SYNCYTIUM-INDUCING (SI) PHENOTYPE SUPPRESSION AT SEROCONVERSION AFTERINTRAMUSCULAR INOCULATION OF A NON-SYNCYTIUM-INDUCING SI PHENOTYPICALLY MIXED HUMAN-IMMUNODEFICIENCY-VIRUS POPULATION/

Two distinct biological phenotypes of human immunodeficiency virus (HI V) have been described: the non-syncytium-inducing (NSI) phenotype, be st characterized by the inability to infect MT-2 cells, and the syncyt ium-inducing (SI) phenotype, with the ability to infect MT-2 cells. Th e earliest virus population observed following HIV transmission is gen erally of the NSI phenotype, even after exposure to inocula of mixed N SI/SI phenotype. In this study, the issue of intrapatient selection of virus phenotype following transmission was addressed by studying two cases of accidental transmission. A comparison of the sequences of the V1-V2 and the V3 coding regions of the envelope gene and the p17 regi on of the gag gene showed that the donor-recipient pairs were tightly clustered in ah gene segments, but away from local and published trans mission controls. The intrasample variation of the p17 sequence was gr eater in the recipients and smaller in the donors than that of the V3 region sequence, indicating selection of V3 at transmission. In these transmission cases, the effects of an intravenous inoculation of a sma ll quantity of blood containing predominantly SI V3 sequences (6 of 8 clonal sequences) were compared with those of an intramuscular inocula tion of a large quantity of blood containing predominantly NSI viruses (14 of 16 clonal sequences). Both SI and NSI V3 regions were demonstr ated to be phenotypic expressions of genetically related viral strains . The inoculation of the predominantly SI virus population resulted in the persistence of an SI virus population in the recipient and a rapi d CD4(+) T-cell decline. The inoculation of the predominantly NSI popu lation resulted in a selective amplification of SI viruses before sero conversion, followed by a suppression of SI viruses at seroconversion and a rapid decline of CD4(+) T-cell numbers. These data suggest that the suppression of SI viruses can be accomplished following the develo pment of HIV-specific immunity and that the ability to suppress SI vir uses does not prevent the development of immunodeficiency.