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

研究成果: Article査読

25 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)1591-1599
ページ数9
ジャーナルJournal of virology
69
3
DOI
出版ステータスPublished - 1995 3月
外部発表はい

ASJC Scopus subject areas

  • 微生物学
  • 免疫学
  • 昆虫科学
  • ウイルス学

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