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Journal of virology2002; 76(6); 2641-2647; doi: 10.1128/jvi.76.6.2641-2647.2002

Budding of equine infectious anemia virus is insensitive to proteasome inhibitors.

Abstract: The only retrovirus protein required for the budding of virus-like particles is the Gag protein; however, recent studies of Rous sarcoma virus (RSV) and human immunodeficiency virus have suggested that modification of Gag with ubiquitin (Ub) is also required. As a consequence, the release of these viruses is reduced in the presence of proteasome inhibitors, which indirectly reduce the levels of free Ub within the cell. Here we show that the budding of equine infectious anemia virus (EIAV) from infected equine cells is largely unaffected by these drugs, although use of one inhibitor (MG-132) resulted in a dramatic block to proteolytic processing of Gag. This lack of sensitivity was also observed in transiently transfected avian cells under conditions that greatly reduce RSV budding. Moreover, insensitivity was observed when the EIAV Gag protein was expressed in the absence of all the other virus products, indicating that they are not required for this phenotype. An activity that enables EIAV to tolerate exposure to proteasome inhibitors was mapped to the C-terminal p9 sequence, as demonstrated by the ability of an RSV Gag-p9 chimera to bud in the presence of the drugs. Intriguingly, the p9 sequence contains a short sequence motif that is similar to a surface-exposed helix of Ub, suggesting that EIAV Gag may have captured a function that allows it to bypass the need for ubiquitination. Thus, the mechanism of EIAV budding may not be substantially different from that of other retroviruses, even though it behaves differently in the presence of proteasome inhibitors.
Publication Date: 2002-02-28 PubMed ID: 11861830PubMed Central: PMC135976DOI: 10.1128/jvi.76.6.2641-2647.2002Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • U.S. Gov't
  • P.H.S.

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research study explores the budding process of equine infectious anemia virus (EIAV) and its insensitivity to proteasome inhibitors, when compared with other retroviruses. The study indicates the virus may have a unique function allowing it to bypass the need for ubiquitination, a common cellular process necessary for other retroviruses.

Introduction and Methodology

  • The study begins by setting the context that Gag Protein is the sole retrovirus protein necessary for budding of virus-like particles, but recent studies also suggest the need for Gag modification with a protein called ubiquitin (Ub).
  • The release of other retroviruses such as Rous sarcoma virus (RSV) and human immunodeficiency virus (HIV) is reduced in the presence of proteasome inhibitors since these inhibitors reduce free Ub within the cell. The researchers aimed to explore how EIAV budding behaved in the presence of such inhibitors.
  • The research method involved infecting equine cells with EIAV and applying proteasome inhibitors to observe any changes.

Findings

  • Surprisingly, the budding of EIAV was largely unaffected by these drugs, except for MG-132, which blocked the processing of the Gag protein. This indicated a contrast in EIAV behavior compared to the RSV and HIV.
  • Similar results were obtained with avian cells transiently transfected with the virus, meaning the other virus products aren’t necessary for this phenotype.
  • Further analysis located the insensitivity to the C-terminal p9 sequence, suggesting a unique function in EIAV facilitating survival in the presence of proteasome inhibitors.
  • Interestingly, this p9 sequence had similarities to a short sequence motif in Ub, indicating the possibility that EIAV ‘borrowed’ this function to bypass the need for ubiquitination.

Conclusion

  • Despite this differential behavior in the presence of proteasome inhibitors, the study concludes that the budding mechanism of EIAV may not be vastly different from other retroviruses.
  • The research could have significant implications for the treatment of EIAV, as well as in the broader understanding of how different viruses manipulate cell mechanisms to ensure their proliferation.

Cite This Article

APA
Patnaik A, Chau V, Li F, Montelaro RC, Wills JW. (2002). Budding of equine infectious anemia virus is insensitive to proteasome inhibitors. J Virol, 76(6), 2641-2647. https://doi.org/10.1128/jvi.76.6.2641-2647.2002

Publication

ISSN: 0022-538X
NlmUniqueID: 0113724
Country: United States
Language: English
Volume: 76
Issue: 6
Pages: 2641-2647

Researcher Affiliations

Patnaik, Akash
  • Department of Microbiology and Immunology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA.
Chau, Vincent
    Li, Feng
      Montelaro, Ronald C
        Wills, John W

          MeSH Terms

          • Animals
          • Cell Line
          • Cysteine Endopeptidases
          • Enzyme Inhibitors / pharmacology
          • Gene Products, gag / metabolism
          • Infectious Anemia Virus, Equine / drug effects
          • Infectious Anemia Virus, Equine / genetics
          • Infectious Anemia Virus, Equine / physiology
          • Multienzyme Complexes / antagonists & inhibitors
          • Proteasome Endopeptidase Complex
          • Transfection
          • Ubiquitins / metabolism

          Grant Funding

          • R01 CA047482 / NCI NIH HHS
          • R01 CA049296 / NCI NIH HHS
          • CA47484 / NCI NIH HHS
          • CA49296 / NCI NIH HHS
          • R37 CA047482 / NCI NIH HHS

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