m.s. ,markowitz m. ,goepfert p.a. ,saag m.s. ,eron j.j. ,hicks c.b. ,blattner w.a. ,tomaras g.d. ,asmal m. ,letvin n.l. ,gilbert p.b. ,decamp a.c. ,magaret c.a. ,schief w.r. ,ban y.-e.a. ,zhang m. ,soderberg k.a. ,sodroski j.g. ,haynes b.f. ,shaw g.m. ,hahn b.h. ,korber b.
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منبع
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plos pathogens - 2011 - دوره : 7 - شماره : 9
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چکیده
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Here we have identified hiv-1 b clade envelope (env) amino acid signatures from early in infection that may be favored at transmission,as well as patterns of recurrent mutation in chronic infection that may reflect common pathways of immune evasion. to accomplish this,we compared thousands of sequences derived by single genome amplification from several hundred individuals that were sampled either early in infection or were chronically infected. samples were divided at the outset into hypothesis-forming and validation sets,and we used phylogenetically corrected statistical strategies to identify signatures,systematically scanning all of env. signatures included single amino acids,glycosylation motifs,and multi-site patterns based on functional or structural groupings of amino acids. we identified signatures near the ccr5 co-receptor-binding region,near the cd4 binding site,and in the signal peptide and cytoplasmic domain,which may influence env expression and processing. two signatures patterns associated with transmission were particularly interesting. the first was the most statistically robust signature,located in position 12 in the signal peptide. the second was the loss of an n-linked glycosylation site at positions 413-415; the presence of this site has been recently found to be associated with escape from potent and broad neutralizing antibodies,consistent with enabling a common pathway for immune escape during chronic infection. its recurrent loss in early infection suggests it may impact fitness at the time of transmission or during early viral expansion. the signature patterns we identified implicate env expression levels in selection at viral transmission or in early expansion,and suggest that immune evasion patterns that recur in many individuals during chronic infection when antibodies are present can be selected against when the infection is being established prior to the adaptive immune response. © 2011 this is an open-access article,free of all copyright,and may be freely reproduced,distributed,transmitted,modified,built upon,or otherwise used by anyone for any lawful purpose. the work is made available under the creative commons cc0 public domain dedication.
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آدرس
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theoretical biology,los alamos national laboratory,los alamos,nm, United States, theoretical biology,los alamos national laboratory,los alamos,nm,united states,santa fe institute,santa fe,nm, United States, theoretical biology,los alamos national laboratory,los alamos,nm, United States, saic-frederick,national cancer institute,frederick,md,united states,departments of medicine and microbiology,university of alabama at birmingham,birmingham,al, United States, theoretical biology,los alamos national laboratory,los alamos,nm, United States, theoretical biology,los alamos national laboratory,los alamos,nm, United States, theoretical biology,los alamos national laboratory,los alamos,nm,united states,center for molecular biophysics and department of biochemistry,cellular and molecular biology,university of tennessee,knoxville,tn, United States, theoretical biology,los alamos national laboratory,los alamos,nm, United States, theoretical biology,los alamos national laboratory,los alamos,nm, United States, departments of medicine and microbiology,university of alabama at birmingham,birmingham,al, United States, departments of medicine and microbiology,university of alabama at birmingham,birmingham,al, United States, departments of medicine and microbiology,university of alabama at birmingham,birmingham,al, United States, departments of medicine and microbiology,university of alabama at birmingham,birmingham,al, United States, national engineering laboratory of aids vaccine school of life science,jilin university,changchun,china,duke university medical center,the departments of medicine and surgery,duke human vaccine institute,duke university,durham,nc, United States, duke university medical center,the departments of medicine and surgery,duke human vaccine institute,duke university,durham,nc, United States, department of biochemistry and biophysics,division of infectious diseases center for aids research,university of north carolina at chapel hill,chapel hill,nc, United States, department of biochemistry and biophysics,division of infectious diseases center for aids research,university of north carolina at chapel hill,chapel hill,nc, United States, department of biochemistry and biophysics,division of infectious diseases center for aids research,university of north carolina at chapel hill,chapel hill,nc, United States, department of biochemistry and biophysics,division of infectious diseases center for aids research,university of north carolina at chapel hill,chapel hill,nc, United States, aaron diamond aids research center,an affiliate of the rockefeller university,new york,ny, United States, departments of medicine and microbiology,university of alabama at birmingham,birmingham,al, United States, departments of medicine and microbiology,university of alabama at birmingham,birmingham,al, United States, department of biochemistry and biophysics,division of infectious diseases center for aids research,university of north carolina at chapel hill,chapel hill,nc, United States, duke university medical center,the departments of medicine and surgery,duke human vaccine institute,duke university,durham,nc, United States, institute of human virology,university of maryland,school of medicine,baltimore,md, United States, duke university medical center,the departments of medicine and surgery,duke human vaccine institute,duke university,durham,nc, United States, beth israel deaconess medical center,boston,ma, United States, beth israel deaconess medical center,boston,ma,united states,division of viral pathogenesis,department of medicine,harvard medical school,boston,ma, United States, vaccine infectious disease division,fred hutchinson cancer research center,seattle,wa, United States, vaccine infectious disease division,fred hutchinson cancer research center,seattle,wa, United States, vaccine infectious disease division,fred hutchinson cancer research center,seattle,wa, United States, department of biochemistry,university of washington,seattle,wa, United States, department of biochemistry,university of washington,seattle,wa,united states,arzeda corporation,seattle,wa, United States, theoretical biology,los alamos national laboratory,los alamos,nm,united states,department of epidemiology and biostatistics,college of public health,university of georgia,athens,ga, United States, duke university medical center,the departments of medicine and surgery,duke human vaccine institute,duke university,durham,nc, United States, dana-farber cancer institute,department of cancer immunology and aids,boston,ma, United States, duke university medical center,the departments of medicine and surgery,duke human vaccine institute,duke university,durham,nc, United States, departments of medicine and microbiology,university of alabama at birmingham,birmingham,al, United States, departments of medicine and microbiology,university of alabama at birmingham,birmingham,al, United States, theoretical biology,los alamos national laboratory,los alamos,nm,united states,santa fe institute,santa fe,nm, United States
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Authors
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