Evidence for a different susceptibility of primate lentiviruses to type I interferons

J Virol. 2013 Mar;87(5):2587-96. doi: 10.1128/JVI.02553-12. Epub 2012 Dec 19.

Abstract

Type I interferons induce a complex transcriptional program that leads to a generalized antiviral response against a large panel of viruses, including human immunodeficiency virus type 1 (HIV-1). However, despite the fact that interferons negatively regulate HIV-1 ex vivo, a chronic interferon state is linked to the progression of AIDS and to robust viral replication, rather than protection, in vivo. To explain this apparent contradiction, we hypothesized that HIV-1 may have evolved a partial resistance to interferon, and to test this hypothesis, we analyzed the effects of alpha interferon (IFN-α) on the infectivity of HIV-1, human immunodeficiency virus type 2 (HIV-2), and rhesus monkey simian immunodeficiency virus (SIVmac). The results we obtained indicate that HIV-1 is more resistant to an IFN-α-induced response than are HIV-2 and SIVmac. Our data indicate that the accumulation of viral DNA is more compromised following the infection of IFN-α-treated cells with HIV-2 and SIVmac than with HIV-1. This defect correlates with a faster destabilization of HIV-2 viral nucleoprotein complexes (VNCs), suggesting a link between VNC destabilization and impaired viral DNA (vDNA) accumulation. The differential susceptibilities to IFN-α of the primate lentiviruses tested here do not map to the capsid protein (CA), excluding de facto a role for human tripartite motif protein isoform 5 alpha (Trim5α) in this restriction; this also suggests that an additional restriction mechanism differentially affects primate lentivirus infection. The different behaviors of HIV-1 and HIV-2 with respect to IFN-α responses may account at least in part for the differences in pathogenesis observed between these two virus types.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Capsid Proteins / drug effects
  • Cell Line, Tumor
  • DNA, Viral / genetics
  • DNA, Viral / metabolism
  • HEK293 Cells
  • HIV Infections / drug therapy
  • HIV Infections / virology
  • HIV-1 / immunology
  • HIV-1 / physiology*
  • HIV-2 / immunology
  • HIV-2 / physiology*
  • HeLa Cells
  • Human Immunodeficiency Virus Proteins / metabolism
  • Humans
  • Interferon-alpha / immunology*
  • Macrophages / virology
  • Membrane Glycoproteins
  • Retroviridae Proteins / metabolism
  • Simian Immunodeficiency Virus / immunology
  • Simian Immunodeficiency Virus / physiology*
  • Viral Envelope Proteins
  • Viral Nonstructural Proteins / metabolism
  • Virus Replication* / drug effects

Substances

  • Capsid Proteins
  • DNA, Viral
  • G protein, vesicular stomatitis virus
  • Human Immunodeficiency Virus Proteins
  • Interferon-alpha
  • Membrane Glycoproteins
  • Retroviridae Proteins
  • Viral Envelope Proteins
  • Viral Nonstructural Proteins