Molecular Characteristics of the Envelope of Vertically Transmitted HIV-1 Strains from Infants with HIV Infection

AIDS Res Hum Retroviruses. 2017 Aug;33(8):796-806. doi: 10.1089/AID.2016.0260. Epub 2017 Jun 19.

Abstract

Mother-to-child transmission (MTCT) of HIV offers a good opportunity to study the dynamics of early viral evolution in the host environment to which the virus has partially adapted. Such studies would throw light on the unique features of the infecting viruses, which will subsequently help to design preventive or therapeutic measures against the newly infecting and evolving strains of HIV. Therefore, we undertook a study to determine the genetic divergence of proviral envelope sequences from the HIV-infected infants (<2 years). Detailed analysis revealed unique features of potential N-linked glycosylation sites (PNGS) and their frequency of occurrence that built on the difference in length of the V1V2 region of the envelope sequences. Surprisingly, frequency of PNGS in the V5 region was found to revert rapidly, in about 75% of the sequences, which could surmise a fitness disadvantage in the variant forms. Further, a stable net charge was observed in the V2 and V3 regions prompting us to speculate on the established interaction of the transmitted variant with the integrin α4β7 receptor and R5 co-receptor, respectively. In brief, our observations suggest that differences in the length of the variable regions and variation in the frequency of PNGS in the envelope of the viruses obtained from very recently infected individuals in our population could be important characteristics of the unique quasispecies that is responsible for the spread of HIV in the early stages of infection in MTCT.

Keywords: PNGS; infectivity fitness; variable region; vertical HIV-1 transmission; viral tropism.

MeSH terms

  • Female
  • Genetic Variation
  • Glycosylation
  • HIV Infections / transmission*
  • HIV Infections / virology*
  • HIV-1 / classification
  • HIV-1 / genetics*
  • Humans
  • Infant
  • Infectious Disease Transmission, Vertical*
  • Male
  • Prospective Studies
  • Proviruses / classification
  • Proviruses / genetics*
  • Sequence Analysis, DNA
  • env Gene Products, Human Immunodeficiency Virus / genetics*

Substances

  • env Gene Products, Human Immunodeficiency Virus