Journal
JOURNAL OF MEDICAL VIROLOGY
Volume 78, Issue 5, Pages 523-534Publisher
WILEY
DOI: 10.1002/jmv.20572
Keywords
evolution; recombination; replication; CRF02-AG; Cameroon
Categories
Funding
- FIC NIH HHS [TW01254, TW01409] Funding Source: Medline
- NIAID NIH HHS [5P30 AI 27742, AI47053] Funding Source: Medline
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Human immunodeficiency virus type 1 (HIV-1) circulating recombinant form (CRF) 02(-)AG is the predominant subtype in Cameroon, even more prevalent than the parental subtypes A and G. An important question that needs to be addressed is whether recombination in HIV-1 infection can lead to the emergence of viruses with biological advantages. The replicative capacity was investigated in peripheral blood mononuclear. cells (PBMCs) of 13 R5-tropic primary HIV-1 isolates, including 5 CRF02(-)AG, 4 subtype A, and 4 subtype G viruses. HIV-1 subtype identity was defined by phylogeny either of the full-length genome or analysis of a combination of segments of the gag, pro, pol, and envgenes followed by recombination breakpoint analysis. All viruses were grown on PBMCs for 11 days and culture supernatant was analyzed for reverse transcriptase (RT) activity and p24 production. On day 11 post-infection, CRF02(-)AG strains had a 1.4-1.9 times higher RT activity and reached a significantly higher level of p24 production than the parental subtypes A and G. Furthermore, the replication rate as measured by p24 production was 1.4 times higher for CRF02(-)AG strains compared to the subtypes A and G. This study suggests that the recombination event that led to CRF02_AG resulted in a variant with a better replicative capacity than its progenitors. This adaptation could contribute to the broader spread of HIV-1 CRF02_AG leading to its predominance in West Central Africa compared to the lower prevalence of its parental subtypes A and G. (c) 2006 Wiley-Liss, Inc.
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