title: HIV-1 infection ex vivo accelerates measles virus infection by upregulating signaling lymphocytic activation molecule (SLAM) in CD4+ T cells.
abstract: Measles virus (MV) infection in children harboring human immunodeficiency virus type 1 (HIV-1) is often fatal, even in the presence of neutralizing antibodies; however, the underlying mechanisms are unclear. Therefore, the aim of the present study was to examine the interaction between HIV-1 and wild-type MV (MVwt) or an MV vaccine strain (MVvac) during dual infection. The results showed that the frequencies of MVwt- and MVvac-infected CD4(+) T cells within the resting peripheral blood mononuclear cells (PBMCs) were increased 3- to 4-fold after HIV-1 infection, and this was associated with a marked upregulation of signaling lymphocytic activation molecule (SLAM) expression on CD4(+) T cells but not on CD8(+) T cells. SLAM upregulation was induced by infection with a replication-competent HIV-1 isolate comprising both the X4 and R5 types and to a lesser extent by a pseudotyped HIV-1 infection. Notably, SLAM upregulation was observed in HIV-infected as well as -uninfected CD4(+) T cells and was abrogated by the removal of HLA-DR(+) cells from the PBMC culture. Furthermore, SLAM upregulation did not occur in uninfected PBMCs cultured together with HIV-infected PBMCs in compartments separated by a permeable membrane, indicating that no soluble factors were involved. Rather, CD4(+) T cell activation mediated through direct contact with dendritic cells via leukocyte function-associated molecule 1 (LFA-1)/intercellular adhesion molecule 1 (ICAM-1) and LFA-3/CD2 was critical. Thus, HIV-1 infection induces a high level of SLAM expression on CD4(+) T cells, which may enhance their susceptibility to MV and exacerbate measles in coinfected individuals.
authors.affiliation: Department of Immunology, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo, Japan.
authors.forename: Yu-ya
authors.initials: YY
authors.lastname: Mitsuki
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Terahara
authors.forename: Kentaro
authors.initials: K
authors.lastname: Shibusawa
authors.forename: Takuya
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Takatsugu
authors.initials: T
authors.lastname: Tsuchiya
authors.forename: Fuminori
authors.initials: F
authors.lastname: Mizukoshi
authors.forename: Masayuki
authors.initials: M
authors.lastname: Ishige
authors.forename: Seiji
authors.initials: S
authors.lastname: Okada
authors.forename: Kazuo
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Yuko
authors.initials: Y
authors.lastname: Morikawa
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Nakayama
authors.forename: Makoto
authors.initials: M
authors.lastname: Takeda
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Yanagi
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Tsunetsugu-Yokota
mesh_terms: D015703:Antigens, CD / Q000096:biosynthesis*; D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D002478:Cells, Cultured; D015497:HIV-1 / Q000472:pathogenicity*; D006801:Humans; D008459:Measles virus / Q000472:pathogenicity*; D011956:Receptors, Cell Surface / Q000096:biosynthesis*; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D015854:Up-Regulation
chemical_list: D015703:Antigens, CD; D011956:Receptors, Cell Surface; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1