Differential function and expression of the viral inhibitor of caspase 8-induced apoptosis (vICA) and the viral mitochondria-localized inhibitor of apoptosis (vMIA) cell death suppressors conserved in primate and rodent cytomegaloviruses

A. Louise McCormick, Anna Skaletskaya, Peter A Barry, Edward S. Mocarski, Victor S. Goldmacher

Research output: Contribution to journalArticle

93 Citations (Scopus)

Abstract

Human cytomegalovirus (CMV) genes UL36 and UL37 encode viral inhibitor of caspase-8-induced apoptosis (vICA) and viral mitochondria inhibitor of apoptosis (vMIA), respectively. Rhesus macaque CMV homologues, denoted Rh-vICA and Rh-vMIA, were identified and found to suppress apoptosis. One of these functions was conserved in MCMV, encoded by the M36 gene and denoted M-vICA. Conserved regions were compared to domains important to vICA- and vMIA-mediated cell death suppression. The conserved sequences of primate CMV vMIA homologues overlapped with the two known functional domains, providing further evidence supporting a crucial role of vMIA in cell death suppression. RNA blot analyses revealed that expression of murine and rhesus macaque CMV UL36 and UL37 homologues started early and continued through late times of infection. Murine CMV homologues were expressed with α (immediate early) kinetics, like human CMV UL36 and UL37, whereas rhesus macaque CMV homologues exhibited β (delayed early) kinetics. Despite differences in organization and transcriptional regulation, this region appears to carry out a conserved role in cell death suppression. When viewed in light of sequence conservation, a functional vMIA homologue appears to be encoded by every primate CMV, whereas a functional vICA homologue appears to be encoded by all cytomegaloviruses for which sequence data are available.

Original languageEnglish (US)
Pages (from-to)221-233
Number of pages13
JournalVirology
Volume316
Issue number2
DOIs
StatePublished - Nov 25 2003

Fingerprint

Caspase 8
Cytomegalovirus
Primates
Rodentia
Mitochondria
Cell Death
Apoptosis
Macaca mulatta
Muromegalovirus
Conserved Sequence
Genes
RNA

Keywords

  • Apoptosis
  • Betaherpesvirus
  • Cell death suppressor
  • Cytomegalovirus
  • UL36
  • UL37
  • vICA
  • vMIA

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases

Cite this

Differential function and expression of the viral inhibitor of caspase 8-induced apoptosis (vICA) and the viral mitochondria-localized inhibitor of apoptosis (vMIA) cell death suppressors conserved in primate and rodent cytomegaloviruses. / McCormick, A. Louise; Skaletskaya, Anna; Barry, Peter A; Mocarski, Edward S.; Goldmacher, Victor S.

In: Virology, Vol. 316, No. 2, 25.11.2003, p. 221-233.

Research output: Contribution to journalArticle

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