Recombinant HIV type 1 gp41 Antigen, Detection [ENV124]

CRF01_AE is one of the four dominant HIV-1 strains circulating in China. In this study, we performed genetic and phenotypic analyses using a total of 60 full-length envelope gene clones from 14 HIV-1-infected individuals in the Beijing area. Among the 60 sequences analyzed, 32 have a complete open reading frame (ORF), whereas the others contain premature stop codons. The phylogenetic tree analysis suggested that all of the sequences maintained a close relationship with the CRF01_AE strain. Most of the potential N-linked glycosylation sites (PNGS) were located within the V1/V2, V4, C2, or C3 regions. In relation to gp41, the majority of the glycosylation sites were located in the ectodomain. The 32 env genes that contained intact ORFs were used to construct Env-pseudotyped viruses, and eight strains that resulted in high titers were further studied. All the eight strains used CCR5 as the co-receptor for infection, and they were sensitive to neutralization by the broadly neutralizing monoclonal antibodies, including VRC_01, PG9, PG16, and NIH45-46, but they were insensitive to 2G12. Notably, seven of these eight strains lacked a glycan at residues 295 or 332 (or both), suggesting that these two PNGSs play an important role in 2G12 binding and neutralization. In addition, the pseudoviruses were more sensitive to neutralization by plasma isolated from individuals infected with subtypes CRF01_AE and CRF07/08_BC, suggesting the occurrence of a cross-neutralizing antibody profile between these two strains. These findings are likely to have important implications for the design of an effective HIV vaccine and relevant therapeutic drugs.

Background: Few HIV-1fusion and replication inhibitors were developed, with limited clinical applications because of their short half-life, drug resistance and cross-reactivity with preexisting antibodies in HIV-infected patients. Objective: These limitations call for new strategies in the development of next anti-HIV-1 drugs. Among anti-gp41HIV-1 inhibitors, short-peptides exhibit high antiviral activity but the mechanism of action at molecular level has not been sufficiently addressed. Method: We report potent QSAR (Quantitative Structure-Activity Relationship) models, used for biological activity prediction of novel short HIV-1 gp41 inhibitor peptides in order to: (i) validate the anti-HIV-1 activity of MT-sifuvirtide, MT-SC34EK, MT-C34 and HP23, expressed as IC50fusion and IC50replication; (ii) predict inhibitory activity of SC24EK and its MT-derivative expressed as IC50resistant (HIV-1 NL4-3 variant); (iii) propose new derivatives DMT-SC22EK, DMT-SC29EK and DMT-sifuvirtide through addition of aspartic acids by induced-mutagenesis; (iv) use molecular similarity established by fingerprint models to correlate molecular spatial features with predicted biological activity of newly generated inhibitors over parent compounds. Results: We obtained good QSAR statistic parameters, demonstrating that our QSAR models are able to predict biological activity of new HIV-1 inhibitors with suitable accuracy. Conclusion: Despite acknowledged drawbacks of a reduced dataset, our results may enhance the evaluation of biological activity of new and classical synthetic peptides as anti-HIV- 1 agents and represent a good start for further studies in developing new antiviral drugs.