Basic Research
Neutralization sensitivity and immune escape of HIV-1 CNS related mutations
Ouyang Yabo, Wang Chen, Zhang Dai, Sun Jianping, Hou Jiali, Qiao Luxin, Yang Yang, Zhang Yulin, Chen Dexi, Ren Li, Ma Liying
Published 2019-08-25
Cite as Int J Virol, 2019, 26(4): 272-276. DOI: 10.3760/cma.j.issn.1673-4092.2019.04.016
Abstract
ObjectiveTo investigate neutralization sensitivity of HIV-1 pseudoviruses with CNS related mutations on broadly monoclonal neutralizing antibodies (bmNAbs), and to explore the possibility of immune escape.
MethodsThe pseudoviruses with HIV-1 CNS related mutations, including S446T, F396N, K429G, K337G, T319A, Q389K and N407T were constructed. The corresponding infectivity of above mutants, and the neutralization sensitivity in responding to bmNAbs, e.g. PGT121、PGT135、VRC01、2G12、10E8 and 12A21 were determined. Molecular docking was used to explore the effects of CNS-related residues of env proteins on antibody binding.
ResultsAll the pseudoviruses carrying 7 mutations were highly sensitive to neutralization by VRC01, 2G12 and 10E8, but were resistant to PGT121 and 12A21. As for PGT135, the pseudovirus containing the F396N mutant displayed highly sensitive to it, and S446T, K429G and T319A mutants showed moderately sensitive to this mutation type, but K337G, Q389K and N407T were resistant to PGT135. When the molecular conformational simulation of Q389 mutated to K, the hydrogen bond formed between the nitrogen atom of Q389 NE2 and the oxygen atom of T415 disappeared. The folding of the amino acid side chain may strengthen in steric hindrance, affecting the residue at position 389 as a contactable residue to interaction with PGT135.
ConclusionsHIV-1 pseudovirus with CNS-related mutations may undergo immune escape, which reduced neutralization sensitivity to PGT135 in some degree..
Key words:
HIV-1; CNS; gp120; immune escape; neutralization
Contributor Information
Ouyang Yabo
Beijing Institute of Hepatology, Beijing You’an Hospital, Capital Medical University, Beijing 100069, China
Wang Chen
National Center for AIDS/STD Control and Prevention (NCAIDS), Chinese Center for Disease Control and Prevention, Beijing 102206, China
Zhang Dai
National Center for AIDS/STD Control and Prevention (NCAIDS), Chinese Center for Disease Control and Prevention, Beijing 102206, China
Sun Jianping
Biomarkers of infection related diseases Beijing key laboratory, Beijing You’an Hospital, Capital Medical University, Beijing 100069, China
Hou Jiali
National Center for AIDS/STD Control and Prevention (NCAIDS), Chinese Center for Disease Control and Prevention, Beijing 102206, China
Qiao Luxin
Beijing Institute of Hepatology, Beijing You’an Hospital, Capital Medical University, Beijing 100069, China
Yang Yang
Beijing Institute of Hepatology, Beijing You’an Hospital, Capital Medical University, Beijing 100069, China
Zhang Yulin
Beijing Institute of Hepatology, Beijing You’an Hospital, Capital Medical University, Beijing 100069, China
Chen Dexi
Beijing Institute of Hepatology, Beijing You’an Hospital, Capital Medical University, Beijing 100069, China
Ren Li
National Center for AIDS/STD Control and Prevention (NCAIDS), Chinese Center for Disease Control and Prevention, Beijing 102206, China
Ma Liying
National Center for AIDS/STD Control and Prevention (NCAIDS), Chinese Center for Disease Control and Prevention, Beijing 102206, China
