CMPK2 and BCL-G are associated with type 1 interferon-induced HIV restriction in humans

Sci Adv. 2018 Aug 1;4(8):eaat0843. doi: 10.1126/sciadv.aat0843. eCollection 2018 Aug.

Abstract

Type 1 interferons (IFN) are critical for host control of HIV and simian immunodeficiency virus. However, it is unknown which of the hundreds of interferon-stimulated genes (ISGs) restrict HIV in vivo. We sequenced RNA from cells that support HIV replication (activated CD4+ T cells) in 19 HIV-infected people before and after interferon-α2b (IFN-α2b) injection. IFN-α2b administration reduced plasma HIV RNA and induced mRNA expression in activated CD4+ T cells: The IFN-α2b-induced change of each mRNA was compared to the change in plasma HIV RNA. Of 99 ISGs, 13 were associated in magnitude with plasma HIV RNA decline. In addition to well-known restriction factors among the 13 ISGs, two novel genes, CMPK2 and BCL-G, were identified and confirmed for their ability to restrict HIV in vitro: The effect of IFN on HIV restriction in culture was attenuated with RNA interference to CMPK2, and overexpression of BCL-G diminished HIV replication. These studies reveal novel antiviral molecules that are linked with IFN-mediated restriction of HIV in humans.

Publication types

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

MeSH terms

  • Antiviral Agents / pharmacology
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology*
  • Gene Expression Regulation
  • HIV / drug effects*
  • HIV Infections / drug therapy*
  • HIV Infections / immunology
  • HIV Infections / metabolism
  • Humans
  • Interferon Regulatory Factors / genetics
  • Interferon Regulatory Factors / metabolism*
  • Interferon-alpha / pharmacology*
  • Prospective Studies
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Virus Replication / drug effects*

Substances

  • Antiviral Agents
  • BCL2L14 protein, human
  • Interferon Regulatory Factors
  • Interferon-alpha
  • Interferon-alpha2b
  • Proto-Oncogene Proteins c-bcl-2