A critical role of LAMP-1 in avian reovirus P10 degradation associated with inhibition of apoptosis and virus release

A critical role of LAMP-1 in avian reovirus P10 degradation associated with inhibition of... Avian reovirus (ARV) causes viral arthritis, chronic respiratory diseases, retarded growth and malabsorption syndrome. The ARV p10 protein, a viroporin responsible for the induction of cell syncytium formation and apoptosis, is rapidly degraded in host cells. However, the mechanism of p10 degradation and its relevance are still unclear. We report here the identification of cellular lysosome-associated membrane protein 1 (LAMP-1) as an interaction partner of p10 by yeast two-hybrid screening, immunoprecipitation and confocal microscopy assays. We found that rapid degradation of p10 was associated with ubiquitination. Importantly, ARV p10 degradation in host cells could be completely abolished by knockdown of LAMP-1 by siRNA, indicating that LAMP-1 is required for ARV p10 degradation in host cells. In contrast, overexpression of LAMP-1 facilitated p10 degradation. Furthermore, knockdown of LAMP-1 allowed p10 accumulation, enhancing p10-induced apoptosis and viral release. Thus, LAMP-1 plays a critical role in ARV p10 degradation associated with inhibition of apoptosis and viral release. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Virology Springer Journals

A critical role of LAMP-1 in avian reovirus P10 degradation associated with inhibition of apoptosis and virus release

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Publisher
Springer Vienna
Copyright
Copyright © 2016 by Springer-Verlag Wien
Subject
Biomedicine; Virology; Medical Microbiology; Infectious Diseases
ISSN
0304-8608
eISSN
1432-8798
D.O.I.
10.1007/s00705-015-2731-5
Publisher site
See Article on Publisher Site

Abstract

Avian reovirus (ARV) causes viral arthritis, chronic respiratory diseases, retarded growth and malabsorption syndrome. The ARV p10 protein, a viroporin responsible for the induction of cell syncytium formation and apoptosis, is rapidly degraded in host cells. However, the mechanism of p10 degradation and its relevance are still unclear. We report here the identification of cellular lysosome-associated membrane protein 1 (LAMP-1) as an interaction partner of p10 by yeast two-hybrid screening, immunoprecipitation and confocal microscopy assays. We found that rapid degradation of p10 was associated with ubiquitination. Importantly, ARV p10 degradation in host cells could be completely abolished by knockdown of LAMP-1 by siRNA, indicating that LAMP-1 is required for ARV p10 degradation in host cells. In contrast, overexpression of LAMP-1 facilitated p10 degradation. Furthermore, knockdown of LAMP-1 allowed p10 accumulation, enhancing p10-induced apoptosis and viral release. Thus, LAMP-1 plays a critical role in ARV p10 degradation associated with inhibition of apoptosis and viral release.

Journal

Archives of VirologySpringer Journals

Published: Apr 1, 2016

References

  • Avian reovirus: structure and biology
    Benavente, J; Martinez-Costas, J
  • Apoptosis induction by avian reovirus through p53 and mitochondria-mediated pathway
    Chulu, JL; Lee, LH; Lee, YC; Liao, SH; Lin, FL; Shih, WL; Liu, HJ
  • Reovirus-induced apoptosis: a minireview
    Clarke, P; Tyler, KL
  • Roles of LAMP-1 and LAMP-2 in lysosome biogenesis and autophagy
    Eskelinen, EL
  • Avian reovirus S1133-induced DNA damage signaling and subsequent apoptosis in cultured cells and in chickens
    Lin, PY; Liu, HJ; Chang, CD; Chang, CI; Hsu, JL; Liao, MH; Lee, JW; Shih, WL
  • Retardation of cell growth by avian reovirus p17 through the activation of p53 pathway
    Liu, HJ; Lin, PY; Lee, JW; Hsu, HY; Shih, WL
  • Critical role of eukaryotic elongation factor 1 alpha 1 (EEF1A1) in avian reovirus sigma-C-induced apoptosis and inhibition of viral growth
    Zhang, Z; Lin, W; Li, X; Cao, H; Wang, Y; Zheng, SJ

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