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Journal of Virology, May 2002, p. 4172-4180, Vol. 76, No. 9
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.9.4172-4180.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Amino-Terminal Precursor Sequence Modulates Canine Distemper Virus Fusion Protein Function

Veronika von Messling and Roberto Cattaneo*

Molecular Medicine Program, Mayo Clinic, Rochester, Minnesota 55905

Received 26 November 2001/ Accepted 4 February 2002

The fusion (F) proteins of most paramyxoviruses are classical type I glycoproteins with a short hydrophobic leader sequence closely following the translation initiation codon. The predicted reading frame of the canine distemper virus (CDV) F protein is more complex, with a short hydrophobic sequence beginning 115 codons downstream of the first AUG. To verify if the sequence between the first AUG and the hydrophobic region is translated, we produced a specific antiserum that indeed detected a short-lived F protein precursor that we named PreF0. A peptide resulting from PreF0 cleavage was identified and named Pre, and its half-life was measured to be about 30 min. PreF0 cleavage was completed before proteolytic activation of F0 into its F1 and F2 subunits by furin. To test the hypothesis that the Pre peptide may influence protein activity, we compared the function of F proteins synthesized with that peptide to that of F proteins synthesized with a shorter amino-terminal signal sequence. F proteins synthesized with the Pre peptide were more stable and less active. Thus, the Pre peptide modulates the function of the CDV F protein. Interestingly, a distinct two-hit activation process has been recently described for human respiratory syncytial virus, another paramyxovirus.

* Corresponding author. Mailing address: Molecular Medicine Program, Mayo Foundation, Guggenheim 1838, 200 First St. SW, Rochester, MN 55905. Phone: (507) 284-0171. Fax: (507) 266-2122. E-mail: cattaneo.roberto{at}mayo.edu.

Journal of Virology, May 2002, p. 4172-4180, Vol. 76, No. 9
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.9.4172-4180.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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