Enhanced T cell engraftment after retroviral delivery of an antiviral gene in HIV-infected individuals

Udaykumar Ranga, Clive Woffendin, Sunita Verma, Ling Xu, Carl H. June, D. Keith Bishop, Gary J. Nabel

Research output: Contribution to journalArticle

Abstract

Intracellular expression of gene products that inhibit viral replication -have the potential to complement current antiviral approaches to the treatment of AIDS. We previously have shown that a mutant inhibitory form of an essential viral protein, Rev M10, prolongs the survival of T cells transduced with a nonviral vector in HIV-infected individuals. Because these gene-modified cells were not observed in patients beyond 8 weeks, efforts were made to improve the duration of engraftment. In this study, we used retroviral vector delivery of Rev M10 to CD4+ cells and analyzed relevant immune responses in a pilot study of three HIV-seropositive patients. DNA and RNA PCR analyses revealed that cells transduced with Rev M10 retroviral vectors survived and expressed the recombinant gene for significantly longer time periods than those transduced with a negative control vector in all three patients. Immune responses were not detected either to Rev M10 or to Moloney murine leukemia virus gp70 envelope protein. Rev M10-transduced cells were detected for an average of 6 months after retroviral gene transfer compared with ~3 weeks for the previously reported nonviral vector delivery. These findings suggest that retroviral delivery of an antiviral gene may potentially contribute to immune reconstitution in AIDS and could provide a more effective vector to prolong survival of CD4+ cells in HIV infection.

Original languageEnglish (US)
Pages (from-to)1201-1206
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume95
Issue number3
DOIs
StatePublished - Feb 3 1998
Externally publishedYes

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Antiviral Agents
HIV
T-Lymphocytes
Viral Proteins
Genes
Acquired Immunodeficiency Syndrome
Viral Envelope Proteins
Moloney murine leukemia virus
HIV Infections
Cell Survival
RNA
Polymerase Chain Reaction
DNA
Therapeutics

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Enhanced T cell engraftment after retroviral delivery of an antiviral gene in HIV-infected individuals. / Ranga, Udaykumar; Woffendin, Clive; Verma, Sunita; Xu, Ling; June, Carl H.; Bishop, D. Keith; Nabel, Gary J.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 95, No. 3, 03.02.1998, p. 1201-1206.

Research output: Contribution to journalArticle

Ranga, Udaykumar ; Woffendin, Clive ; Verma, Sunita ; Xu, Ling ; June, Carl H. ; Bishop, D. Keith ; Nabel, Gary J. / Enhanced T cell engraftment after retroviral delivery of an antiviral gene in HIV-infected individuals. In: Proceedings of the National Academy of Sciences of the United States of America. 1998 ; Vol. 95, No. 3. pp. 1201-1206.
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