Genetic and Neutralization Sensitivity of Diverse HIV-1 env Clones from Chronically Infected Patients in China

Abstract

As HIV-1 continues to spread in China from traditional high risk populations to the general public, its genetic makeup has become increasingly complex. However, the impact of these genetic changes on the biological and neutralization sensitivity of the virus is unknown. The current study aims to characterize the genetic, biological, and neutralization sensitivity of HIV-1 identified in China between 2004 and 2007. Based on a total of 107 full-length envelope genes obtained directly from the infected patients, we found that those viruses fell into three major genetic groups: CRF01_AE, subtype B, and subtype C/CRF07_BC/CRF08_BC/BC. Pseudotyped viruses built upon the viable env genes have demonstrated their substantial variability in mediating viral entry and in sensitivity to neutralization by subtype-specific plasma pools and broadly neutralizing monoclonal antibodies (bnmAb). Many viruses are resistant to one or more bnmAb, including those known to have high potency against diverse viruses from outside China. Sequence and structural analysis has revealed several mechanisms by which these resistant viruses escape recognition from bnmAb. We believe that these results will help us to better understand the impact of genetic diversity on the neutralizing sensitivity of the viruses and to facilitate the design of immunogens capable of eliciting antibodies with potency and breadth similar to those of bnmAb.

Broad Antiviral Activity and Crystal Structure of HIV-1 Fusion Inhibitor Sifuvirtide

“…It is know that the Env genes of CRF01_BC originate from the subtype C viruses, but some studies indicate that this recombinant form of virus has unique biological characteristics (44 -46). For example, it is found that CRF01_BC strains exclusively use CCR5 co-receptor for infection and are highly resistant to the known broadly neutralizing antibodies (44,45). With the second large panel of HIV-1 pseudoviruses corresponding to the CRF07_BC, CRF01_AE, and BЈ subtypes, SFT consistently shows its potency to overcome the genetic diversity.…”

Human Blood-Circulating Basophils Capture HIV-1 and Mediate Viraltrans-Infection of CD4+T Cells

“…HIV-like particles (VLPs) was generated by cotransfecting HEK293T cells with a plasmid containing Gag-green fluorescent protein (Gag-GFP) and plasmids expressing JRFL, HXB2, and CNE3 (CCR5-tropic) HIV envelope proteins as reported previously (62). The plasmid expressing CNE3 envelope protein, cloned from an HIV-1 isolate circulating in China (63), was provided by Lin-Qi Zhang (Tsinghua University, China). The replication-competent HIV-1-AD8 (CCR5-tropic) virus was produced by transfection with the pNLAD8 vector containing HIV-1 proviral DNA.…”

CCR5 Antagonist TD-0680 Uses a Novel Mechanism for Enhanced Potency against HIV-1 Entry, Cell-mediated Infection, and a Resistant Variant

“…First, TD-0232 and TD-0680 were tested in a single-cycle infectivity assay using GHOST(3)-CD4-CCR5 cells against a panel of genetically diverse R5-tropic HIV-1 and SIV Env-pseudotyped viruses, including primary Envs derived from six chronically infected Chinese patients (CNE, Chinese Env) (29). As summarized in Table 1, TD-0680 was found to be the most potent, with broad inhibitory activities against multiple HIV-1 subtypes.…”