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Journal of Virology, April 2007, p. 4323-4330, Vol. 81, No. 8
0022-538X/07/$08.00+0     doi:10.1128/JVI.02279-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Degrons at the C Terminus of the Pathogenic but Not the Nonpathogenic Hantavirus G1 Tail Direct Proteasomal Degradation{triangledown}

Nandini Sen,1,2,3 Adrish Sen,1,2,3 and Erich R. Mackow1,2,3,4*

Molecular and Cellular Biology Graduate Program,1 Department of Medicine,2 Department of Molecular Genetics and Microbiology, State University of New York at Stony Brook, Stony Brook, New York 11794,3 Northport VA Medical Center, Northport, New York 117684

Received 17 October 2006/ Accepted 24 January 2007

Pathogenic hantaviruses cause two human diseases: hantavirus pulmonary syndrome (HPS) and hemorrhagic fever with renal syndrome (HFRS). The hantavirus G1 protein contains a long, 142-amino-acid cytoplasmic tail, which in NY-1 virus (NY-1V) is ubiquitinated and proteasomally degraded (E. Geimonen, I. Fernandez, I. N. Gavrilovskaya, and E. R. Mackow, J. Virol. 77: 10760-10768, 2003). Here we report that the G1 cytoplasmic tails of pathogenic Andes (HPS) and Hantaan (HFRS) viruses are also degraded by the proteasome and that, in contrast, the G1 tail of nonpathogenic Prospect Hill virus (PHV) is stable and not proteasomally degraded. We determined that the signals which direct NY-1V G1 tail degradation are present in a hydrophobic region within the C-terminal 30 residues of the protein. In contrast to that of PHV, the NY-1V hydrophobic domain directs the proteasomal degradation of green fluorescent protein and constitutes an autonomous degradation signal, or "degron," within the NY-1V G1 tail. Replacing 4 noncontiguous residues of the NY-1V G1 tail with residues present in the stable PHV G1 tail resulted in a NY-1V G1 tail that was not degraded by the proteasome. In contrast, changing a different but overlapping set of 4 PHV residues to corresponding NY-1V residues directed proteasomal degradation of the PHV G1 tail. The G1 tails of pathogenic, but not nonpathogenic, hantaviruses contain intervening hydrophilic residues within the C-terminal hydrophobic domain, and amino acid substitutions that alter the stability or degradation of NY-1V or PHV G1 tails result from removing or adding intervening hydrophilic residues. Our results identify residues that selectively direct the proteasomal degradation of pathogenic hantavirus G1 tails. Although a role for the proteasomal degradation of the G1 tail in HPS or HFRS is unclear, these findings link G1 tail degradation to viral pathogenesis and suggest that degrons within hantavirus G1 tails are potential virulence determinants.

* Corresponding author. Mailing address: Departments of Medicine and Molecular Genetics and Microbiology, HSC T17, Rm. 60, SUNY at Stony Brook, Stony Brook, NY 11794. Phone: (631) 444-2120. Fax: (631) 444-8886. E-mail: Erich.Mackow{at}stonybrook.edu

{triangledown} Published ahead of print on 31 January 2007.

Journal of Virology, April 2007, p. 4323-4330, Vol. 81, No. 8
0022-538X/07/$08.00+0     doi:10.1128/JVI.02279-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Estrada, D. F., Boudreaux, D. M., Zhong, D., St. Jeor, S. C., De Guzman, R. N. (2009). The Hantavirus Glycoprotein G1 Tail Contains Dual CCHC-type Classical Zinc Fingers. J. Biol. Chem. 284: 8654-8660 [Abstract] [Full Text]  
  • Alff, P. J., Sen, N., Gorbunova, E., Gavrilovskaya, I. N., Mackow, E. R. (2008). The NY-1 Hantavirus Gn Cytoplasmic Tail Coprecipitates TRAF3 and Inhibits Cellular Interferon Responses by Disrupting TBK1-TRAF3 Complex Formation. J. Virol. 82: 9115-9122 [Abstract] [Full Text]  


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