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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
immunology and microbiology
Genetic characteristics of the V3 region associated with CXCR4 usage in HIV-1 subtype C isolates
Virology, Volume 356, No. 1-2, Year 2006
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Description
CXCR4 coreceptor usage appears to occur less frequently among HIV-1 subtype C viruses. The aim of this study was to investigate the genetic determinants within the V3 region of subtype C isolates able to use CXCR4. Thirty-two subtype C isolates with known phenotypes (16 R5, 8 R5X4 and 8 X4 isolates) were assessed. A subtype C-specific V3 heteroduplex tracking assay (HTA) was used to determine sample complexity, and nucleotide sequencing analysis was used to compare characteristics associated with CCR5 and CXCR4-using isolates. There were sufficient genetic differences to discriminate between R5 viruses and those able to use CXCR4. In general, R5 isolates had an HTA mobility ratio >0 .9 whereas CXCR4-using isolates were usually < 0.9. Multiple bands were more frequently seen among the dualtropic isolates. Sequence analysis of the V3 region showed that CXCR4-using viruses were often associated with an increased positive amino acid charge, insertions and loss of a glycosylation site, similar to HIV-1 subtype B. In contrast, where subtype B consensus V3 has a GPGR crown motif irrespective of coreceptor usage, all 16 subtype C R5 viruses had a conserved GPGQ sequence at the tip of the loop, while 12 of the 16 (75%) CXCR4-using viruses had substitutions in this motif, most commonly arginine (R). These findings were confirmed using a larger published data set. We therefore suggest that changes within the crown motif of subtype C viruses might be an additional pathway to utilise CXCR4 and thus GPGQ may limit the potential for the development of X4 viruses. © 2006 Elsevier Inc. All rights reserved.
Authors & Co-Authors
Coetzer, Mia E.
South Africa, Johannesburg
National Institute for Communicable Diseases
Cilliers, Tonie
South Africa, Johannesburg
National Institute for Communicable Diseases
Ping, Lihua
United States, Chapel Hill
The University of North Carolina at Chapel Hill
Swanstrom, Ronald I.
United States, Chapel Hill
The University of North Carolina at Chapel Hill
Morris, Lynn
South Africa, Johannesburg
National Institute for Communicable Diseases
Statistics
Citations: 71
Authors: 5
Affiliations: 2
Identifiers
Doi:
10.1016/j.virol.2006.07.030
ISSN:
00426822
e-ISSN:
10960341
Research Areas
Genetics And Genomics
Infectious Diseases