title: Genetic and Phenotypic Analysis of CRF01_AE HIV-1 env Clones from Patients Residing in Beijing, China.
abstract: 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.
authors.affiliation: 1 College of Life Science and Bioengineering, Beijing University of Technology , Beijing, China .|2 Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University , Beijing, China .
authors.forename: Danying
authors.initials: D
authors.lastname: Chen
authors.affiliation: 3 State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Viral Disease Control and Prevention , China CDC, Beijing, China .
authors.forename: Xiaozhou
authors.initials: X
authors.lastname: He
authors.affiliation: 4 Beijing Center for Disease Prevention and Control , Beijing, China .
authors.forename: Jingrong
authors.initials: J
authors.lastname: Ye
authors.affiliation: 1 College of Life Science and Bioengineering, Beijing University of Technology , Beijing, China .
authors.forename: Pengxiang
authors.initials: P
authors.lastname: Zhao
authors.affiliation: 1 College of Life Science and Bioengineering, Beijing University of Technology , Beijing, China .|3 State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Viral Disease Control and Prevention , China CDC, Beijing, China .
authors.forename: Yi
authors.initials: Y
authors.lastname: Zeng
authors.affiliation: 3 State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Viral Disease Control and Prevention , China CDC, Beijing, China .
authors.forename: Xia
authors.initials: X
authors.lastname: Feng
mesh_terms: D000293:Adolescent; D000328:Adult; D057134:Antibodies, Neutralizing / Q000276:immunology; D000068476:Beijing; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006031:Glycosylation; D015483:HIV Antibodies / Q000276:immunology; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009500:Neutralization Tests; D010641:Phenotype; D010802:Phylogeny; D019713:Receptors, CCR5 / Q000378:metabolism; D015728:Receptors, HIV / Q000378:metabolism; D017422:Sequence Analysis, DNA; D053585:Virus Attachment; D055815:Young Adult; D054299:env Gene Products, Human Immunodeficiency Virus / Q000235:genetics
chemical_list: D057134:Antibodies, Neutralizing; C584933:CCR5 protein, human; D015483:HIV Antibodies; D019713:Receptors, CCR5; D015728:Receptors, HIV; D054299:env Gene Products, Human Immunodeficiency Virus
keywords: CRF01_AE; China; HIV-1; env; genetic analysis; phenotypic analysis