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- Title
M-Sec induced by HTLV-1 mediates an efficient viral transmission.
- Authors
Hiyoshi, Masateru; Takahashi, Naofumi; Eltalkhawy, Youssef M.; Noyori, Osamu; Lotfi, Sameh; Panaampon, Jutatip; Okada, Seiji; Tanaka, Yuetsu; Ueno, Takaharu; Fujisawa, Jun-ichi; Sato, Yuko; Suzuki, Tadaki; Hasegawa, Hideki; Tokunaga, Masahito; Satou, Yorifumi; Yasunaga, Jun-ichirou; Matsuoka, Masao; Utsunomiya, Atae; Suzu, Shinya
- 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. Author summary: In the present study, we identified the cellular protein M-Sec as a host factor necessary for de novo infection of human T-cell leukemia virus type 1 (HTLV-1), the causative retrovirus of an aggressive blood cancer known as adult T-cell leukemia/lymphoma. The inhibition or knockdown of M-Sec in infected cells resulted in a reduced viral infection in several culture models and a mouse model. We recently demonstrated a similar role of M-Sec in macrophages infected with another human retrovirus HIV-1, but it has been generally thought that M-Sec is not related to HTLV-1 infection because of the lack of its expression in CD4+ T cells, the major target of HTLV-1. In this study, we revealed that CD4+ T cells of HTLV-1 asymptomatic carriers, but not those of HTLV-1- individuals, expressed M-Sec, and that the viral protein Tax mediated the induction of M-Sec. Thus, M-Sec is a new and useful tool for further understanding the process of HTLV-1 transmission.
- Subjects
HTLV-I; VIRAL transmission; VIRAL proteins; LABORATORY mice; CYTOSKELETAL proteins
- Publication
PLoS Pathogens, 2021, Vol 17, Issue 11, p1
- ISSN
1553-7366
- Publication type
Article
- DOI
10.1371/journal.ppat.1010126