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

Retrovirology. 2020 Jul 10;17(1):20. doi: 10.1186/s12977-020-00528-y.


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.

Keywords: Cell motility; HIV-1; M-sec; Tunneling nanotubes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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


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