Comparisons of the genetic and neutralization properties of HIV-1 subtype C and CRF07/08_BC env molecular clones isolated from infections in China

Abstract

Subtype C is the most prevalent HIV-1 subtype globally and a common circulating recombinant form virus, CRF_BC, is predominant in China. It is unclear whether subtype C-based vaccines are capable of neutralizing CRF_BC viruses or can be evaluated using a neutralization assay based on CRF_BC pseudoviruses. Phylogenetic analysis of full-length gp160 nucleotide sequences showed that 37 functional env clones formed two unique clusters. The 30 clones belonged to 07_BC and seven clones 08_BC. Increased length in gp120 was found in 07_BC clones when compared to subtype C and 08_BC clones. The subtype BC clones had more PNLG sites on gp160, and 08_BC had more PNLG sites in the V5 region than subtype C. However, the number of PNLG sites in the C4 region of 07_BC was less than subtype C. The neutralization properties of Env-pseudovirus were analyzed against HIV-positive plasma panels belonging to three subtypes: BC, B and AE. Subtype BC pseudoviruses had higher sensitivities to all the three plasma panels than subtype C viruses. CRF07_BC clones were the most sensitive to subtype BC antibodies, regardless of whether the CRF07_plasma panel or CRF08_BC were used. Heatmap analyses of inhibition ratios showed that clones in this study were antigenically diverse despite being genetic similarity. Thus, genetic and neutralization properties of HIV CRF07/08_BC Env isolates predominating in China show different properties than those of subtype C. These findings are likely to provide useful information for the design and evaluation of HIV-1 neutralizing antibody-based vaccine development in China.