Chen, Benjamin K. and Feinberg, Mark B. and Baltimore, David (1997) The kappaB sites in the human immunodeficiency virus type 1 long terminal repeat enhance virus replication yet are not absolutely required for viral growth. Journal of Virology, 71 (7). pp. 5495-5504. ISSN 0022-538X http://resolver.caltech.edu/CaltechAUTHORS:CHEjvir97
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The dependence of human immunodeficiency virus type 1 (HIV-1) on its NF- kappaB binding sites (kappaB sites) for replication in transformed and primary T-cell targets was examined by infecting cells with HIV-1 reporter viruses containing kappaB site enhancer mutations. Viral transcription was measured either with luciferase-expressing HIV-1 that infects for a single round or by flow cytometric analyses with HIV-1 expressing placental alkaline phosphatase (PLAP) or green-fluorescent protein (GFP). Both PLAP- and GFP-expressing viruses spread from cell to cell and allowed analysis of viral gene expression patterns in single cells. Infection of a panel of T-cell lines with different basal levels of NF-kappaB demonstrated a direct correlation between the amount of constitutive nuclear NF-kappaB and the degree to which a wild- type virus outperformed kappaB site mutants. One T-cell line with a constitutively high level of nuclear NF-kappaB, PM1, showed a 20-fold decrease in transcription when its kappaB sites were mutated. In contrast, in a T-cell line with a low basal level of NF-kappaB, SupT1, mutation of the kappaB site in the enhancer had no effect on viral transcription or growth rate. Phytohemagglutinin-activated peripheral blood mononuclear cells showed a large dependence on the kappaB sites for optimal virus growth. Viruses without marker genes corroborated the finding that mutations to the kappaB sites impair virus production in cells with a high basal level of NF-kappaB. These data show that in T cells, HIV-1 can use NF-kappaB to enhance its growth but the virus is clearly able to grow in its absence.
|Additional Information:||Copyright © 1997, American Society for Microbiology Received 21 January 1997/Accepted 16 April 1997 Thanks to Linqi Zhang, Chris Roman, Rajesh Gandhi, George Cohen, Kalle Saksela, and Alex Hoffman for critical comments on the manuscript. We are grateful to Richard Young and the Whitehead Institute for use of their BL-3 facilities. B.K.C. was supported by a Medical Scientist Training Program grant.|
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|Deposited On:||26 Apr 2006|
|Last Modified:||26 Dec 2012 08:50|
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