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J Immunol. 2016 Feb 15;196(4):1832-41. doi: 10.4049/jimmunol.1500845. Epub 2016 Jan 15.

Potential Role of the Formation of Tunneling Nanotubes in HIV-1 Spread in Macrophages.

Author information

1
Center for AIDS Research, International Research Center for Medical Sciences, Kumamoto University, Kumamoto, Kumamoto 860-0811, Japan;
2
RIKEN Center for Sustainable Resource Science, Wako, Saitama 351-0198, Japan; and.
3
Laboratory for Intestinal Ecosystem, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045, Japan.
4
Center for AIDS Research, International Research Center for Medical Sciences, Kumamoto University, Kumamoto, Kumamoto 860-0811, Japan; ssuzu06@kumamoto-u.ac.jp.

Abstract

Tunneling nanotubes (TNTs), the long membrane extensions connecting distant cells, have emerged as a novel form of cell-to-cell communication. However, it is not fully understood how and to what extent TNTs contribute to intercellular spread of pathogens including HIV-1. In this study, we show that HIV-1 promotes TNT formation per se via its protein Nef and a cellular protein M-Sec, which appears to mediate approximately half of viral spread among monocyte-derived macrophages (MDMs). A small compound that inhibits M-Sec-induced TNT formation reduced HIV-1 production by almost half in MDMs. Such inhibition was not observed with Nef-deficient mutant HIV-1 that fails to promote TNT formation and replicates less efficiently than the wild-type HIV-1 in MDMs. The TNT inhibitor-sensitive/Nef-promoting viral production was also observed in a T cell line ectopically expressing M-Sec, but not in another M-Sec(-) T cell line. Our results suggest the importance of TNTs in HIV-1 spread among MDMs and might answer the long-standing question how Nef promotes HIV-1 production in a cell type-specific manner.

PMID:
26773158
DOI:
10.4049/jimmunol.1500845
[Indexed for MEDLINE]
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