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

Abstract

The genotypic determinants of coreceptor usage for HIV-1 subtype C were mainly in V3 and were globally similar to those previously reported for subtype B viruses. The main genotypic algorithms built from subtype B viruses perform well when applied to subtype C viruses.

Genotypic Prediction of HIV-1 CRF01-AE Tropism

“…The loss of the N-linked glycosylation site at the beginning of V3 was an independent determinant of CXCR4 use by the CRF01-AE virus clones. This mutation is known to be associated with CXCR4 use by subtype B and subtype C viruses (10,(24)(25)(26). We therefore designed a genotypic algorithm specific for HIV-1 subtype CRF01-AE that combined the criteria of 11/25, net charge, and NXT/S mutation.…”

“…Genetic variations in the envelope gene influence the genotypic prediction of HIV-1 tropism that relies on data on the correlation between genotype and phenotype obtained in countries where subtype B viruses predominate. But the performance of genotypic algorithms can differ from one HIV-1 subtype to another and must be validated for each particular subtype (6)(7)(8)(9)(10)(11).…”

Generation of Lineage-Related, Mucosally Transmissible Subtype C R5 Simian-Human Immunodeficiency Viruses Capable of AIDS Development, Induction of Neurological Disease, and Coreceptor Switching in Rhesus Macaques

“…However, most challenge stocks currently available express envelopes from culture-derived HIV-1 clade B strains, which represent ϳ10% of all infections globally and are substantially different in sequence and envelope antigenic structure from the most predominant subtype C strains. Indeed, while coreceptor switching has been documented in 40 to 50% of individuals infected with subtype B and D viruses and is associated with faster disease progression, it is found less frequently in patients infected with subtypes A and C (19,20), leading to the suggestion that intrinsic differences in V3 conformation and/or evolutionary pathways to efficient CXCR4 (X4) usage between subtypes may be playing a role (21)(22)(23). Several SHIVs containing subtype C envelopes (SHIVCs) have been described (24)(25)(26)(27)(28), but not all the SHIVCs utilize the CCR5 molecule exclusively as an entry coreceptor.…”

Differential Expression of Rac-1, Cxcr4 and CCR5 on CD4 T-Cells at Different Stages of HIV-1 Disease Relate To Its Progression in Therapy Naive Individuals

“…On the other hand, in advanced stage of the disease with CD4 count <250 cells/μl, the number of CCR5 positive Treg were significantly lower when compared to HIV-1 individuals in early stage of disease (p=0.0022). With previous reports in non-subtype C infections, the depletion of CCR5 expressing memory cells in acute infection may drive viral evolution towards CXCR4 [28,29], and recent reports showing about 30% of CXCR4-utilising viruses in untreated and treated HIV-1 subtype C infected adults from South Africa, Malawi, and Zimbabwe, suggesting a shift in viral properties [30][31][32]. This change in CCR5 expression might be responsible for increase in the frequency of Treg cells in the advanced stages of the disease.…”