APOBEC3G/3A Expression in Human Immunodeficiency Virus Type 1-Infected Individuals Following Initiation of Antiretroviral Therapy Containing Cenicriviroc or Efavirenz

Front Immunol. 2018 Aug 8:9:1839. doi: 10.3389/fimmu.2018.01839. eCollection 2018.

Abstract

Apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3 (APOBEC3) family members are cytidine deaminases that play crucial roles in innate responses to retrovirus infection. The mechanisms by which some of these enzymes restrict human immunodeficiency virus type 1 (HIV-1) replication have been extensively investigated in vitro. However, little is known regarding how APOBEC3 proteins affect the pathogenesis of HIV-1 infection in vivo and how antiretroviral therapy influences their expression. In this work, a longitudinal analysis was performed to evaluate APOBEC3G/3A expression in peripheral blood mononuclear cells of antiretroviral-naive HIV-1-infected individuals treated with cenicriviroc (CVC) or efavirenz (EFV) at baseline and 4, 12, 24, and 48 weeks post-treatment follow-up. While APOBEC3G expression was unaffected by therapy, APOBEC3A levels increased in CVC but not EFV arm at week 48 of treatment. APOBEC3G expression correlated directly with CD4+ cell count and CD4+/CD8+ cell ratio, whereas APOBEC3A levels inversely correlated with plasma soluble CD14. These findings suggest that higher APOBEC3G/3A levels may be associated with protective effects against HIV-1 disease progression and chronic inflammation and warrant further studies.

Keywords: APOBEC3A; APOBEC3G; antiretroviral therapy; cenicriviroc; chronic inflammation; disease progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • APOBEC-3G Deaminase / genetics*
  • APOBEC-3G Deaminase / metabolism
  • Adult
  • Alkynes
  • Anti-HIV Agents / therapeutic use
  • Antiretroviral Therapy, Highly Active
  • Benzoxazines / therapeutic use
  • CD4 Lymphocyte Count
  • Cyclopropanes
  • Cytidine Deaminase / genetics*
  • Cytidine Deaminase / metabolism
  • Disease Progression
  • Female
  • Gene Expression Regulation* / drug effects
  • HIV Infections / drug therapy
  • HIV Infections / genetics*
  • HIV Infections / immunology
  • HIV Infections / virology*
  • HIV-1* / drug effects
  • Humans
  • Imidazoles / therapeutic use
  • Male
  • Middle Aged
  • Proteins / genetics*
  • Proteins / metabolism
  • Sulfoxides
  • Treatment Outcome
  • Viral Load
  • Young Adult

Substances

  • Alkynes
  • Anti-HIV Agents
  • Benzoxazines
  • Cyclopropanes
  • Imidazoles
  • Proteins
  • Sulfoxides
  • cenicriviroc
  • APOBEC-3G Deaminase
  • APOBEC3A protein, human
  • APOBEC3G protein, human
  • Cytidine Deaminase
  • efavirenz