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Cell biology of HIV-1 Nef and Vpr

Research Project

Project/Area Number 10470078
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Virology
Research InstitutionThe University of Tokushima

Principal Investigator

ADACHI Akio  Univ. Tokushima Sch. Med, Professor, 医学部, 教授 (90127043)

Co-Investigator(Kenkyū-buntansha) AKARI Hirofumi  Univ. Tokushima Sch. Med, Assistant Professor, 医学部, 助手 (20294671)
KOYAMA Hajime  Univ. Tokushima Sch. Med, Associate Professor, 医学部, 助教授 (80109074)
Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥13,000,000 (Direct Cost: ¥13,000,000)
Fiscal Year 1999: ¥4,300,000 (Direct Cost: ¥4,300,000)
Fiscal Year 1998: ¥8,700,000 (Direct Cost: ¥8,700,000)
KeywordsHIV / Nef / Vpr / MHC-I / CD4 / Apoptosis
Research Abstract

In this study, we have demonstrated the detaild action mechanisms of HIV-1 Nef and the strong apoptosis-inducing ability of HIV-1 Vpr.
HIV-1 Nef has been reported to act via modulation of viral particles to enhance virus infectivity. We showed that HIV-1 virions produced in the absence of Nef are defective for the processes of virus entry and DNA synthesis. Requirement of HIV-1 Nef for efficient entry of HIV-l into cells was producer cell-dependent The PxxP and RR domains were both dispensable for enhanced viral entry, thus suggesting that another interaction of Nef with a cellular factor(s) is involved in the process of viral entry. It has been reported that various important functions such as the viral infectivity, incorporation of Nef into virions, and down-regulation of MHC-I are mapped to the N-terminal portion of HIV-1 Nef. We showed, by the analysis of point mutants regarding 20th amino acid of the Nef, that Nef-induced MHC-I down-regulation is functionally dissociated from its virion incorporation, enhancement of viral infectivity, and CD4 down-regulation.
It is controversial about the regulation of apoptosis by Vpr. Some report that Vpr induces apoptosis, and others that Vpr shows anti-apoptotic function. To determine whether HIV-1 Vpr is an inducer of apoptosis, we analyzed the cells infected with HIV-1/VSV pseudotype virus. This system does not require the selection of cells producing Vpr, and thus it is possible to directly monitor the apoptosis in cells. We showed by this system that HIV- 1 Vpr is a strong inducer of apoptosis, and that Vpr displays no detectable anti-apoptotic action.
In conclusion, we have made great progress in understanding the biology of HIV-1 Nef and Vpr. It is much clearer that the detaild studies on the functions in vivo of HIV-1 Nef and Vpr is required.

Report

(3 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • Research Products

    (24 results)

All Other

All Publications (24 results)

  • [Publications] Fukumori,T.: "The HTV-1 Vpr displays,strong anti-apoptotic activity"FEBS Letters. 432. 17-20 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tokunaga,K.: "Enhancement of human immunodeficiency virus type 1 infectivity by Nef is producer....."Journal of General Virology. 79. 2447-2453 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tokunaga,K.: "Producer cell-dependent requirement of the Nef protein for efficient entry of....."Biochemical and Biophysical Research Communications. 250. 565-568 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tokunaga,K.: "The cellular kinase binding motifs(PxxP and RR)in human immunodeficiency virus...."Virology. 257. 285-289 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Akari,H.: "Pseudotyping HIV-1 by vesicular stomatitis virus G protein does not reduce the....."Journal of General Virology. 80. 2945-2949 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Akari,H.: "Nef-induced major I histocompatibility complex class I down-regulation is functionally...."Journal of Virology. (in press). (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Fukumori, T., et al.: "The HIV-1 Vpr displays strong anti-apoptotic activity."FEBS Letters. 432. 17-20 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tokunaga, K., et al.: "Enhancement of human immunodeficiency virus type 1 infectivity by Nef is producer cell-dependent."Journal of General Virology. 79. 2447-2453 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tokunaga, K., et al.: "Producer cell-dependent requirement of the Nef protein for efficient entry of HIV-1 into cells."Biochemical and Biophysical Research Communications. 250. 565-568 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tokunaga, K., et al.: "The cellular kinase binding motifs (PxxP and RR) in human immunodeficiency virus type 1 Nef protein are dispensable for producer cell-dependent enhancement of viral entry."Virology. 257. 285-289 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Akari, H., et al.: "Pseudotyping HIV-1 by vesicular stomatitis virus G protein does not reduce the cell-dependent requirement of Vif for optimal infectivity: functional difference between Vif and Nef."Journal of General Virology. 80. 2945-2949 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Akari, H., et al.: "Nef-induced major histocompatibiity complex class I down-regulation is functionally dissociated from its virion incorporation, enhancement of viral infectivity, and CD4 down-regulation."Journal of Virology. (in press). (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Akari,H.: "Cell-dependent requirement of human immunodeficiency virus type 1 gp41 ・・・・."Journal of Virology. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Akari,H.: "Nef-induced major histocompatibility complex class I down-regulation is ・・・・."Journal of Virology. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Akari,H.: "Pseudotyping HIV-1 by vesicular stomatitis virus G protein does not reduce the ・・・・."Journal of General Virology. 80. 2945-2949 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Akari,H.: "Effects of SIVmac infection on peripheral blood CD4_+ CD8_+ T lymphocytes in ・・・・."Clinical Immunology. 91. 321-329 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Tokunaga,K.: "The cellular kinase binding motifs (PxxP and RR) in human immunodeficiency virus・・・・."Virology. 257. 285-289 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Adachi,A.: "Cell-dependent functional roles of HIV-1 Nef for viral replication."International Journal of Molecular Medicine. 3. 427-430 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Inubushi,R.: "The potential of various HIV-1 mutants to inhibit the repli-cation of wild-type virus." Biochemical and Biophysical Research Communications. 247. 349-352 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Shimano,R.: "Suppression of HIV-2 replication by HIV-1 gag mutants." Biochemical and Biophysical Research Communications. 248. 418-421 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kawamura,M.: "Early function of HIV-1 Gag proteins is cell-dependent." Biochemical and Biophysical Research Communications. 248. 899-903 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Fukumori,T.: "The HIV-1 Vpr displays strong anti-apoptotic activity." FEBS Letters. 432. 17-20 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Tokunaga,K.: "Enhancement of human immunodeficiency virus type 1 infectivity by Nef is producer cell-dependent." Journal of General Virology. 79. 2447-2453 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Tokunaga,K.: "Producer cell-dependent requirement of the Nef protein for efficient entry of HIV-1 into cells." Biochemical and Biophysical Research Communications. 250. 565-568 (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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