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M-Sec promotes the production of infectious HIV-1 virus through the exocyst complex

Reem M Mahmoud1,2, Masateru Hiyoshi3, Randa A Abdelnaser1

  • 1Division of Infection & Hematopoiesis, Joint Research Center for Human Retrovirus Infection, Kumamoto University, Kumamoto, Japan.

Biorxiv : the Preprint Server for Biology
|November 26, 2025
PubMed

Insights

The cellular protein M-Sec enhances human immunodeficiency virus type 1 (HIV-1) production and transmission. M-Sec regulates viral Gag protein puncta formation and Env incorporation, crucial for infectious virus release.

Area of Science:

  • Virology
  • Cell Biology
  • Molecular Biology

Background:

  • The cellular protein M-Sec is known to promote human immunodeficiency virus type 1 (HIV-1) transmission.
  • The precise molecular mechanisms underlying M-Sec's role in HIV-1 transmission remain incompletely elucidated.

Purpose of the Study:

  • To investigate the role of M-Sec in the production of infectious HIV-1.
  • To elucidate the molecular mechanisms by which M-Sec enhances HIV-1 transmission.

Main Methods:

  • Knockdown and overexpression of M-Sec in infected cells.
  • Analysis of Gag puncta formation and Gag/Env co-localization.
  • Quantification of viral Env incorporation and infectivity.
  • Investigation of M-Sec interactions with PIP2, Ral, and the exocyst complex.

Main Results:

  • M-Sec knockdown impaired Gag puncta formation, Gag/Env co-localization, Env incorporation, and viral infectivity.
  • M-Sec overexpression enhanced Gag puncta formation, Gag/Env co-localization, Env incorporation, and viral infectivity.
  • M-Sec's regulation of HIV-1 requires phosphatidylinositol 4,5-bisphosphate (PIP2), Ral, and the exocyst complex.

Conclusions:

  • M-Sec significantly promotes the production of infectious HIV-1 particles.
  • M-Sec influences HIV-1 transmission by modulating viral structural protein organization and incorporation.
  • M-Sec utilizes PIP2, Ral, and the exocyst complex to regulate both cellular structures and viral production, thereby enhancing HIV-1 transmission.

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