A PLPPV sequence in the p8 region of Gag provides late domain function for mouse mammary tumor virus

Virology. 2019 Sep:535:272-278. doi: 10.1016/j.virol.2019.07.015. Epub 2019 Jul 19.

Abstract

The late (L) domain sequence used by mouse mammary tumor virus (MMTV) remains undefined. Similar to other L domain-containing proteins, MMTV p8 and p14NC proteins are monoubiquitinated, suggesting L domain function. Site-directed mutagenesis of p8, PLPPV, and p14NC, PLPPL, sequences in MMTV Gag revealed a requirement only for the PLPPV sequence in virion release in a position-dependent manner. Electron microscopy of a defective Gag mutant confirmed an L domain budding defect morphology. The equine infectious anemia virus (EIAV) YPDL core L domain sequence and PLPPV provided L domain function in reciprocal MMTV and EIAV Gag exchange mutants, respectively. Alanine scanning of the PLPPV sequence revealed a strict requirement for the valine residue but only minor requirements for any one of the other residues. Thus, PLPPV provides MMTV L domain function, representing a fourth type of retroviral L domain that enables MMTV Gag proteins to co-opt cellular budding pathways for release.

Keywords: Budding; Gag; Gag assembly; Late domain; MMTV; Mouse mammary tumor virus; Retrovirus.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Motifs*
  • Animals
  • Gene Products, gag / chemistry
  • Gene Products, gag / genetics
  • Gene Products, gag / metabolism*
  • HEK293 Cells
  • Humans
  • Mammary Tumor Virus, Mouse / chemistry
  • Mammary Tumor Virus, Mouse / genetics
  • Mammary Tumor Virus, Mouse / growth & development*
  • Mice
  • Microscopy, Electron
  • Virus Release*

Substances

  • Gene Products, gag