Transmitted/Founder HIV-1 Subtype C Viruses Show Distinctive Signature Patterns in Vif, Vpr, and Vpu That Are Under Subsequent Immune Pressure During Early Infection

AIDS Res Hum Retroviruses. 2016 Oct/Nov;32(10-11):1031-1045. doi: 10.1089/AID.2015.0330. Epub 2016 Jul 26.

Abstract

Viral variants that predominate during early infection may exhibit constrained diversity compared with those found during chronic infection and could contain amino acid signature patterns that may enhance transmission, establish productive infection, and influence early events that modulate the infection course. We compared amino acid distributions in 17 patients recently infected with HIV-1C with patients with chronic infection. We found significantly lower entropy in inferred transmitted/founder (t/f) compared with chronic viruses and identified signature patterns in Vif and Vpr from inferred t/f viruses. We investigated sequence evolution longitudinally up to 500 days postseroconversion and compared the impact of selected substitutions on predicted human leukocyte antigen (HLA) binding affinities of published and predicted cytotoxic T-lymphocyte epitopes. Polymorphisms in Vif and Vpr during early infection occurred more frequently at epitope-HLA anchor residues and significantly decreased predicted epitope-HLA binding. Transmission-associated sequence signatures may have implications for novel strategies to prevent HIV-1 transmission.

Keywords: CTL epitope; HIV transmission; Vif; Vpr; Vpu; accessory genes; evolution.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amino Acid Sequence
  • Epitopes / genetics
  • Evolution, Molecular
  • Female
  • Genotype
  • HIV Infections / transmission*
  • HIV Infections / virology*
  • HIV-1 / genetics*
  • HIV-1 / immunology
  • HIV-1 / isolation & purification
  • Human Immunodeficiency Virus Proteins / genetics*
  • Humans
  • Longitudinal Studies
  • Male
  • Selection, Genetic*
  • Viral Regulatory and Accessory Proteins / genetics*
  • vif Gene Products, Human Immunodeficiency Virus / genetics*
  • vpr Gene Products, Human Immunodeficiency Virus / genetics*

Substances

  • Epitopes
  • Human Immunodeficiency Virus Proteins
  • Viral Regulatory and Accessory Proteins
  • vif Gene Products, Human Immunodeficiency Virus
  • vif protein, Human immunodeficiency virus 1
  • vpr Gene Products, Human Immunodeficiency Virus
  • vpr protein, Human immunodeficiency virus 1
  • vpu protein, Human immunodeficiency virus 1