HIV-1 subtype C in vitro growth and coreceptor utilization

Abstract

Human immunodeficiency virus type 1 subtype C (HIV-1C) accounts for about 50% of all HIV infections in the pandemic and is the predominant subtype in the heavily burdened region of southern Africa. HIV-1C possesses unique genetic and phenotypic features that might be associated with biological differences compared to other subtypes. Here, we generated virus isolates from individuals at different stages of HIV-1C infection and investigated the chemokine receptor repertoire that the derived HIV-1C isolates may utilize for entry. Our results show that the R5 phenotype predominates among viruses in Botswana, with a lesser contribution of viruses showing the dualtropic X4R5 phenotype. No viruses of pure X4 phenotype were found, which suggests no discernable evolution of HIV-1C to a monotropic X4 phenotype as the epidemic ages in Botswana. Usage of other coreceptors was rare and apparently insignificant. These results enhance our understanding of HIV-1C biology, with implications for designing and testing therapeutic and prophylactic agents.

Heterosexual Transmission of Human Immunodeficiency Virus Type 1 Subtype C: Macrophage Tropism, Alternative Coreceptor Use, and the Molecular Anatomy of CCR5 Utilization

“…Prior studies have also found little or no CCR2b and CCR3 use by subtype C HIV-1. However, our findings differ somewhat from the previously reported infrequent use of GPR15 and CXCR6 in subtype C (1,6,9,38,39). Additional isolates will be needed to determine if the use of these molecules is widespread among certain cohorts or if it reflects particular biological properties linked to other aspects of pathogenesis.…”

Evaluation of Eight Different Bioinformatics Tools To Predict Viral Tropism in Different Human Immunodeficiency Virus Type 1 Subtypes

“…Up to 19% of these individuals carried X4/X4R5 dual-tropic viruses, with no significant differences with a control group of patients infected with clade B viruses. In other studies that included a larger number of samples from clades C and D, it was noted that clade C might less frequently harbor X4 viruses, even in late disease stages (8,16,20,24,31), while conversely, clade D could be X4 tropic more frequently (10,14). The small number of samples with these variants in our study precluded the examination of this aspect more appropriately.…”

Analysis of Dominant HIV Quasispecies Suggests Independent Viral Evolution Within Spinal Granulomas Coinfected with Mycobacterium tuberculosis and HIV-1 Subtype C

“…33 Our findings established CCR5-utilizing variants in both plasma and tissue in all but two sequences; this is consistent with previous studies of HIV-1 subtype C infections showing minimal corrector switch from CCR5 to CXCR4 even in the context of late stage AIDS and coinfections such as pulmonary TB. 28 Phenotypic studies may be warranted since genotype does not always accurately predict coreceptor utilization and subtle differences in usage of CD4 and coreceptors have been noted with CSF-derived and other viral isolates. 34,35 Given the prominent role of macrophages in the anti-TB immune response we explored their composition in the granulomas and found evidence of HIV-infected macrophages.…”

“…Since key viral determinants of cell tropism and coreceptor usage are located within the env V3 loop, 28 we investigated whether there were V3 loop amino acid differences between plasma-derived and tissue-derived sequences ( Table 2). The biochemical properties (charge, size, hydrophobicity) at the amino acid positions determining the folding patterns of the V3 loop were similar and indicative of predominantly CCR5-utilizing variants in plasma and tissue.…”