Genetic variation of herpesvirus saimiri subgroup A transforming protein and its association with cellular src

Heuiran Lee, John J. Trimble, Duk Won Yoon, Dean Regier, Ronald C. Desrosiers, Jae U. Jung

Research output: Contribution to journalArticle

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Abstract

Herpesvirus saimiri strain 11 of subgroup A contains a gene called the saimiri transformation-associated protein, STP, which is not required for viral replication but is required for in vitro immortalization and for the lymphoma-inducing capacity of the virus. To assess the effects of sequence variation on STP function, STP genes from six subgroup A isolates were cloned and sequenced. Sequence comparisons revealed extensive amino acid substitutions within the central region, but the acidic amino terminus and the hydrophobic carboxyl terminus were well conserved. Amino acid identities varied from 73 to 99% among all two-way comparisons. The highly conserved YAEV/I motif at amino acid residues 115 to 118 was preceded by negatively charged glutamic acid residues and thus matched very well the consensus sequence for binding to SH2 domains of src family kinases. The STPs of these subgroup A strains were shown to associate with cellular src and to be an in vitro substrate for src kinase. Mutational analysis of STP-A11 showed that binding to src kinase required the tyrosine residue at 115, showing that YAEV/I is a likely binding motif for src. Also, tyrosine phosphorylation of STP-A11 by src led to subsequent binding to lck and fyn in vitro. Thus, the association of STP with src is likely to be important for T-cell transformation by subgroup A strains of herpesvirus saimiri.

Original languageEnglish (US)
Pages (from-to)3817-3825
Number of pages9
JournalJournal of virology
Volume71
Issue number5
StatePublished - May 1997
Externally publishedYes

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ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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