Genotypic Characterization of CRF01_AEenvGenes Derived from Human Immunodeficiency Virus Type 1-Infected Patients Residing in Central Thailand

Abstract

CRF01_AE is a major subtype of human immunodeficiency virus type 1 (HIV-1) circulating in Southeast Asia, including Thailand. HIV-1 env genes were amplified by polymerase chain reaction from blood samples of HIV-1-infected patients residing in Thailand in 2006, and cloned into the pNL4-3-derived reporter viral construct. Generated envelope protein (Env)-recombinant virus was examined for its infectivity, and then 35 infectious CRF01_AE Env-recombinant viruses were selected. Sequencing analysis revealed that the interclone variation of the deduced amino acid sequences was higher in CRF01_AE env genes isolated in 2006 than in those isolated in the early 1990s, suggesting that env gene variation has been increasing gradually among CRF01_AE viruses prevalent in Thailand. We also examined the characteristics of the deduced amino acid sequences of 35 CRF01_AE env genes. Our results may provide useful information to help in better understanding the genotype of env genes of CRF01_AE viruses currently circulating in Thailand.

Molecular Evolution of the HIV-1 Thai Epidemic between the Time of RV144 Immunogen Selection to the Execution of the Vaccine Efficacy Trial

“…Regarding the level of genetic diversity among full-genome CRF01_AE sequences in RV148, we noticed increases of 31% and 24% compared to the measurements from Thailand from 1990 to 1999 and 2000 to 2004, respectively. This observation supports previous observations indicating that in the past 2 decades the CRF01_AE Thai epidemic has experienced a continued genetic expansion (25). The proportion of RV148 strains that were subtype B was 3.5%.…”

“…First, it was noted that the withinsubtype interhost genetic divergence had increased significantly compared to that noted in earlier surveys (9,10,17,(22)(23)(24)(25). Second, the barriers that maintained the segregation of subtypes on the basis of risk factors started to efface; the representation of CRF01_AE among IDUs increased, especially among new infections (26), to the point where CRF01_AE accounted for 80 to 90% of the cases in Bangkok and the northern province of Chiang Mai (27,28).…”

Two N-Linked Glycosylation Sites in the V2 and C2 Regions of Human Immunodeficiency Virus Type 1 CRF01_AE Envelope Glycoprotein gp120 Regulate Viral Neutralization Susceptibility to the Human Monoclonal Antibody Specific for the CD4 Binding Domain

“…Two CRF01_AE Env clones, 65CC1 and 65CC4, showed distinct neutralization susceptibility to b12 (47), although these CRF01_AE Env clones had a close phylogenetic relationship (46). In addition, our previous results suggested that the determinants of b12 resistance of 65CC4 were located within the N-terminal regions (C1, V1, V2, C2, V3, and a 36-amino-acid sequence of C3 before the XbaI recognition site) of Env gp120 (47).…”

“…Recent studies on CRF01_AE (40,47) and subtype C Env (39) showed that viral susceptibility to neutralizing antibodies was inversely correlated with the length of V1 and V2 regions of Env gp120. In addition, several CRF01_AE Env clones that contain a long V2 region, similar to 65CC1 (46), were resistant to b12-mediated neutralization (47). Thus, we considered that short V1 and V2 regions of 65CC4 might not account for the lower b12 susceptibility of 65CC4 compared to 65CC1.…”

“…Recently, we established 35 infectious CRF01_AE Env recombinant viruses, and studied their neutralization susceptibility to neutralizing human monoclonal antibodies, patient serum and HIV-1 entry inhibitors (46,47). Among them, a recombinant virus containing CRF01_AE Env, 65CC1 was susceptible to b12, while 34 remaining CRF01_AE Env recombinant viruses, including the virus containing CRF01_AE Env, 65CC4, were resistant to b12 (47).…”