Increased expression and dysregulated association of restriction factors and type I interferon in HIV, HCV mono- and co-infected patients

J Med Virol. 2016 Jun;88(6):987-95. doi: 10.1002/jmv.24419. Epub 2015 Nov 9.

Abstract

Host restriction factors and type I interferon are important in limiting HIV and HCV infections, yet the role of HIV, HCV mono- and co-infection in regulating these antiviral genes expression is not clear. In this study, we measured the levels of TRIM5α, TRIM22, APOBEC3G, and IFN-α, -β mRNA expression in peripheral blood mononuclear cells of 43 HIV mono-infected, 70 HCV mono-infected and 64 HIV/HCV co-infected patients along with 98 healthy controls. We also quantified HIV and HCV viral loads in mono- and co-infected patients. The results showed that HCV, HIV mono- and co-infection differentially increased TRIM22, APOBEC3G, and IFN-α, -β mRNA expression while the mRNA expression of TRIMα was upregulated only by HCV-mono infection. HIV/HCV co-infection was associated with higher viral load, compared to either HIV or HCV mono-infection. Additionally, we showed TRIMα and TRIM22 positively correlated with IFN-α, -β, which could be dysregulated by HIV, HCV mono- and co-infection. Furthermore, we found TRIM22 negatively correlated with HCV viral load in mono-infected patients and APOBEC3G positively correlated with HCV viral load in co-infected patients. Collectively, our findings suggest the potential role of restriction factors in restricting HIV, HCV mono- and co-infection in vivo, which appears to be a therapeutic target for potential drug discovery.

Keywords: HCV; HIV; co-infection; restriction factors; type I interferon.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • APOBEC-3G Deaminase / genetics
  • Adult
  • Antiviral Restriction Factors
  • Carrier Proteins / genetics
  • Coinfection / blood
  • Coinfection / genetics*
  • Coinfection / virology
  • Cross-Sectional Studies
  • Drug Discovery
  • Female
  • Gene Expression Regulation
  • Genotype
  • HIV / physiology
  • HIV Infections / complications
  • HIV Infections / genetics*
  • HIV Infections / immunology
  • HIV Infections / virology
  • Hepacivirus / physiology
  • Hepatitis C / complications
  • Hepatitis C / genetics*
  • Hepatitis C / immunology
  • Hepatitis C / virology
  • Hepatitis C, Chronic / complications
  • Hepatitis C, Chronic / genetics*
  • Hepatitis C, Chronic / immunology
  • Hepatitis C, Chronic / virology
  • Host-Pathogen Interactions / genetics*
  • Humans
  • Interferon Type I / genetics*
  • Interferon Type I / immunology
  • Interferon-alpha / genetics
  • Leukocytes, Mononuclear / immunology
  • Male
  • Middle Aged
  • Minor Histocompatibility Antigens / genetics
  • Repressor Proteins / genetics
  • Tripartite Motif Proteins / genetics
  • Ubiquitin-Protein Ligases
  • Viral Load

Substances

  • Antiviral Restriction Factors
  • Carrier Proteins
  • IFNA1 protein, human
  • Interferon Type I
  • Interferon-alpha
  • Minor Histocompatibility Antigens
  • Repressor Proteins
  • TRIM22 protein, human
  • Tripartite Motif Proteins
  • TRIM5 protein, human
  • Ubiquitin-Protein Ligases
  • APOBEC-3G Deaminase
  • APOBEC3G protein, human