Extracellular nef protein activates signal transduction pathway from ras to mitogen-activated protein kinase cascades that leads to activation of human immunodeficiency virus from latency

Minoru Tobiume, Koh Fujinaga, Satoko Suzuki, Satoshi Komoto, Tetsu Mukai, Kazuyoshi Ikuta

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

We previously reported that viral antigen expression was markedly up-regulated by stimulation with extra-cellular Nef, similar to the effects of tumor necrosis factor (TNF)-α and phorbol myristate acetate, in model cells for HIV-1 latency. In this study, we examined the molecular mechanism of this novel Nef function. Flow cytometry revealed specific binding of Nef on the surface of latently infected cells. Furthermore, activation of Ras in the cells was detected after treatment with Nef, indicating the involvement of Ras in Nef-mediated activation of HIV-1 from latency. This was also confirmed by the observations that HIV-1 long-terminal repeat-luciferase (LTR-Luc) activity was significantly up-regulated by introduction of the active Ras into uninfected cells, and that LTR-Luc activity observed in Nef-treated cells was specifically inhibited by introduction of a dominant negative Ras. In addition, PD98059 inhibited the activation of HIV-1 by Nef, but not by TNF-α. Thus, Nef-mediated reactivation of HIV-1 in latent model cells occurs by signal transduction from Ras to mitogen-activated protein kinase cascades.

Original languageEnglish
Pages (from-to)461-467
Number of pages7
JournalAIDS Research and Human Retroviruses
Volume18
Issue number6
DOIs
Publication statusPublished - 01-01-2002

Fingerprint

nef Gene Products
Virus Latency
Mitogen-Activated Protein Kinases
Signal Transduction
HIV-1
HIV
Luciferases
Tumor Necrosis Factor-alpha
HIV Long Terminal Repeat
Terminal Repeat Sequences
Viral Antigens
Tetradecanoylphorbol Acetate
Flow Cytometry

All Science Journal Classification (ASJC) codes

  • Immunology
  • Virology
  • Infectious Diseases

Cite this

@article{ddd3cb000f9a460da0f7a8c5bd76371b,
title = "Extracellular nef protein activates signal transduction pathway from ras to mitogen-activated protein kinase cascades that leads to activation of human immunodeficiency virus from latency",
abstract = "We previously reported that viral antigen expression was markedly up-regulated by stimulation with extra-cellular Nef, similar to the effects of tumor necrosis factor (TNF)-α and phorbol myristate acetate, in model cells for HIV-1 latency. In this study, we examined the molecular mechanism of this novel Nef function. Flow cytometry revealed specific binding of Nef on the surface of latently infected cells. Furthermore, activation of Ras in the cells was detected after treatment with Nef, indicating the involvement of Ras in Nef-mediated activation of HIV-1 from latency. This was also confirmed by the observations that HIV-1 long-terminal repeat-luciferase (LTR-Luc) activity was significantly up-regulated by introduction of the active Ras into uninfected cells, and that LTR-Luc activity observed in Nef-treated cells was specifically inhibited by introduction of a dominant negative Ras. In addition, PD98059 inhibited the activation of HIV-1 by Nef, but not by TNF-α. Thus, Nef-mediated reactivation of HIV-1 in latent model cells occurs by signal transduction from Ras to mitogen-activated protein kinase cascades.",
author = "Minoru Tobiume and Koh Fujinaga and Satoko Suzuki and Satoshi Komoto and Tetsu Mukai and Kazuyoshi Ikuta",
year = "2002",
month = "1",
day = "1",
doi = "10.1089/088922202753614227",
language = "English",
volume = "18",
pages = "461--467",
journal = "AIDS Research and Human Retroviruses",
issn = "0889-2229",
publisher = "Mary Ann Liebert Inc.",
number = "6",

}

Extracellular nef protein activates signal transduction pathway from ras to mitogen-activated protein kinase cascades that leads to activation of human immunodeficiency virus from latency. / Tobiume, Minoru; Fujinaga, Koh; Suzuki, Satoko; Komoto, Satoshi; Mukai, Tetsu; Ikuta, Kazuyoshi.

In: AIDS Research and Human Retroviruses, Vol. 18, No. 6, 01.01.2002, p. 461-467.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Extracellular nef protein activates signal transduction pathway from ras to mitogen-activated protein kinase cascades that leads to activation of human immunodeficiency virus from latency

AU - Tobiume, Minoru

AU - Fujinaga, Koh

AU - Suzuki, Satoko

AU - Komoto, Satoshi

AU - Mukai, Tetsu

AU - Ikuta, Kazuyoshi

PY - 2002/1/1

Y1 - 2002/1/1

N2 - We previously reported that viral antigen expression was markedly up-regulated by stimulation with extra-cellular Nef, similar to the effects of tumor necrosis factor (TNF)-α and phorbol myristate acetate, in model cells for HIV-1 latency. In this study, we examined the molecular mechanism of this novel Nef function. Flow cytometry revealed specific binding of Nef on the surface of latently infected cells. Furthermore, activation of Ras in the cells was detected after treatment with Nef, indicating the involvement of Ras in Nef-mediated activation of HIV-1 from latency. This was also confirmed by the observations that HIV-1 long-terminal repeat-luciferase (LTR-Luc) activity was significantly up-regulated by introduction of the active Ras into uninfected cells, and that LTR-Luc activity observed in Nef-treated cells was specifically inhibited by introduction of a dominant negative Ras. In addition, PD98059 inhibited the activation of HIV-1 by Nef, but not by TNF-α. Thus, Nef-mediated reactivation of HIV-1 in latent model cells occurs by signal transduction from Ras to mitogen-activated protein kinase cascades.

AB - We previously reported that viral antigen expression was markedly up-regulated by stimulation with extra-cellular Nef, similar to the effects of tumor necrosis factor (TNF)-α and phorbol myristate acetate, in model cells for HIV-1 latency. In this study, we examined the molecular mechanism of this novel Nef function. Flow cytometry revealed specific binding of Nef on the surface of latently infected cells. Furthermore, activation of Ras in the cells was detected after treatment with Nef, indicating the involvement of Ras in Nef-mediated activation of HIV-1 from latency. This was also confirmed by the observations that HIV-1 long-terminal repeat-luciferase (LTR-Luc) activity was significantly up-regulated by introduction of the active Ras into uninfected cells, and that LTR-Luc activity observed in Nef-treated cells was specifically inhibited by introduction of a dominant negative Ras. In addition, PD98059 inhibited the activation of HIV-1 by Nef, but not by TNF-α. Thus, Nef-mediated reactivation of HIV-1 in latent model cells occurs by signal transduction from Ras to mitogen-activated protein kinase cascades.

UR - http://www.scopus.com/inward/record.url?scp=0036247913&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036247913&partnerID=8YFLogxK

U2 - 10.1089/088922202753614227

DO - 10.1089/088922202753614227

M3 - Article

C2 - 11958689

AN - SCOPUS:0036247913

VL - 18

SP - 461

EP - 467

JO - AIDS Research and Human Retroviruses

JF - AIDS Research and Human Retroviruses

SN - 0889-2229

IS - 6

ER -