Emergence intwochimpanzees ofhumanimmunodeficiency virus type1(HIV-1) IIIBvariants resistant to neutralization bythepreexisting antibody isdescribed. Viruses isolated fromtheHIV-1IUBgpl20-vaccinated and-challenged animal were more resistant toneutralization bythechimpanzee's own serum thanviruses isolated fromthenaive infected animal, indicating immunepressureastheselective mechanism. However, all reisolated viruses were 16-to256-fold more neutralization resistant thantheinoculum virus toantibodies binding tothethird variable domain(V3)oftheHIV-1external envelope. Earlychimpanzee serum samples thatneutralized theinoculum strain butnotthereisolated viruses were foundtobind an HIV-1MB common nonapeptide (IQRGPGRAF) derived fromthegpl20isolate-specific V3domainshowntoinduce isolate-specific neutralization inother animals. Amplification oftheV3coding sequencebypolymerase chainreaction and subsequent sequenceanalysis oftheneutralization-resistant variants obtained frominvivo-infected animals indicated thatearly resistance toneutralization byan HIV-1IUBmonoclonal antibody (0.5 1) was conferred bychanges outside thedirect binding site fortheselective neutralizing antibody. Thereisolated neutralizationresistant isolates consisted ofthelower-replication-competent virus subpopulation oftheHIV-1IHIBstock, as confirmed bybiological andsequenceanalyses. Invitro passageoftheHIV-1IIIBstock through chimpanzee andhumanperipheral bloodmononuclear cellcultures voidofHIV-specific antibody resulted inhomogenic amplification ofthemore-replication-competent subpopulation preexisting intheoriginal viral stock, suggestinga rolefortheimmunesysteminsuppressing themore-replication-competent viruses. Thehumanimmunodeficiency viruses types1and2(HIV
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