Association of variations of NAb 2F5 and 4E10 epitopes and disease progression in Chinese antiretroviral treatment-naïve patients infected with HIV-1 clade B

• Published in: Chinese medical journal 2010-12, Vol.123 (23), p.3406-3411
• Main Authors: Zhang, Xiao-Li, Han, Xiao-Xu, Dai, Di, Bao, Ming-Jia, Xu, Dong-Bing, Zhang, Zi-Ning, Wang, Ya-Nan, Zhao, Min, Bice, Tristan, Jiang, Yong-Jun, Shang, Hong
• Format: Article
• Language: English
• Subjects: Acquired Immunodeficiency Syndrome - drug therapy; Adult; Antibodies, Neutralizing - genetics; Asian Continental Ancestry Group - genetics; Disease Progression; Epitopes - genetics; Evolution, Molecular; HIV Antibodies - genetics; HIV Envelope Protein gp41 - immunology; HIV-1 - immunology; Humans; Longitudinal Studies; Middle Aged; Mutation; RNA, Viral - blood; RNA, Viral - chemistry
• ISSN: 0366-6999
• DOI: 10.3760/cma.j.issn.0366-6999.2010.23.006

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. 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. 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). 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.