title: Association of variations of NAb 2F5 and 4E10 epitopes and disease progression in Chinese antiretroviral treatment-naïve patients infected with HIV-1 clade B'.
abstract: BACKGROUND
  Studies on human immunodeficiency virus type 1 (HIV-1) vaccines have recently focused on targeting the conserved neutralizing epitopes 2F5 and 4E10, and hence it is important to understand the extent of mutations in these two viral epitopes. Here, we investigated the amino acid mutations in epitopes of 2F5 (ELDKWA, HIV-1 HXB2 env 662 - 667 aa) and 4E10 (NWFDIT, HIV-1 HXB2 env 671 - 676 aa) in the membrane proximal-external region of gp41 from clade B' HIV-1-infected individuals living in Henan province, China. We also examined the frequency of a mutation and its relation to disease progression.
  
  
  METHODS
  A cohort of 54 treatment-naïve HIV-1-infected individuals was recruited in this study, and 16 individuals were selected for a short-term longitudinal study on sequence evolution. The HIV-1 env gp41 gene was amplified, cloned, and sequenced, and predicted amino acid sequences were aligned for analysis.
  
  
  RESULTS
  The mutations E662A and K665E on the 2F5 epitope and N671S and T676S on the 4E10 epitope were seen. Simultaneous RNA sequencing showed some discrepancies with proviral DNA sequences. In our longitudinal study, mutation levels of these two neutralizing epitopes were low but diverse and persistent. The frequencies of mutations within the 4E10 peptide NWFDIT in slow progressors were noticeably lower than those in AIDS patients (P < 0.05).
  
  
  CONCLUSIONS
  Antigenic variation of the neutralizing epitopes 2F5 and 4E10 is limited in subtype B' infection, and that 4E10 peptide mutation is correlated with disease progression. Monitoring epitope mutations will offer useful data for development of the candidate 2F5-like and 4E10-like antibodies to prevent and treat AIDS.
authors.affiliation: Key Laboratory of Immunology of AIDS, Ministry of Health, First Affiliated Hospital, China Medical University, Shenyang, Liaoning 110001, China.
authors.forename: Xiao-Li
authors.initials: XL
authors.lastname: Zhang
authors.forename: Xiao-Xu
authors.initials: XX
authors.lastname: Han
authors.forename: Di
authors.initials: D
authors.lastname: Dai
authors.forename: Ming-Jia
authors.initials: MJ
authors.lastname: Bao
authors.forename: Dong-Bing
authors.initials: DB
authors.lastname: Xu
authors.forename: Zi-Ning
authors.initials: ZN
authors.lastname: Zhang
authors.forename: Ya-Nan
authors.initials: YN
authors.lastname: Wang
authors.forename: Min
authors.initials: M
authors.lastname: Zhao
authors.forename: Tristan
authors.initials: T
authors.lastname: Bice
authors.forename: Yong-Jun
authors.initials: YJ
authors.lastname: Jiang
authors.forename: Hong
authors.initials: H
authors.lastname: Shang
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy*; D000328:Adult; D057134:Antibodies, Neutralizing / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D018450:Disease Progression; D000939:Epitopes / Q000235:genetics*; D019143:Evolution, Molecular; D015483:HIV Antibodies / Q000235:genetics*; D015700:HIV Envelope Protein gp41 / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008137:Longitudinal Studies; D008875:Middle Aged; D009154:Mutation; D012367:RNA, Viral / Q000097:blood / Q000737:chemistry
chemical_list: D057134:Antibodies, Neutralizing; D000939:Epitopes; D015483:HIV Antibodies; D015700:HIV Envelope Protein gp41; D012367:RNA, Viral; C514787:gp41 protein, Human immunodeficiency virus 1