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Perturbation of the P-body component Mov10 inhibits HIV-1 infectivity

Vyacheslav Furtak1, Alok Mulky, Stephen A Rawlings

  • 1Department of Microbiology, New York University School of Medicine, New York, New York, United States of America.

Plos One
|February 9, 2010
PubMed

Insights

Mov10 protein inhibits infectious retrovirus production, including HIV. This cellular factor, linked to P-bodies, is crucial for viral particle generation and may involve cytoplasmic RNA processing.

Area of Science:

  • Virology
  • Molecular Biology
  • Cell Biology

Background:

  • Exogenous retroviruses rely on host factors for replication.
  • Host restriction factors that impede retroviral infections are increasingly identified.
  • Mov10, a P-body-associated protein with an RNA helicase domain, is investigated for its role in retroviral replication.

Purpose of the Study:

  • To investigate the role of Mov10 in the production of infectious retroviruses, including HIV.
  • To determine the impact of Mov10 overexpression and knockdown on retroviral infectivity.
  • To elucidate the mechanism by which Mov10 inhibits retroviral production.

Main Methods:

  • Overexpression of Mov10 in cultured cells.
  • siRNA-mediated knockdown of endogenous Mov10.
  • Assessing the infectivity of retroviruses produced in cells with altered Mov10 levels.
  • Analyzing the effect of Mov10 on different retroviral families (lentiviruses, gammaretroviruses).
  • Mapping the functional domains of Mov10 required for HIV inhibition.

Main Results:

  • Overexpression of Mov10 significantly inhibits the production of infectious retroviruses, including HIV, other lentiviruses, and murine leukemia virus.
  • siRNA-mediated reduction of Mov10 modestly suppresses HIV infectivity.
  • HIV produced in the presence of high Mov10 levels is restricted at the pre-reverse transcription stage in target cells.
  • The N-terminal half of Mov10 is essential for its HIV inhibitory activity, while the C-terminal RNA helicase domain is less critical.

Conclusions:

  • Mov10 acts as a restriction factor that interferes with the generation of infectious retroviral particles.
  • The findings suggest Mov10 is required during the lentiviral lifecycle.
  • Mov10's role in P-bodies implicates cytoplasmic RNA processing machinery in controlling infectious retroviral production.

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