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Updated: Oct 11, 2025
Dissecting Host-virus Interaction in Lytic Replication of a Model Herpesvirus
Published on: October 7, 2011
M-Sec induced by HTLV-1 mediates an efficient viral transmission
Masateru Hiyoshi1, Naofumi Takahashi2, Youssef M Eltalkhawy2
1Department of Safety Research on Blood and Biological Products, National Institute of Infectious Diseases, Tokyo, Japan.
Abstract:
Human T-cell leukemia virus type 1 (HTLV-1) infects target cells primarily through cell-to-cell routes. Here, we provide evidence that cellular protein M-Sec plays a critical role in this process. When purified and briefly cultured, CD4+ T cells of HTLV-1 carriers, but not of HTLV-1- individuals, expressed M-Sec. The viral protein Tax was revealed to mediate M-Sec induction. Knockdown or pharmacological inhibition of M-Sec reduced viral infection in multiple co-culture conditions. Furthermore, M-Sec knockdown reduced the number of proviral copies in the tissues of a mouse model of HTLV-1 infection. Phenotypically, M-Sec knockdown or inhibition reduced not only plasma membrane protrusions and migratory activity of cells, but also large clusters of Gag, a viral structural protein required for the formation of viral particles. Taken together, these results suggest that M-Sec induced by Tax mediates an efficient cell-to-cell viral infection, which is likely due to enhanced membrane protrusions, cell migration, and the clustering of Gag.
Insights
Cellular protein M-Sec, induced by the Human T-cell leukemia virus type 1 (HTLV-1) Tax protein, is crucial for efficient viral infection. Inhibiting M-Sec reduces HTLV-1 spread and proviral load.
Area of Science:
- Virology
- Cell Biology
- Immunology
Background:
- Human T-cell leukemia virus type 1 (HTLV-1) establishes persistent infections, primarily through cell-to-cell transmission.
- Understanding the molecular mechanisms of HTLV-1 cell-to-cell spread is critical for developing effective antiviral strategies.
Purpose of the Study:
- To investigate the role of cellular protein M-Sec in HTLV-1 infection.
- To elucidate the mechanism by which M-Sec facilitates viral transmission.
Main Methods:
- Analysis of M-Sec expression in CD4+ T cells from HTLV-1 carriers and healthy individuals.
- Investigating the effect of the viral Tax protein on M-Sec induction.
- Utilizing M-Sec knockdown and pharmacological inhibition in co-culture models and a mouse model of HTLV-1 infection.
- Assessing viral infection, proviral load, cell migration, membrane protrusions, and Gag clustering.
Main Results:
- M-Sec is expressed in CD4+ T cells of HTLV-1 carriers and induced by the viral Tax protein.
- M-Sec knockdown or inhibition significantly reduced HTLV-1 infection in vitro and decreased proviral copies in vivo.
- M-Sec manipulation affected cell membrane protrusions, migration, and Gag protein clustering.
Conclusions:
- M-Sec plays a critical role in mediating efficient HTLV-1 cell-to-cell transmission.
- Tax-induced M-Sec enhances viral spread by promoting membrane protrusions, cell migration, and Gag clustering.
