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Updated: Jun 3, 2026

Phagosome Migration and Velocity Measured in Live Primary Human Macrophages Infected with HIV-1
Published on: September 5, 2016
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.
Abstract:
We have demonstrated that the cellular protein M-Sec promotes the transmission of human immunodeficiency virus type 1 (HIV-1) in macrophages. However, the underlying mechanism is not fully understood. Here, we report that M-Sec promotes the production of infectious HIV-1 virus. The major viral structural protein Gag distributed as many puncta in infected cells, which is one of the indicators of viral particle formation. The knockdown of M-Sec hindered the Gag puncta formation and co-localization of Gag with the viral envelope protein Env in cells, and reduced the amount of Env and infectivity of the produced virus. Consistent with these results, the over-expression of M-Sec induced the accumulation of Gag puncta, Gag/Env co-localization, and Env incorporation into virus and viral infectivity. M-Sec is known to bind phosphatidylinositol 4,5-bisphosphate (PIP2) and a small GTPase Ral, both of which were required for the M-Sec-mediated HIV-1 regulation. The exocyst complex, which is the downstream effector of Ral, was also required for the M-Sec-mediated HIV-1 regulation. Because PIP2, Ral and the exocyst complex are important for the M-Sec-mediated formation of the long plasma membrane protrusions, the present study suggests that M-Sec promotes HIV-1 transmission by acting on both cell structures and viral production through these overlapping components.
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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