Myxoma virus induces extensive CD4 downregulation and dissociation of p56lck in infected rabbit CD4+ T lymphocytes

Michele Barry, Siow Fong Lee, Lynn Boshkov, Grant Mcfadden

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Myxoma virus is a pathogenic poxvirus that induces extensive dysregulation of cellular immunity in infected European rabbits. Infection of a rabbit CD4+ T-cell line (RL-5) with myxoma virus results in dramatic reductions of cell surface levels of CD4 as monitored by flow cytometry. The virus-induced downregulation of CD4 requires early but not late viral gene expression and could not be inhibited by staurosporine, an inhibitor of protein kinase C, which effectively blocks phorbol 12-myristate-13-acetate-induced downregulation of CD4. The decrease in total cellular levels of CD4 during myxoma virus infection could be inhibited by the lysosomotrophic agent NH4Cl, suggesting a lysosomal fate for CD4 during myxoma virus infection. Steady-state levels of the CD4-associated protein tyrosine kinase p56lck remained unchanged during myxoma virus infection, suggesting that p56lck dissociates from CD4 prior to CD4 degradation in virus infected cells. Total p56lck kinase activity was unaffected during myxoma virus infection, although the amount of p56lck physically associated with CD4 declined in parallel with the loss of CD4. Thus, myxoma virus infection of CD4+ T lymphocytes triggers CD4 downregulation via a protein kinase C-independent pathway, causing the dissociation of p56lck and the degradation of CD4 in lysosomal vesicles.

Original languageEnglish (US)
Pages (from-to)5243-5251
Number of pages9
JournalJournal of Virology
Volume69
Issue number9
StatePublished - Sep 1995

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Myxoma virus
Down-Regulation
T-lymphocytes
Virus Diseases
rabbits
Rabbits
T-Lymphocytes
infection
protein kinase C
Protein Kinase C
Poxviridae
Viruses
viruses
protein-tyrosine kinases
Staurosporine
degradation
Viral Genes
Cellular Immunity
cell-mediated immunity
Protein-Tyrosine Kinases

ASJC Scopus subject areas

  • Immunology

Cite this

Myxoma virus induces extensive CD4 downregulation and dissociation of p56lck in infected rabbit CD4+ T lymphocytes. / Barry, Michele; Lee, Siow Fong; Boshkov, Lynn; Mcfadden, Grant.

In: Journal of Virology, Vol. 69, No. 9, 09.1995, p. 5243-5251.

Research output: Contribution to journalArticle

Barry, Michele ; Lee, Siow Fong ; Boshkov, Lynn ; Mcfadden, Grant. / Myxoma virus induces extensive CD4 downregulation and dissociation of p56lck in infected rabbit CD4+ T lymphocytes. In: Journal of Virology. 1995 ; Vol. 69, No. 9. pp. 5243-5251.
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