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

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.

• Authors: Sameh Lotfi, Hesham Nasser, Osamu Noyori, Masateru Hiyoshi, Hiroaki Takeuchi, Yoshio Koyanagi, Shinya Suzu
• Journal: Retrovirology (Retrovirology) Vol. 17 Issue 1 Pg. 20 (07 10 2020) ISSN: 1742-4690 [Electronic] England
• PMID: 32650782 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• TNFAIP2 protein, human
• nef Gene Products, Human Immunodeficiency Virus
• nef protein, Human immunodeficiency virus 1

Topics

• Cell Line
• Cell Movement
• Cytokines (genetics, metabolism)
• HIV-1 (genetics, growth & development, physiology)
• Humans
• Intercellular Junctions (metabolism, virology)
• Macrophages (virology)
• Mutation
• nef Gene Products, Human Immunodeficiency Virus (genetics, metabolism)