Genotypic Characterization and Comparison of Full-Length Envelope Glycoproteins from South African HIV Type 1 Subtype C Primary Isolates That Utilize CCR5 and/or CXCR4

Abstract

CCR5 has preferentially been used by all circulating HIV-1 subtype C viruses for cell entry. Recently, we reported the highest proportion of CXCR4-utilizing primary isolates among a cohort of 20 South African AIDS patients. This study describes and compares the Env genotypic characteristics from these 20 HIV-1 subtype C (and unique CD recombinant) primary isolates. Fourteen primary isolates utilized CCR5, four (including the CD recombinant) used CXCR4, and two were dual tropic. Extensive analysis and comparison of important structural motifs such as the N-linked glycosylation sites, signal sequences, CD4-binding sites, variable loops, cleavage sites, known neutralizing antibody and small molecule inhibitor binding sites confirmed that other than the expected differences in the V3 loop, no sequence motifs distinguished between R5 and X4 tropism. Further correlation of the env genotype to functionally relevant motifs is necessary to elucidate the relationship between biologically and immunologically relevant sites and aid vaccine and novel drug design.

Transmitted HIV Type 1 Drug Resistance Among Individuals with Recent HIV Infection in East and Southern Africa

“…Recombinants were further evaluated with the Recombinant Identification program (RIP 3.0) and jumping profile Hidden Markov Model 25 (jpHMM-HIV; http://www.hiv.lanl.gov). In addition, matched env was PCR amplified, sequenced, and extensively analyzed 26 for further clarification of selected samples. When sequence data were available, epidemiological linkage for suspected 6 PRICE ET AL.…”

Prediction of HIV Type 1 Subtype C Tropism by Genotypic Algorithms Built From Subtype B Viruses

“…[16][17][18][19][20] However, recent studies have found CXCR4-using viruses in about 30% of subtype C-infected patients with advanced disease. [21][22][23][24][25] Whether this apparent increased frequency of CXCR4-using subtype C viruses is due to better detection, the selection of CXCR4-using variants due to antiretroviral therapy, or an evolving epidemic, remains to be determined. Little is known about the genotypic determinants of CXCR4 coreceptor usage by subtype C viruses, and this information is crucial before genotypic analyses can be used to predict the tropism of this subtype.…”

Performance of Genotypic Tools for Prediction of Tropism in HIV-1 Subtype C V3 Loop Sequences

“…We compiled a dataset of 645 HIV-1 subtype C V3 loop sequences of known coreceptor phenotypes based on coreceptor-transfected cell lines for CCR5 or CXCR4 coreceptor usage or MT-2 cells for non-syncytium-inducing (NSI) and syncytium-inducing (SI) properties, from the Los Alamos database (http://www.hiv.lanl.gov/) and from previously published literature [6,7,8,9]. Sequences containing #, $ or * were eliminated from the dataset.…”