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Gamma-interferon-inducible, lysosome/endosome-localized thiolreductase, GILT, has anti-retroviral activity and its expression is counteracted by HIV-1.
Kubo, Yoshinao; Izumida, Mai; Yashima, Yuka; Yoshii-Kamiyama, Haruka; Tanaka, Yuetsu; Yasui, Kiyoshi; Hayashi, Hideki; Matsuyama, Toshifumi.
Afiliação
  • Kubo Y; Division of Cytokine Signaling, Graduate School of Medical Sciences, Nagasaki University, Nagasaki, Japan.
  • Izumida M; Department of AIDS Research, Institute of Tropical Medicine, G-COE, Nagasaki University, Nagasaki, Japan.
  • Yashima Y; Division of Cytokine Signaling, Graduate School of Medical Sciences, Nagasaki University, Nagasaki, Japan.
  • Yoshii-Kamiyama H; Division of Cytokine Signaling, Graduate School of Medical Sciences, Nagasaki University, Nagasaki, Japan.
  • Tanaka Y; Division of Cytokine Signaling, Graduate School of Medical Sciences, Nagasaki University, Nagasaki, Japan.
  • Yasui K; Department of AIDS Research, Institute of Tropical Medicine, G-COE, Nagasaki University, Nagasaki, Japan.
  • Hayashi H; Department of Immunology, Graduate School and Faculty of Medicine, University of the Ryukyus, Okinawa, Japan.
  • Matsuyama T; Division of Cytokine Signaling, Graduate School of Medical Sciences, Nagasaki University, Nagasaki, Japan.
Oncotarget ; 7(44): 71255-71273, 2016 Nov 01.
Article em En | MEDLINE | ID: mdl-27655726
ABSTRACT
The mechanism by which type II interferon (IFN) inhibits virus replications remains to be identified. Murine leukemia virus (MLV) replication was significantly restricted by γ-IFN, but not human immunodeficiency virus type 1 (HIV-1) replication. Because MLV enters host cells via endosomes, we speculated that certain cellular factors among γ-IFN-induced, endosome-localized proteins inhibit MLV replication. We found that γ-IFN-inducible lysosomal thiolreductase (GILT) significantly restricts HIV-1 replication as well as MLV replication by its thiolreductase activity. GILT silencing enhanced replication-defective HIV-1 vector infection and virion production in γ-IFN-treated cells, although γ-IFN did not inhibit HIV-1 replication. This result showed that GILT is required for the anti-viral activity of γ-IFN. Interestingly, GILT protein level was increased by γ-IFN in uninfected cells and env-deleted HIV-1-infected cells, but not in full-length HIV-1-infected cells. γ-IFN-induced transcription from the γ-IFN-activation sequence was attenuated by the HIV-1 Env protein. These results suggested that the γ-IFN cannot restrict HIV-1 replication due to the inhibition of γ-IFN signaling by HIV-1 Env. Finally, we found that 4,4'-dithiodipyridine (4-PDS), which inhibits S-S bond formation at acidic pH, significantly suppresses HIV-1 vector infection and virion production, like GILT. In conclusion, this study showed that GILT functions as a host restriction factor against the retroviruses, and a GILT mimic, 4-PDS, is the leading compound for the development of novel concept of anti-viral agents.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: HIV-1 / Antirretrovirais / Oxirredutases atuantes sobre Doadores de Grupo Enxofre Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: Oncotarget Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Japão

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: HIV-1 / Antirretrovirais / Oxirredutases atuantes sobre Doadores de Grupo Enxofre Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: Oncotarget Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Japão