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The ability of SAMHD1 to block HIV-1 but not SIV requires expression of MxB

Cindy Buffone1, Juliane Kutzner2, Silvana Opp1

  • 1Albert Einstein College of Medicine, Microbiology and Immunology, Bronx, NY, 10461, USA.

Virology
|April 9, 2019
PubMed

Insights

MxB is essential for SAMHD1

Area of Science:

  • Virology
  • Immunology
  • Molecular Biology

Background:

  • SAMHD1 acts as a human restriction factor, inhibiting HIV-1 infection in immune cells.
  • The role of MxB in modulating SAMHD1's antiviral activity against HIV-1 was previously unclear.

Purpose of the Study:

  • To investigate the necessity of MxB for SAMHD1's restriction of HIV-1.
  • To elucidate the mechanism by which MxB enhances SAMHD1's antiviral function.

Main Methods:

  • Generated human THP-1 cell lines with knockout/knockdown of MxB and/or SAMHD1.
  • Assessed HIV-1 and SIVmac infection levels in modified cell lines and primary macrophages.
  • Performed pull-down assays to examine SAMHD1-MxB interactions.
  • Analyzed SAMHD1's subcellular localization, T592 phosphorylation, and dNTP levels.

Main Results:

  • MxB depletion abolished SAMHD1's ability to restrict HIV-1, but not SIVmac.
  • Similar findings were observed in MxB knockdown primary human macrophages.
  • SAMHD1 restriction of HIV-1 was demonstrated to be dependent on MxB expression.

Conclusions:

  • MxB is a critical cofactor for SAMHD1's restriction of HIV-1.
  • The antiviral mechanism of SAMHD1 against HIV-1 relies on the presence of MxB.
Keywords:
HIV-1MxBRestriction factorsSAMHD1SIVmac

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