Cell and viral regulatory elements enhance the expression and function of a human immunodeficiency virus inhibitory gene

Udaykumar Ranga, Clive Woffendin, Zhi Yong Yang, X. U. Ling, Sunita Verma, Dan R. Littman, Gary J. Nabel

Research output: Contribution to journalArticle

Abstract

Regulated expression of recombinant genes in CD4+ cells is an important objective for gene therapy of AIDS, as these cells represent the principal target for viral replication of human immunodeficiency virus (HIV). We report here that specific combinations of CD4 cell-specific and viral regulatory elements can enhance expression of an antiviral gene product. Different viral regulatory elements were incorporated into a previously reported CD4 locus control region to increase the expression of reporter genes in T and monocytic cell lines. The CD4-specific regulatory elements were included to enhance expression in CD4 cells, and viral regulatory regions, including the cytomegalovirus immediate-early (CMV IE) upstream enhancer, which contains the KB and Apl regulatory elements and a Tat-responsive element of the HIV type 1 long terminal repeat, were used to increase gene expression and modulate its activity in response to viral infection. In transient transfection assays, this vector was 100- to 1,000-fold more active than the original CD4 regulatory elements alone. Expression of an inhibitory form of the Rev protein, Rev M10, was more effective than previously described vectors and protected against productive viral replication in CD4+ peripheral blood mononuclear cells. The combination of CD4 lineage-specific and viral regulatory elements will facilitate the development of more effective antiviral genetic strategies for AIDS.

Original languageEnglish (US)
Pages (from-to)7020-7029
Number of pages10
JournalJournal of Virology
Volume71
Issue number9
StatePublished - 1997
Externally publishedYes

Fingerprint

Human immunodeficiency virus
HIV
virus replication
Gene Expression
Genes
Antiviral Agents
Acquired Immunodeficiency Syndrome
genes
rev Gene Products
Locus Control Region
HIV Long Terminal Repeat
cells
Cytomegalovirus
terminal repeat sequences
gene therapy
Nucleic Acid Regulatory Sequences
Virus Diseases
transfection
mononuclear leukocytes
Human immunodeficiency virus 1

ASJC Scopus subject areas

  • Immunology

Cite this

Ranga, U., Woffendin, C., Yang, Z. Y., Ling, X. U., Verma, S., Littman, D. R., & Nabel, G. J. (1997). Cell and viral regulatory elements enhance the expression and function of a human immunodeficiency virus inhibitory gene. Journal of Virology, 71(9), 7020-7029.

Cell and viral regulatory elements enhance the expression and function of a human immunodeficiency virus inhibitory gene. / Ranga, Udaykumar; Woffendin, Clive; Yang, Zhi Yong; Ling, X. U.; Verma, Sunita; Littman, Dan R.; Nabel, Gary J.

In: Journal of Virology, Vol. 71, No. 9, 1997, p. 7020-7029.

Research output: Contribution to journalArticle

Ranga, U, Woffendin, C, Yang, ZY, Ling, XU, Verma, S, Littman, DR & Nabel, GJ 1997, 'Cell and viral regulatory elements enhance the expression and function of a human immunodeficiency virus inhibitory gene', Journal of Virology, vol. 71, no. 9, pp. 7020-7029.
Ranga, Udaykumar ; Woffendin, Clive ; Yang, Zhi Yong ; Ling, X. U. ; Verma, Sunita ; Littman, Dan R. ; Nabel, Gary J. / Cell and viral regulatory elements enhance the expression and function of a human immunodeficiency virus inhibitory gene. In: Journal of Virology. 1997 ; Vol. 71, No. 9. pp. 7020-7029.
@article{aa2c58e5bb5d45789b054e4e72018799,
title = "Cell and viral regulatory elements enhance the expression and function of a human immunodeficiency virus inhibitory gene",
abstract = "Regulated expression of recombinant genes in CD4+ cells is an important objective for gene therapy of AIDS, as these cells represent the principal target for viral replication of human immunodeficiency virus (HIV). We report here that specific combinations of CD4 cell-specific and viral regulatory elements can enhance expression of an antiviral gene product. Different viral regulatory elements were incorporated into a previously reported CD4 locus control region to increase the expression of reporter genes in T and monocytic cell lines. The CD4-specific regulatory elements were included to enhance expression in CD4 cells, and viral regulatory regions, including the cytomegalovirus immediate-early (CMV IE) upstream enhancer, which contains the KB and Apl regulatory elements and a Tat-responsive element of the HIV type 1 long terminal repeat, were used to increase gene expression and modulate its activity in response to viral infection. In transient transfection assays, this vector was 100- to 1,000-fold more active than the original CD4 regulatory elements alone. Expression of an inhibitory form of the Rev protein, Rev M10, was more effective than previously described vectors and protected against productive viral replication in CD4+ peripheral blood mononuclear cells. The combination of CD4 lineage-specific and viral regulatory elements will facilitate the development of more effective antiviral genetic strategies for AIDS.",
author = "Udaykumar Ranga and Clive Woffendin and Yang, {Zhi Yong} and Ling, {X. U.} and Sunita Verma and Littman, {Dan R.} and Nabel, {Gary J.}",
year = "1997",
language = "English (US)",
volume = "71",
pages = "7020--7029",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "9",

}

TY - JOUR

T1 - Cell and viral regulatory elements enhance the expression and function of a human immunodeficiency virus inhibitory gene

AU - Ranga, Udaykumar

AU - Woffendin, Clive

AU - Yang, Zhi Yong

AU - Ling, X. U.

AU - Verma, Sunita

AU - Littman, Dan R.

AU - Nabel, Gary J.

PY - 1997

Y1 - 1997

N2 - Regulated expression of recombinant genes in CD4+ cells is an important objective for gene therapy of AIDS, as these cells represent the principal target for viral replication of human immunodeficiency virus (HIV). We report here that specific combinations of CD4 cell-specific and viral regulatory elements can enhance expression of an antiviral gene product. Different viral regulatory elements were incorporated into a previously reported CD4 locus control region to increase the expression of reporter genes in T and monocytic cell lines. The CD4-specific regulatory elements were included to enhance expression in CD4 cells, and viral regulatory regions, including the cytomegalovirus immediate-early (CMV IE) upstream enhancer, which contains the KB and Apl regulatory elements and a Tat-responsive element of the HIV type 1 long terminal repeat, were used to increase gene expression and modulate its activity in response to viral infection. In transient transfection assays, this vector was 100- to 1,000-fold more active than the original CD4 regulatory elements alone. Expression of an inhibitory form of the Rev protein, Rev M10, was more effective than previously described vectors and protected against productive viral replication in CD4+ peripheral blood mononuclear cells. The combination of CD4 lineage-specific and viral regulatory elements will facilitate the development of more effective antiviral genetic strategies for AIDS.

AB - Regulated expression of recombinant genes in CD4+ cells is an important objective for gene therapy of AIDS, as these cells represent the principal target for viral replication of human immunodeficiency virus (HIV). We report here that specific combinations of CD4 cell-specific and viral regulatory elements can enhance expression of an antiviral gene product. Different viral regulatory elements were incorporated into a previously reported CD4 locus control region to increase the expression of reporter genes in T and monocytic cell lines. The CD4-specific regulatory elements were included to enhance expression in CD4 cells, and viral regulatory regions, including the cytomegalovirus immediate-early (CMV IE) upstream enhancer, which contains the KB and Apl regulatory elements and a Tat-responsive element of the HIV type 1 long terminal repeat, were used to increase gene expression and modulate its activity in response to viral infection. In transient transfection assays, this vector was 100- to 1,000-fold more active than the original CD4 regulatory elements alone. Expression of an inhibitory form of the Rev protein, Rev M10, was more effective than previously described vectors and protected against productive viral replication in CD4+ peripheral blood mononuclear cells. The combination of CD4 lineage-specific and viral regulatory elements will facilitate the development of more effective antiviral genetic strategies for AIDS.

UR - http://www.scopus.com/inward/record.url?scp=0030860481&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030860481&partnerID=8YFLogxK

M3 - Article

VL - 71

SP - 7020

EP - 7029

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 9

ER -