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 wha...
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doaj-512bd970c5174ee5914755ae544d006f2020-11-25T03:52:13ZengBMCRetrovirology1742-46902020-07-0117111110.1186/s12977-020-00528-yM-Sec facilitates intercellular transmission of HIV-1 through multiple mechanismsSameh Lotfi0Hesham Nasser1Osamu Noyori2Masateru Hiyoshi3Hiroaki Takeuchi4Yoshio Koyanagi5Shinya Suzu6Division of Infection & Hematopoiesis, Joint Research Center for Human Retrovirus Infection, Kumamoto UniversityDivision of Infection & Hematopoiesis, Joint Research Center for Human Retrovirus Infection, Kumamoto UniversityDivision of Infection & Hematopoiesis, Joint Research Center for Human Retrovirus Infection, Kumamoto UniversityDepartment of Safety Research On Blood and Biological Products, National Institute of Infectious DiseasesDepartment of Molecular Virology, Tokyo Medical and Dental UniversityLaboratory of Systems Virology, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto UniversityDivision of Infection & Hematopoiesis, Joint Research Center for Human Retrovirus Infection, Kumamoto UniversityAbstract 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.http://link.springer.com/article/10.1186/s12977-020-00528-yHIV-1M-secTunneling nanotubesCell motility |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Sameh Lotfi Hesham Nasser Osamu Noyori Masateru Hiyoshi Hiroaki Takeuchi Yoshio Koyanagi Shinya Suzu |
spellingShingle |
Sameh Lotfi Hesham Nasser Osamu Noyori Masateru Hiyoshi Hiroaki Takeuchi Yoshio Koyanagi Shinya Suzu M-Sec facilitates intercellular transmission of HIV-1 through multiple mechanisms Retrovirology HIV-1 M-sec Tunneling nanotubes Cell motility |
author_facet |
Sameh Lotfi Hesham Nasser Osamu Noyori Masateru Hiyoshi Hiroaki Takeuchi Yoshio Koyanagi Shinya Suzu |
author_sort |
Sameh Lotfi |
title |
M-Sec facilitates intercellular transmission of HIV-1 through multiple mechanisms |
title_short |
M-Sec facilitates intercellular transmission of HIV-1 through multiple mechanisms |
title_full |
M-Sec facilitates intercellular transmission of HIV-1 through multiple mechanisms |
title_fullStr |
M-Sec facilitates intercellular transmission of HIV-1 through multiple mechanisms |
title_full_unstemmed |
M-Sec facilitates intercellular transmission of HIV-1 through multiple mechanisms |
title_sort |
m-sec facilitates intercellular transmission of hiv-1 through multiple mechanisms |
publisher |
BMC |
series |
Retrovirology |
issn |
1742-4690 |
publishDate |
2020-07-01 |
description |
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. |
topic |
HIV-1 M-sec Tunneling nanotubes Cell motility |
url |
http://link.springer.com/article/10.1186/s12977-020-00528-y |
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