Use of a human immunodeficiency virus type 1 Rev mutant without nucleolar dysfunction as a candidate for potential AIDS therapy

Rika A. Furuta, Satoshi Kubota, Masatoshi Maki, Yukio Miyazaki, Toshio Hattori, Masakazu Hatanaka

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Applications of transdominant mutants of human immunodeficiency virus type 1 (HIV-1) regulatory proteins, especially Rev mutant, have been attempted for gene therapy against AIDS, because the Rev protein is essential for viral replication. We have previously reported that a mutant Rev protein (dRev) lacking its nucleolar targeting signal remained out of nuclei in expressed cells and strongly inhibited the function of Rev. To investigate the effects of dRev on HIV-1 replication, we established several dRev-expressing human cell lines with two different vector systems and examined virus production in these cells. An HIV-1-derived vector containing drev cDNA was constructed and introduced into CD4-positive HeLa cells and cells of the human T-cell line CCRF-CEM (CEM). In dRev-expressing HeLa cells, virus replication, syncytium formation, and cell death caused by HIV-1 infection were remarkably suppressed, and the same vector also conferred a resistant phenotype on CEM cells. The production was also suppressed in CEM cells containing the drev gene driven by a cytomegalovirus promoter. In addition, we found that dRev did not cause nucleolar dysfunction in a transient assay, in contrast to other transdominant mutants and wild-type Rev. Since dRev cannot migrate into the nuclei, it is expected not to interfere with nuclear/nucleolar functions of the host cell. We conclude that dRev is one promising candidate as an antiviral molecule for gene therapy against AIDS.

Original languageEnglish
Pages (from-to)1591-1599
Number of pages9
JournalJournal of Virology
Volume69
Issue number3
Publication statusPublished - Mar 1995
Externally publishedYes

Fingerprint

Human immunodeficiency virus 1
HIV-1
Acquired Immunodeficiency Syndrome
rev Gene Products
mutants
therapeutics
cells
Virus Replication
HeLa Cells
Genetic Therapy
gene therapy
Therapeutics
virus replication
Cell Line
Virus Diseases
Mutant Proteins
Giant Cells
Cytomegalovirus
Antiviral Agents
human cell lines

ASJC Scopus subject areas

  • Immunology

Cite this

Use of a human immunodeficiency virus type 1 Rev mutant without nucleolar dysfunction as a candidate for potential AIDS therapy. / Furuta, Rika A.; Kubota, Satoshi; Maki, Masatoshi; Miyazaki, Yukio; Hattori, Toshio; Hatanaka, Masakazu.

In: Journal of Virology, Vol. 69, No. 3, 03.1995, p. 1591-1599.

Research output: Contribution to journalArticle

Furuta, Rika A. ; Kubota, Satoshi ; Maki, Masatoshi ; Miyazaki, Yukio ; Hattori, Toshio ; Hatanaka, Masakazu. / Use of a human immunodeficiency virus type 1 Rev mutant without nucleolar dysfunction as a candidate for potential AIDS therapy. In: Journal of Virology. 1995 ; Vol. 69, No. 3. pp. 1591-1599.
@article{16c14398f7574ac7833b2aa7d727fb74,
title = "Use of a human immunodeficiency virus type 1 Rev mutant without nucleolar dysfunction as a candidate for potential AIDS therapy",
abstract = "Applications of transdominant mutants of human immunodeficiency virus type 1 (HIV-1) regulatory proteins, especially Rev mutant, have been attempted for gene therapy against AIDS, because the Rev protein is essential for viral replication. We have previously reported that a mutant Rev protein (dRev) lacking its nucleolar targeting signal remained out of nuclei in expressed cells and strongly inhibited the function of Rev. To investigate the effects of dRev on HIV-1 replication, we established several dRev-expressing human cell lines with two different vector systems and examined virus production in these cells. An HIV-1-derived vector containing drev cDNA was constructed and introduced into CD4-positive HeLa cells and cells of the human T-cell line CCRF-CEM (CEM). In dRev-expressing HeLa cells, virus replication, syncytium formation, and cell death caused by HIV-1 infection were remarkably suppressed, and the same vector also conferred a resistant phenotype on CEM cells. The production was also suppressed in CEM cells containing the drev gene driven by a cytomegalovirus promoter. In addition, we found that dRev did not cause nucleolar dysfunction in a transient assay, in contrast to other transdominant mutants and wild-type Rev. Since dRev cannot migrate into the nuclei, it is expected not to interfere with nuclear/nucleolar functions of the host cell. We conclude that dRev is one promising candidate as an antiviral molecule for gene therapy against AIDS.",
author = "Furuta, {Rika A.} and Satoshi Kubota and Masatoshi Maki and Yukio Miyazaki and Toshio Hattori and Masakazu Hatanaka",
year = "1995",
month = "3",
language = "English",
volume = "69",
pages = "1591--1599",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "3",

}

TY - JOUR

T1 - Use of a human immunodeficiency virus type 1 Rev mutant without nucleolar dysfunction as a candidate for potential AIDS therapy

AU - Furuta, Rika A.

AU - Kubota, Satoshi

AU - Maki, Masatoshi

AU - Miyazaki, Yukio

AU - Hattori, Toshio

AU - Hatanaka, Masakazu

PY - 1995/3

Y1 - 1995/3

N2 - Applications of transdominant mutants of human immunodeficiency virus type 1 (HIV-1) regulatory proteins, especially Rev mutant, have been attempted for gene therapy against AIDS, because the Rev protein is essential for viral replication. We have previously reported that a mutant Rev protein (dRev) lacking its nucleolar targeting signal remained out of nuclei in expressed cells and strongly inhibited the function of Rev. To investigate the effects of dRev on HIV-1 replication, we established several dRev-expressing human cell lines with two different vector systems and examined virus production in these cells. An HIV-1-derived vector containing drev cDNA was constructed and introduced into CD4-positive HeLa cells and cells of the human T-cell line CCRF-CEM (CEM). In dRev-expressing HeLa cells, virus replication, syncytium formation, and cell death caused by HIV-1 infection were remarkably suppressed, and the same vector also conferred a resistant phenotype on CEM cells. The production was also suppressed in CEM cells containing the drev gene driven by a cytomegalovirus promoter. In addition, we found that dRev did not cause nucleolar dysfunction in a transient assay, in contrast to other transdominant mutants and wild-type Rev. Since dRev cannot migrate into the nuclei, it is expected not to interfere with nuclear/nucleolar functions of the host cell. We conclude that dRev is one promising candidate as an antiviral molecule for gene therapy against AIDS.

AB - Applications of transdominant mutants of human immunodeficiency virus type 1 (HIV-1) regulatory proteins, especially Rev mutant, have been attempted for gene therapy against AIDS, because the Rev protein is essential for viral replication. We have previously reported that a mutant Rev protein (dRev) lacking its nucleolar targeting signal remained out of nuclei in expressed cells and strongly inhibited the function of Rev. To investigate the effects of dRev on HIV-1 replication, we established several dRev-expressing human cell lines with two different vector systems and examined virus production in these cells. An HIV-1-derived vector containing drev cDNA was constructed and introduced into CD4-positive HeLa cells and cells of the human T-cell line CCRF-CEM (CEM). In dRev-expressing HeLa cells, virus replication, syncytium formation, and cell death caused by HIV-1 infection were remarkably suppressed, and the same vector also conferred a resistant phenotype on CEM cells. The production was also suppressed in CEM cells containing the drev gene driven by a cytomegalovirus promoter. In addition, we found that dRev did not cause nucleolar dysfunction in a transient assay, in contrast to other transdominant mutants and wild-type Rev. Since dRev cannot migrate into the nuclei, it is expected not to interfere with nuclear/nucleolar functions of the host cell. We conclude that dRev is one promising candidate as an antiviral molecule for gene therapy against AIDS.

UR - http://www.scopus.com/inward/record.url?scp=0028893540&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028893540&partnerID=8YFLogxK

M3 - Article

C2 - 7853493

AN - SCOPUS:0028893540

VL - 69

SP - 1591

EP - 1599

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 3

ER -