Critical amino acid residues and potential N-linked glycosylation sites contribute to circulating recombinant form 01_AE pathogenesis in Northeast China

AIDS. 2019 Jul 15;33(9):1431-1439. doi: 10.1097/QAD.0000000000002197.

Abstract

Objective: The current study aimed to understand epidemiological feature and critical factors associated with pathogenesis of circulating recombinant form (CRF) 01_AE strains in Northeast China.

Design: Compared analysis was made between CRF01_AE and non-CRF01_AE samples to understand the pathogenicity features of CRF01_AE. Further analyses between CRF01_AE samples with high or low CD4 cell counts and between samples with different coreceptor usages were done to explore the possible factors correlating to the pathogenesis of CRF01_AE viruses.

Methods: The genotypes of newly identified strains were determined by phylogenetic analyses using Mega 6.06. Coreceptor usage was predicted by Geno2Pheno algorithm. Potential N-linked glycosylation site (PNGS) number was calculated using the online N-glycosite software. The properties of amino acid sequences were analyzed by the online ProtParam tool.

Results: CRF01_AE become the main HIV-1 genotype since 2010. Compared with non-CRF01_AE group, the CRF01_AE group showed a higher proportion of samples with CD4 cell count less than 200 cells/μl. Shorter amino acid length, fewer PNGSs and the presence of a basic motif R/KNXT or NR/KT in V4 correlated to a lower CD4 cell count, and existence or coexistence of Thr12, Arg13, Val21 and Lys33, presence of more than 4 of net charges and lack of the PNGS within V3 favored to the X4/R5X4 coreceptor usage of CRF01_AE viruses.

Conclusion: CRF01_AE has dominated HIV-1 genotype in Northeast China. Infection with CRF01_AE exhibited a fast disease progression, which may be associated with specific amino acid residues and PNGSs in V3 and V4 regions as well as amino acid length of V4 region.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • China
  • Genetic Variation
  • Genotype*
  • Glycosylation*
  • HIV Envelope Protein gp120 / genetics*
  • HIV Envelope Protein gp120 / metabolism
  • HIV Infections / physiopathology*
  • HIV Infections / virology*
  • HIV-1 / classification
  • HIV-1 / genetics*
  • HIV-1 / pathogenicity*
  • Humans
  • Phylogeny

Substances

  • HIV Envelope Protein gp120