Syncytium-inducing (SI) phenotype suppression at seroconversion after intramuscular inoculation of a non-syncytium-inducing/SI phenotypically mixed human immunodeficiency virus population

Abstract

Two distinct biological phenotypes of human immunodeficiency virus (HIV) have been described: the non-syncytium-inducing (NSI) phenotype, best characterized by the inability to infect MT-2 cells, and the syncytium-inducing (SI) phenotype, with the ability to infect MT-2 cells. The earliest virus population observed following HIV transmission is generally of the NSI phenotype, even after exposure to inocula of mixed NSI/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 region of the gag gene showed that the donor-recipient pairs were tightly clustered in all gene segments, but away from local and published transmission controls. The intrasample variation of the p17 sequence was greater 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 small quantity of blood containing predominantly SI V3 sequences (6 of 8 clonal sequences) were compared with those of an intramuscular inoculation of a large quantity of blood containing predominantly NSI viruses (14 of 16 clonal sequences). Both SI and NSI V3 regions were demonstrated 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 rapid CD4+ T-cell decline. The inoculation of the predominantly NSI population resulted in a selective amplification of SI viruses before seroconversion, 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 development of HIV-specific immunity and that the ability to suppress SI viruses does not prevent the development of immunodeficiency.

The epidemiology and clinical correlates of HIV‐1 co‐receptor tropism in non‐subtype B infections from India, Uganda and South Africa

“…For example, some similarities can be observed between the findings of the present study and a previous study that assessed co-receptor tropism of HIV-1 strains in China: mainly that R5 tropism was seen exclusively in subtype C infections, and remained stable over time [24]. These data highlight the persistence of CCR5 tropism even in long-term infections, possibly related to differences within the env variable loops [37], and contrasts with other subtypes, especially subtype B, where X4 HIV-1 is more frequent during later stages of infection [6,[8][9][10]16,18,21,[37][38][39][40].…”

“…Studies of HIV-1 co-receptor tropism, which have been conducted primarily in populations where subtype B infections predominate, have demonstrated a relationship between HIV-1 co-receptor use and disease stage. In general, early stages of infection and disease are characterized by greater prevalence of only C-C chemokine type 5 (CCR5)-tropic (R5) HIV-1, which has been associated with slower progression to AIDS [8][9][10][11][12]. The emergence of C-X-C chemokine receptor type 4 (CXCR4)-using virus (X4) has been associated with greater treatment experience and higher risk of death, and coincides with more rapid CD4 + T-cell depletion and disease progression [6,8,9,12,13].…”

“…In general, early stages of infection and disease are characterized by greater prevalence of only C-C chemokine type 5 (CCR5)-tropic (R5) HIV-1, which has been associated with slower progression to AIDS [8][9][10][11][12]. The emergence of C-X-C chemokine receptor type 4 (CXCR4)-using virus (X4) has been associated with greater treatment experience and higher risk of death, and coincides with more rapid CD4 + T-cell depletion and disease progression [6,8,9,12,13]. Some variants of HIV-1 can use either co-receptor (dual/mixed-tropic [DM] HIV-1); these can be found in all stages of infection, but are more common in infections of longer duration, with lower CD4 + cell counts and higher viral loads [12][13][14].…”

Detection of HIV-RNA-positive monocytes in peripheral blood of HIV-positive patients by simultaneous flow cytometric analysis of intracellular HIV RNA and cellular immunophenotype

“…The extent to which HIV infects and replicates in these various cell populations has important implications when considering the known effects of HIV gene expression on the function of various cell types (5,37) and the therapeutic potential of blocking cell type specific coreceptors required for HIV infection (1,10). In addition, different HIV-infected cell populations are important during disease transmission and dissemination from portals of entry (8,41) versus disease progression (7). Also, given the finite number of target cells for HIV infection, knowledge of the specific infected cell types in addition to plasma free virus levels will be important in understanding disease progression (23).…”

Evidence for a role of T‐helper type 2 cytokines in the acquisition of human immunodeficiency virus syncytium‐inducing phenotype

“…Several studies have demonstrated that mixtures of viruses with different phenotypes are always circulating in an infected patient [6]. Viruses with the NSI phenotype are predominant in individuals with early or stable HIV infection, but some SI viruses are almost invariably present [33,34]. As HIV infection progresses, the initially dominant NSI viruses are usually replaced by SI viruses [6].…”