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M-Sec facilitates intercellular transmission of HIV-1 through multiple mechanisms

M-Sec facilitates intercellular transmission of HIV-1 through multiple mechanisms

Authors :
Osamu Noyori
Masateru Hiyoshi
Sameh Lotfi
Hiroaki Takeuchi
Yoshio Koyanagi
Hesham Nasser
Shinya Suzu
Source :
Retrovirology, Retrovirology, Vol 17, Iss 1, Pp 1-11 (2020)
Publication Year :
2020
Publisher :
Springer Science and Business Media LLC, 2020.

Abstract

Background HIV-1 promotes the formation of tunneling nanotubes (TNTs) that connect distant cells, aiding cell-to-cell viral transmission between macrophages. Our recent study suggests that the cellular protein M-Sec plays a role in these processes. However, the timing, mechanism, and to what extent M-Sec contributes to HIV-1 transmission is not fully understood, and the lack of a cell line model that mimics macrophages has hindered in-depth analysis. Results We found that HIV-1 increased the number, length and thickness of TNTs in a manner dependent on its pathogenic protein Nef and M-Sec in U87 cells, as observed in macrophages. In addition, we found that M-Sec was required not only for TNT formation but also motility of U87 cells, both of which are beneficial for viral transmission. In fact, M-Sec knockdown in U87 cells led to a significantly delayed viral production in both cellular and extracellular fractions. This inhibition was observed for wild-type virus, but not for a mutant virus lacking Nef, which is known to promote not only TNT formation but also migration of infected macrophages. Conclusions By taking advantage of useful features of U87 cells, we provided evidence that M-Sec mediates a rapid and efficient cell–cell transmission of HIV-1 at an early phase of infection by enhancing both TNT formation and cell motility.

Details

ISSN :
17424690
Volume :
17
Database :
OpenAIRE
Journal :
Retrovirology
Accession number :
edsair.doi.dedup.....468fec2a7fd0b7705c4efaade361467f
Full Text :
https://doi.org/10.1186/s12977-020-00528-y