Herpes simplex virus trans-regulatory protein ICP27 stabilizes and binds to 3' ends of labile mRNA

C. R. Brown, M. S. Nakamura, J. D. Mosca, G. S. Hayward, S. E. Straus, L. P. Perera

Research output: Contribution to journalArticlepeer-review

72 Scopus citations


Previous work demonstrated that a herpes simplex virus type 1 (HSV-1) immediate-early function up-regulates beta interferon but not chloramphenicol acetyltransferase reporter genes driven by the strong simian virus 40 (SV40) or cytomegalovirus promoter-enhancer regions in both transient assays and stable cell lines. The different 3' mRNA stabilization and RNA-processing signals from these two reporter genes appeared to be primarily responsible for this phenomenon. We now report that the HSV-1 ICP27 itself is sufficient to stimulate both steady-state accumulation and increased half-life of beta interferon reporter gene mRNA. Furthermore, the ability to respond directly to cotransfected ICP27 can be transferred to chloramphenicol acetyltransferase reporter genes by replacement of their SV40-derived splicing and poly(A) signals with the 3' AU-rich and poly(A) RNA-processing signals from the normally highly labile beta interferon and c-myc mRNA species. ICP27 expressed in bacteria bound specifically to in vitro- generated RNA from both the beta interferon and c-myc intronless AU-rich 3' RNA-processing regions, but not to the SV40-derived early-region splice signal and poly(A) sequences. By site-specific mutagenesis, we also show that individual ICP27 C-terminal amino acid residues that are positionally conserved in ICP27 homologs in other herpesviruses (D-357, E-358, H-479, C- 400, C-483, and C-488) are critical far trans-regulatory activity. Importantly, several of these positions match mutations that are known to be essential for the role of ICP27 in the early-to-late switch during the virus lytic cycle. Therefore, our findings support the notion that HSV ICP27 modulates gene expression posttranscriptionally in part by targeting RNA.

Original languageEnglish (US)
Pages (from-to)7187-7195
Number of pages9
JournalJournal of virology
Issue number11
StatePublished - 1995
Externally publishedYes

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology


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