Abstract

We will continue to investigate the structural/functional features of herpes simplex virus type 1 genes important in their controlled expression during productive infection. We will use reporter plasmids capable of being activated by trans-acting viral product because of their convenience in the manipulation of specific sequence elements involved in regulation. Such methods will be used to precisely identify sequence elements in selected viral leaders that are responsive to trans-activation by viral gene products and to examine the role of template replication on the expression of genes of different temporal classes. Sequence elements identified as important in virus-specific activation and repression of transcription will be utilized as probes to investigate the nature of the interaction between viral control sequences and specific regulatory proteins expressed during viral replication. Selected sequences will be modified and reintroduced into the virus itself so that alterations in expression of marker genes during productive infection can be examined. We have characterized a single gene expressed as mRNA during latent infection and will now characterize the anti-ICPO gene in terms of its sequence, control of its expression, and the protein products encoded by it. Such information will be used to manipulate the expression of anti-ICO to investigate the molecular basis for the exclusive expression of this transcript in neurons and any role it may have in productive infection.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37CA011861-23
Application #
3481636
Study Section
Experimental Virology Study Section (EVR)
Project Start
1978-05-01
Project End
1993-04-30
Budget Start
1992-05-01
Budget End
1993-04-30
Support Year
23
Fiscal Year
1992
Total Cost
Indirect Cost

  Institution

Name
University of California Irvine
Department
Type
Schools of Arts and Sciences
DUNS #
161202122
City
Irvine
State
CA
Country
United States
Zip Code
92697

  Publications

Zeier, Zane; Aguilar, J Santiago; Lopez, Cecilia M et al. (2009) A limited innate immune response is induced by a replication-defective herpes simplex virus vector following delivery to the murine central nervous system. J Neurovirol 15:411-24
Aguilar, Jose Santiago; Held, Katherine S; Wagner, Edward K (2007) Herpes simplex virus type 1 shows multiple interactions with sulfonated compounds at binding, penetration, and cell-to-cell passage. Virus Genes 34:241-8
Aguilar, J S; Devi-Rao, G V; Rice, M K et al. (2006) Quantitative comparison of the HSV-1 and HSV-2 transcriptomes using DNA microarray analysis. Virology 348:233-41
Aguilar, J S; Ghazal, Peter; Wagner, Edward K (2005) Design of a herpes simplex virus type 2 long oligonucleotide-based microarray: global analysis of HSV-2 transcript abundance during productive infection. Methods Mol Biol 292:423-48
Karaca, Gamze; Hargett, Danna; McLean, Tim I et al. (2004) Inhibition of the stress-activated kinase, p38, does not affect the virus transcriptional program of herpes simplex virus type 1. Virology 329:142-56
O'Neil, J E; Loutsch, J M; Aguilar, J S et al. (2004) Wide variations in herpes simplex virus type 1 inoculum dose and latency-associated transcript expression phenotype do not alter the establishment of latency in the rabbit eye model. J Virol 78:5038-44
Sun, Aixu; Devi-Rao, G V; Rice, M K et al. (2004) Immediate-early expression of the herpes simplex virus type 1 ICP27 transcript is not critical for efficient replication in vitro or in vivo. J Virol 78:10470-8
Sun, Aixu; Devi-Rao, G V; Rice, M K et al. (2004) The TATGARAT box of the HSV-1 ICP27 gene is essential for immediate early expression but not critical for efficient replication in vitro or in vivo. Virus Genes 29:335-43
Tran, Robert K; Lieu, Pauline T; Aguilar, Santiago et al. (2002) Altering the expression kinetics of VP5 results in altered virulence and pathogenesis of herpes simplex virus type 1 in mice. J Virol 76:2199-205
Yang, William C; Devi-Rao, G V; Ghazal, Peter et al. (2002) General and specific alterations in programming of global viral gene expression during infection by VP16 activation-deficient mutants of herpes simplex virus type 1. J Virol 76:12758-74

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