Repression of the chromatintethering domain of murine leukemia virus p12

Jonathon D. Brzezinski, Apexa Modi, Mengdan Liu, Monica J. Roth

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Murine leukemia virus (MLV) p12, encoded within Gag, binds the viral preintegration complex (PIC) to the mitotic chromatin. This acts to anchor the viral PIC in the nucleus as the nuclear envelope re-forms postmitosis. Mutations within the p12 C terminus (p12 PM13 to PM15) block early stages in viral replication. Within the p12 PM13 region (p12 60PSPMA65), our studies indicated that chromatin tethering was not detected when the wild-type (WT) p12 protein (M63) was expressed as a green fluorescent protein (GFP) fusion; however, constructs bearing p12-I63 were tethered. N-terminal truncations of the activated p12- I63-GFP indicated that tethering increased further upon deletion of p12 25DLLTEDPPPY34, which includes the late domain required for viral assembly. The p12 PM15 sequence (p12 70RREPP74) is critical for wild-type viral viability; however, virions bearing the PM15 mutation (p12 70AAAAA74) with a second M63I mutant were viable, with a titer 18-fold lower than that of the WT. The p12 M63I mutation amplified chromatin tethering and compensated for the loss of chromatin binding of p12 PM15. Rescue of the p12-M63-PM15 nonviable mutant with prototype foamy virus (PFV) and Kaposi's sarcoma herpesvirus (KSHV) tethering sequences confirmed the function of p1270-74 in chromatin binding. Minimally, full-strength tethering was seen with only p12 61SPIASRLRGRR71 fused to GFP. These results indicate that the p12 C terminus alone is sufficient for chromatin binding and that the presence of the p12 25DLLTEDPPPY34 motif in the N terminus suppresses the ability to tether.

Original languageEnglish (US)
Pages (from-to)11197-11207
Number of pages11
JournalJournal of virology
Volume90
Issue number24
DOIs
StatePublished - 2016

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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