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• W2235528251 abstract "HIV-1 gains entry into host cells by binding to CD4 and a coreceptor, predominantly CCR5 or CXCR4. Viruses that use CCR5 are termed R5, those able to use CXCR4 are termed X4 while viruses able to use both coreceptors are referred to as R5X4. Accelerated CD4 decline and disease progression within an infected HIV-1 subtype B infected individual is often associated with the emergence of viruses able to use CXCR4. However, CXCR4 coreceptor usage appears to occur less frequently among HIV-1 subtype C viruses, the most predominant strain circulating globally, including South Africa. The aim of this study was to investigate the genetic determinants of CXCR4 usage in HIV-1 subtype C isolates. The V3 region of the envelope glycoprotein is the major determinant of coreceptor usage. In Chapter 2, 32 subtype C isolates with known phenotypes (16 R5, 8 R5X4 and 8 X4 isolates) were assessed using a subtype C specific V3-heteroduplex tracking assay. Results indicated that there were sufficient genetic differences to discriminate between R5 viruses and those able to use CXCR4 (both R5X4 and X4). In general, R5 isolates had a mobility ratio >0.9 whereas CXCR4-using isolates were usually <0.9. 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). Thus, the rare occurrence of CXCR4-using viruses in subtype C may be due to the highly conserved" @default.
• W2235528251 created "2016-06-24" @default.
• W2235528251 creator A5065740534 @default.
• W2235528251 date "2006-10-31" @default.
• W2235528251 modified "2023-09-27" @default.
• W2235528251 title "In vitro and in vivo diversity of HIV-1 subtype C envelope proteins and correlation with changes in biological properties of viral isolates." @default.
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