View All Abstracts for Session 23
110 Analysis of Coreceptor Usage among Sequential HIV-1 Subtype C Isolates from Acutely Infected Sex Workers in South Africa
M. Coetzer*1, T. Cilliers1, M. A. Papathanasopoulos1, G. Ramjee2, S. Abdool-Karim2, C. Williamson3, and L. Morris1
1Natl. Inst. for Virology, Johannesburg, South Africa; 2Med. Res. Council, Durban, South Africa; and 3Univ. of Cape Town, South Africa
Background: Entry of HIV-1 into host cells is dependent on the interaction of gp120 with CD4 and a coreceptor, either CCR5 or CXCR4. HIV-1 subtype C viruses predominantly use CCR5, unlike other viral subtypes that often switch to using CXCR4 during disease progression. This study investigated the genetic and phenotypic properties of sequential viral isolates collected over a 2-year period from a group of sex workers, 1 of whom showed significant disease progression.
Methods: A total of 24 viral isolates from 7 acutely infected sex workers were generated. Coreceptor usage was determined using U87.CD4 cell lines transfected with the appropriate coreceptor. The V3 region of gp120 was PCR amplified and analysed using a heteroduplex mobility assay (HMA). Full-length gp160 genes of 4 isolates from 1 patient were further investigated by cloning and sequencing.
Results: The initial isolate from 6 women used CCR5 and 1 used both CCR5 and CXCR4 (Du179). One patient (Du151) who was a rapid progressor developed isolates able to use both CCR5 and CXCR4. HMA profiles of Du151 show an increase in quasispecies variation with time. The gp160 from this patient showed major differences between NSI and SI isolates, including an increase in the overall positive charges of the V3 loop, altered N-linked glycosylation sites, and insertions of 10, 8, and 3 amino acids in the V1, V4, and V5 loops, respectively. However, the high degree of genetic variation in Du151 is likely due to coinfection with 2 different subtype C viruses rather than genetic evolution.
Conclusions: The data indicate that HIV-1 subtype C isolates can utilise CXCR4, and that in some individuals disease progression is associated with X4 tropic viruses.
Contact Author about this Abstract
