Journal article

Herpes simplex virus pathogenesis in transgenic mice is altered by the homeodomain protein Hox 1.3.

Mitchell W, De Santo R, Zhang S, Odenwald W, Arnheiter H ...see all

Journal of virology, vol. 67, issue 8 (1993) pp. 4484-91

  • 3

    Readers

    Mendeley users who have this article in their library.
  • 12

    Citations

    Citations of this article.
Sign in to save reference

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.

Author-supplied keywords

  • Animals
  • Base Sequence
  • Brain
  • Brain: microbiology
  • Crosses, Genetic
  • DNA-Binding Proteins
  • DNA-Binding Proteins: biosynthesis
  • DNA-Binding Proteins: genetics
  • DNA-Binding Proteins: metabolism
  • Female
  • Gene Expression
  • Globins
  • Globins: biosynthesis
  • Globins: genetics
  • Herpes Simplex
  • Herpes Simplex: etiology
  • Herpes Simplex: genetics
  • Herpes Simplex: pathology
  • Homeodomain Proteins
  • In Situ Hybridization
  • Male
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Mice, Transgenic: microbiology
  • Molecular Sequence Data
  • Oligodeoxyribonucleotides
  • Phosphoproteins
  • Phosphoproteins: biosynthesis
  • Phosphoproteins: genetics
  • Phosphoproteins: metabolism
  • Promoter Regions, Genetic
  • Regulatory Sequences, Nucleic Acid
  • Simplexvirus
  • Simplexvirus: genetics
  • Simplexvirus: pathogenicity
  • Simplexvirus: physiology
  • Virus Replication
  • Virus Replication: genetics

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document

  • PMID: 8392593
  • ISSN: 0022-538X
  • PUI: 23955777
  • SGR: 0027209684
  • SCOPUS: 2-s2.0-0027209684

Authors

  • W J Mitchell

  • R J De Santo

  • S D Zhang

  • W F Odenwald

  • H Arnheiter

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free