Cleavage of human cytomegalovirus protease pUL80a at internal and cryptic sites is not essential but enhances infectivity

Amy N. Loveland, Chee Kai Chan, Edward J. Brignole, Wade Gibson

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

The cytomegalovirus (CMV) maturational protease, assemblin, contains an "internal" (I) cleavage site absent from its homologs in other herpesviruses. Blocking this site for cleavage did not prevent replication of the resulting I- mutant virus. However, cells infected with the I- virus showed increased amounts of a fragment produced by cleavage at the nearby "cryptic" (C) site, suggesting that its replication may bypass the I-site block by using the C site as an alternate cleavage pathway. To test this and further examine the biological importance of these cleavages, we constructed two additional virus mutants-one blocked for C-site cleavage and another blocked for both I- and C-site cleavage. Infectivity comparisons with the parental wild-type virus showed that the I- mutant was the least affected for virus production, whereas infectivity of the C- mutant was reduced by ≈40% and when both sites were blocked virus infectivity was reduced by nearly 90%, providing the first evidence that these cleavages have biological significance. We also present and discuss evidence suggesting that I-site cleavage destabilizes assemblin and its fragments, whereas C-site cleavage does not.

Original languageEnglish
Pages (from-to)12961-12968
Number of pages8
JournalJournal of Virology
Volume79
Issue number20
DOIs
Publication statusPublished - Oct 2005
Externally publishedYes

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Human herpesvirus 5
proteinases
pathogenicity
Viruses
viruses
mutants
Cytomegalovirus
Herpesviridae
assemblin
Peptide Hydrolases

ASJC Scopus subject areas

  • Immunology

Cite this

Cleavage of human cytomegalovirus protease pUL80a at internal and cryptic sites is not essential but enhances infectivity. / Loveland, Amy N.; Chan, Chee Kai; Brignole, Edward J.; Gibson, Wade.

In: Journal of Virology, Vol. 79, No. 20, 10.2005, p. 12961-12968.

Research output: Contribution to journalArticle

Loveland, Amy N. ; Chan, Chee Kai ; Brignole, Edward J. ; Gibson, Wade. / Cleavage of human cytomegalovirus protease pUL80a at internal and cryptic sites is not essential but enhances infectivity. In: Journal of Virology. 2005 ; Vol. 79, No. 20. pp. 12961-12968.
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