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

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

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

Plos Pathogens
|June 1, 2026
PubMed

Insights

The cellular protein M-Sec enhances human immunodeficiency virus type 1 (HIV-1) production and infectivity in macrophages. It regulates viral particle formation and incorporation of viral proteins, aiding HIV-1 transmission.

Area of Science:

  • Virology
  • Cell Biology
  • Immunology

Background:

  • The cellular protein M-Sec is known to promote human immunodeficiency virus type 1 (HIV-1) transmission in macrophages.
  • The precise mechanism by which M-Sec influences HIV-1 production and infectivity remains incompletely understood.

Purpose of the Study:

  • To elucidate the mechanism underlying M-Sec's role in HIV-1 production and transmission.
  • To investigate the impact of M-Sec on viral particle formation, protein incorporation, and infectivity.

Main Methods:

  • Knockdown and overexpression of M-Sec in infected macrophages.
  • Analysis of Gag puncta formation and Gag/Env co-localization.
  • Quantification of viral Env incorporation and infectivity.
  • Investigation of M-Sec's interactions with phosphatidylinositol 4,5-bisphosphate (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 PIP2, Ral, and the exocyst complex, which are also involved in M-Sec-mediated plasma membrane protrusions.

Conclusions:

  • M-Sec significantly promotes infectious HIV-1 production by influencing viral structural protein organization and Env incorporation.
  • M-Sec facilitates HIV-1 transmission by modulating both cellular structures and viral production pathways via PIP2, Ral, and the exocyst complex.

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