title: Potential Role of the Formation of Tunneling Nanotubes in HIV-1 Spread in Macrophages.
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.
authors.affiliation: Center for AIDS Research, International Research Center for Medical Sciences, Kumamoto University, Kumamoto, Kumamoto 860-0811, Japan;
authors.forename: Michihiro
authors.initials: M
authors.lastname: Hashimoto
authors.affiliation: Center for AIDS Research, International Research Center for Medical Sciences, Kumamoto University, Kumamoto, Kumamoto 860-0811, Japan;
authors.forename: Farzana
authors.initials: F
authors.lastname: Bhuyan
authors.affiliation: Center for AIDS Research, International Research Center for Medical Sciences, Kumamoto University, Kumamoto, Kumamoto 860-0811, Japan;
authors.forename: Masateru
authors.initials: M
authors.lastname: Hiyoshi
authors.affiliation: Center for AIDS Research, International Research Center for Medical Sciences, Kumamoto University, Kumamoto, Kumamoto 860-0811, Japan;
authors.forename: Osamu
authors.initials: O
authors.lastname: Noyori
authors.affiliation: Center for AIDS Research, International Research Center for Medical Sciences, Kumamoto University, Kumamoto, Kumamoto 860-0811, Japan;
authors.forename: Hesham
authors.initials: H
authors.lastname: Nasser
authors.affiliation: Center for AIDS Research, International Research Center for Medical Sciences, Kumamoto University, Kumamoto, Kumamoto 860-0811, Japan;
authors.forename: Mitsue
authors.initials: M
authors.lastname: Miyazaki
authors.affiliation: RIKEN Center for Sustainable Resource Science, Wako, Saitama 351-0198, Japan; and.
authors.forename: Tamio
authors.initials: T
authors.lastname: Saito
authors.affiliation: RIKEN Center for Sustainable Resource Science, Wako, Saitama 351-0198, Japan; and.
authors.forename: Yasumitsu
authors.identifier: http://orcid.org/0000-0002-3481-5481
authors.initials: Y
authors.lastname: Kondoh
authors.affiliation: RIKEN Center for Sustainable Resource Science, Wako, Saitama 351-0198, Japan; and.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Osada
authors.affiliation: Laboratory for Intestinal Ecosystem, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045, Japan.
authors.forename: Shunsuke
authors.identifier: http://orcid.org/0000-0001-9408-2884
authors.initials: S
authors.lastname: Kimura
authors.affiliation: Laboratory for Intestinal Ecosystem, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Hase
authors.affiliation: Laboratory for Intestinal Ecosystem, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045, Japan.
authors.forename: Hiroshi
authors.identifier: http://orcid.org/0000-0001-8776-9661
authors.initials: H
authors.lastname: Ohno
authors.affiliation: Center for AIDS Research, International Research Center for Medical Sciences, Kumamoto University, Kumamoto, Kumamoto 860-0811, Japan; ssuzu06@kumamoto-u.ac.jp.
authors.forename: Shinya
authors.initials: S
authors.lastname: Suzu
mesh_terms: D015153:Blotting, Western; D002450:Cell Communication / Q000502:physiology*; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D015497:HIV-1 / Q000378:metabolism* / Q000472:pathogenicity*; D006801:Humans; D008264:Macrophages / Q000821:virology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000378:metabolism*
chemical_list: D016207:Cytokines; C085839:TNFAIP2 protein, human; D054311:nef Gene Products, Human Immunodeficiency Virus; C514837:nef protein, Human immunodeficiency virus 1