Molecular evolution and consensus sequence research of HIV CRF01_AE subtype and its related recombinant subtype envelope glycoprotein in China(2015-2021)
Objective To understand the molecular epidemiology of HIV CRF01_AE subtype and its related recombinant subtype envelope glycoprotein(ENV)in China,and to establish ENV consensus sequences to analyze amino acid mutations and protein tertiary structure.Methods Full-length ENV gene sequences of HIV-1 CRF01_AE subtype and related recombinant subtypes in China from 2015 to 2021 were collected from the Los Alamos database.A phylogenetic evolutionary tree was constructed,and ENV consensus sequences were established.Protscale and PROVEAN were used to predict changes in amino acid hydrophobicity in broad neutralizing antibody epitopes of the ENV consensus sequence and harmful mutations,and the impact of amino acid mutations on the tertiary structure of the ENV protein was analyzed.Results Phylogenetic analysis showed that 70.0％(14/20)of CRF01_AE subtype sequences belonged to evolutionary cluster 4.In the broad neutralizing antibody epitope V1/V2 and Loop D of the ENV consensus sequence,there were 4 and 1 amino acid mutations,respectively,causing changes in hydrophobicity.PROVEAN predicted that the mutations G152D at the V1/V2 and M476I at the β23/V5/β24 epitopes were harmful.The protein tertiary structure pLDDT value of the ENV consensus sequence was 86.2,with a new α helices generated in the V1/V2 epitope due to harmful mutations.Conclusions The genetic lineage of HIV-1 CRF01_AE subtype in China is diverse,contributing to the formation of recombinant viruses.Amino acid mutations in the V1/V2 structural domain of the ENV consensus sequence result in changes in its protein spatial structure,which may impact the subsequent induction of broad neutralizing antibodies.
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