Genetic and phenotypic analyses of sequential vpu alleles from HIV-infected IFN-treated patients

Virology. 2017 Jan;500:247-258. doi: 10.1016/j.virol.2016.10.028. Epub 2016 Nov 15.

Abstract

Treatment of HIV-infected patients with IFN-α results in significant, but clinically insufficient, reductions of viremia. IFN induces the expression of several antiviral proteins including BST-2, which inhibits HIV by multiple mechanisms. The viral protein Vpu counteracts different effects of BST-2. We thus asked if Vpu proteins from IFN-treated patients displayed improved anti-BST-2 activities as compared to Vpu from baseline. Deep-sequencing analyses revealed that in five of seven patients treated by IFN-α for a concomitant HCV infection in the absence of antiretroviral drugs, the dominant Vpu sequences differed before and during treatment. In three patients, vpu alleles that emerged during treatment improved virus replication in the presence of IFN-α, and two of them conferred improved virus budding from cells expressing BST-2. Differences were observed for the ability to down-regulate CD4, while all Vpu variants potently down-modulated BST-2 from the cell surface. This report discloses relevant consequences of IFN-treatment on HIV properties.

Keywords: BST-2; Evolution; HIV-1; Interferon; Restriction factor; Vpu.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Antigens, CD / genetics
  • Antigens, CD / metabolism
  • CD4 Antigens / genetics
  • CD4 Antigens / metabolism
  • GPI-Linked Proteins / genetics
  • GPI-Linked Proteins / metabolism
  • HIV Infections / drug therapy*
  • HIV Infections / virology*
  • HIV-1 / classification
  • HIV-1 / genetics*
  • HIV-1 / isolation & purification
  • HIV-1 / metabolism
  • Human Immunodeficiency Virus Proteins / genetics*
  • Human Immunodeficiency Virus Proteins / metabolism
  • Humans
  • Interferon-alpha / therapeutic use*
  • Phenotype
  • Viral Regulatory and Accessory Proteins / genetics*
  • Viral Regulatory and Accessory Proteins / metabolism

Substances

  • Antigens, CD
  • BST2 protein, human
  • CD4 Antigens
  • GPI-Linked Proteins
  • Human Immunodeficiency Virus Proteins
  • Interferon-alpha
  • Viral Regulatory and Accessory Proteins
  • vpu protein, Human immunodeficiency virus 1