Late domain-dependent inhibition of equine infectious anemia virus budding

J Virol. 2004 Jan;78(2):724-32. doi: 10.1128/jvi.78.2.724-732.2004.


The Gag proteins of a number of different retroviruses contain late or L domains that promote the release of virions from the plasma membrane. Three types of L domains have been identified to date: Pro-Thr-Ala-Pro (PTAP), Pro-Pro-X-Tyr, and Tyr-Pro-Asp-Leu. It has previously been demonstrated that overexpression of the N-terminal, E2-like domain of the endosomal sorting factor TSG101 (TSG-5') inhibits human immunodeficiency virus type 1 (HIV-1) release but does not affect the release of the PPPY-containing retrovirus murine leukemia virus (MLV), whereas overexpression of the C-terminal portion of TSG101 (TSG-3') potently disrupts both HIV-1 and MLV budding. In addition, it has been reported that, while the release of a number of retroviruses is disrupted by proteasome inhibitors, equine infectious anemia virus (EIAV) budding is not affected by these agents. In this study, we tested the ability of TSG-5', TSG-3', and full-length TSG101 (TSG-F) overexpression, a dominant negative form of the AAA ATPase Vps4, and proteasome inhibitors to disrupt the budding of EIAV particles bearing each of the three types of L domain. The results indicate that (i) inhibition by TSG-5' correlates with dependence on PTAP; (ii) the release of wild-type EIAV (EIAV/WT) is insensitive to TSG-3', whereas this C-terminal TSG101 fragment potently impairs the budding of EIAV when it is rendered PTAP or PPPY dependent; (iii) budding of all EIAV clones is blocked by dominant negative Vps4; and (iv) EIAV/WT release is not impaired by proteasome inhibitors, while EIAV/PTAP and EIAV/PPPY release is strongly disrupted by these compounds. These findings highlight intriguing similarities and differences in host factor utilization by retroviral L domains and suggest that the insensitivity of EIAV to proteasome inhibitors is conferred by the L domain itself and not by determinants in Gag outside the L domain.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenosine Triphosphatases / antagonists & inhibitors
  • Amino Acid Motifs
  • Animals
  • Cell Line
  • Cysteine Endopeptidases
  • Gene Expression Regulation, Viral*
  • Gene Products, gag / chemistry*
  • Gene Products, gag / genetics
  • Gene Products, gag / metabolism*
  • Humans
  • Infectious Anemia Virus, Equine / chemistry
  • Infectious Anemia Virus, Equine / growth & development*
  • Infectious Anemia Virus, Equine / pathogenicity
  • Multienzyme Complexes / antagonists & inhibitors*
  • Protease Inhibitors / pharmacology*
  • Proteasome Endopeptidase Complex
  • Transfection
  • Virion / genetics
  • Virion / metabolism*


  • Gene Products, gag
  • Multienzyme Complexes
  • Protease Inhibitors
  • Cysteine Endopeptidases
  • Proteasome Endopeptidase Complex
  • Adenosine Triphosphatases