Phenotypic and genotypic characterization of Human Immunodeficiency Virus type 1 CRF07_BC strains circulating in the Xinjiang Province of China

Abstract

BackgroundHIV-1 CRF07_BC recombinant previously circulated mainly among the intravenous drug users (IDUs) in Xinjiang province of China and is currently spreading in the entire country. The aim of this study is to characterize the genotypic and phenotypic properties of HIV-1 CRF07_BC isolates in comparison with those of the subtype B' (Thailand B) which is prevalent in the former plasma donors (FPDs) in China.ResultsTwelve HIV-1 CRF07_BC variants were isolated from the blood of the HIV-1-infected IDUs in Xinjiang province, and 20 subtype B' isolates were obtained from the FPDs in Anhui and Shanxi provinces of China. All the CRF07_BC viruses utilized CCR5 co-receptor, whereas 12 subtype B' viruses were R5-tropic, and the remaining B' isolates were dual (R5X4) tropic. CRF07_BC viruses had lower net charge value in the V3 loop and exhibited slower replication kinetics than subtype B' viruses. The number and location of the potential N-linked glycosylation sites in V1/V2 and the C2 region of the CRF07_BC viruses were significantly different from those of the subtype B' viruses.ConclusionThe HIV-1 CRF07_BC recombinant strains with relatively lower net charges in the V3 loop exclusively utilize CCR5 co-receptor for infection and exhibit slow replication kinetics in the primary target cells, suggesting that CRF07_BC may be superior over B' and other HIV-1 subtypes in initiating infection in high-risk population. These findings have molecular implications for the adaptive evolution of HIV-1 circulating in China and the design of tailored therapeutic strategy for treatment of HIV-1 CRF07_BC infection.

In Vitro Infection of Human Umbilical Cord Blood CD34+ Hematopoietic Progenitor Cells by HIV-1 CRF07_BC Enveloped Pseudovirus

“…Consistent with previous reports, 2.3~15.6% and 0~1.9% expressed CD4 and CXCR4 or CD4 and CCR5 respectively. The low expression of CCR5 co-receptor on HPCs may explain the limited infection efficacy, ~0.86% observed in our experiments, since it was reported [25] that the cell tropisms of primary isolates of subtype B/C from Chinese HIV-1 infected patients only used CCR5 as the co-receptor. While the expression of CD4, CCR5 and CXCR4 on HPCs enables these cells as potential targets for HIV-1 infection, however, CCR5 ligands, including MIP-1 , MIP-1 , and RANTES, as well as CXCR4 ligand SDF-1 secreted by CD34 + HPCs [26][27][28], could compete with HIV-1 and thereby block the entry of HIV-1 into HPCs.…”

Enfuvirtide−PEG conjugate: A potent HIV fusion inhibitor with improved pharmacokinetic properties

“…The sources of HIV-1 SF33 and TZM-bl, as well as the methods used for their preservation and passage have been described previously [20,41]. The clinical isolates of HIV-1 subtypes B 0 , BC, and AE were obtained from treatment-naive patients and stored at our laboratory in Chinese Center for Disease Control and Prevention [46,47]. These viruses represent the predominant strains circulating in China from 2005 to 2008.…”

Profiling the neutralizing antibody response in chronically HIV-1 CRF07_BC-infected intravenous drug users naïve to antiretroviral therapy

“…Median CD4 counts and plasma viral loads at the time of sampling were 378 cells/mm 3 (full range: 50–940 cells/mm 3 ) and 20,700 copies/ml (full range: <50–714,000 copies/ml), respectively (Table S1). Subjects became infected through sharing contaminated needles during drug use, and subjects were confirmed to be infected with CRF07_BC strain162526 (Table S1). The historical neutralization data of 103 subjects from the FPD cohort15 with over ten years’ infection time were used to compare with those generated in the IDU cohort.…”

“…Our laboratory previously studied the biological and virological characteristics25 and cytotoxic T lymphocyte (CTL) response pattern26 of CRF07_BC infection. However, the humoral response pattern during infection caused by this unique recombinant subtype has not yet been adequately investigated.…”