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Herpes simplex virus pathogenesis in transgenic mice is altered by the homeodomain protein Hox 1.3.
- Source :
-
Journal of virology [J Virol] 1993 Aug; Vol. 67 (8), pp. 4484-91. - Publication Year :
- 1993
-
Abstract
- The DNA sequence TAAT is the core binding motif for the mouse homeodomain protein Hox 1.3 (proposed new name, Hoxa-5). These sequences are present within the multiple TAATGARAT regulatory motifs in the promoters of the immediate-early genes which control herpes simplex virus type 1 replication. To investigate the role of this homeodomain protein in the regulation of herpes simplex virus gene expression and pathogenesis, transgenic mice containing a mouse Hox 1.3 cDNA under the control of the virus- and interferon-inducible Mx 1 promoter were generated. After infection of transgenic mice with herpes simplex virus, Hox 1.3 RNA and protein were expressed at the sites of virus replication. In these transgenic mice, herpes simplex virus replication, spread of virus through the host, and virus-induced mortality were markedly enhanced. Increased spread and replication of herpes simplex virus were also observed in cultured fibroblasts from transgenic mice. This finding suggests that in vivo, Hox 1.3 may increase viral spread by increasing viral replication at the level of the individual infected cells. These results demonstrate that expression of a transgene encoding a single host protein, Hox 1.3, alters the pathogenesis of experimental herpes simplex virus infection. We conclude that a protein that belongs to a class of DNA-binding proteins which are best known for their role in regulating embryonic development may also regulate herpesvirus pathogenesis.
- Subjects :
- Animals
Base Sequence
Crosses, Genetic
DNA-Binding Proteins biosynthesis
DNA-Binding Proteins metabolism
Female
Gene Expression
Globins biosynthesis
Globins genetics
Herpes Simplex etiology
Herpes Simplex pathology
In Situ Hybridization
Male
Mice
Mice, Inbred C3H
Mice, Inbred C57BL
Molecular Sequence Data
Oligodeoxyribonucleotides
Phosphoproteins biosynthesis
Phosphoproteins metabolism
Promoter Regions, Genetic
Simplexvirus physiology
Transcription Factors
Virus Replication genetics
Brain microbiology
DNA-Binding Proteins genetics
Herpes Simplex genetics
Homeodomain Proteins
Mice, Transgenic microbiology
Phosphoproteins genetics
Regulatory Sequences, Nucleic Acid
Simplexvirus genetics
Simplexvirus pathogenicity
Subjects
Details
- Language :
- English
- ISSN :
- 0022-538X
- Volume :
- 67
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Journal of virology
- Publication Type :
- Academic Journal
- Accession number :
- 8392593
- Full Text :
- https://doi.org/10.1128/JVI.67.8.4484-4491.1993