Potential role of the formation of tunneling nanotubes in HIV-1 spread in macrophages

Michihiro Hashimoto, Farzana Bhuyan, Masateru Hiyoshi, Osamu Noyori, Hesham Nasser, Mitsue Miyazaki, Tamio Saito, Yasumitsu Kondoh, Hiroyuki Osada, Shunsuke Kimura, Koji Hase, Hiroshi Ohno, Shinya Suzu

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42 Citations (Scopus)

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-Sec2 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.

Original languageEnglish
Pages (from-to)1832-1841
Number of pages10
JournalJournal of Immunology
Volume196
Issue number4
DOIs
Publication statusPublished - 2016 Feb 15

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Hashimoto, M., Bhuyan, F., Hiyoshi, M., Noyori, O., Nasser, H., Miyazaki, M., Saito, T., Kondoh, Y., Osada, H., Kimura, S., Hase, K., Ohno, H., & Suzu, S. (2016). Potential role of the formation of tunneling nanotubes in HIV-1 spread in macrophages. Journal of Immunology, 196(4), 1832-1841. https://doi.org/10.4049/jimmunol.1500845