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Journal of Virology, September 2002, p. 9218-9224, Vol. 76, No. 18
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.18.9218-9224.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Cleavage at the Furin Consensus Sequence RAR/KR109 and Presence of the Intervening Peptide of the Respiratory Syncytial Virus Fusion Protein Are Dispensable for Virus Replication in Cell Culture

Gert Zimmer,1 Karl-Klaus Conzelmann,2 and Georg Herrler1*

Institut für Virologie, Tierärztliche Hochschule Hannover, D-30559 Hannover,1 Max-von-Pettenkofer-Insitut and Genzentrum der Ludwig-Maximillians-Universität, D-81377 Munich, Germany2

Received 22 April 2002/ Accepted 17 June 2002

Proteolytic processing of the respiratory syncytial virus F (fusion) protein results in the generation of the disulfide-linked subunits F1 and F2 and in the release of pep27, a glycopeptide originally located between the two furin cleavage sites FCS-1 (RKRR136) and FCS-2 (RAR/KR109). We made use of reverse genetics to study the importance of FCS-2 and of pep27 for BRSV replication in cell culture. Replacement of FCS-2 in the F protein of recombinant viruses by either of the sequences NANR109, RANN109 or SANN109, respectively, abolished proteolytic processing at this position, whereas the cleavage of FCS-1 was not affected. All mutants replicated in calf kidney and Vero cells in the absence of exogenous trypsin, although somewhat higher titers of BRSV containing the NANR109 or the RANN109 motif were achieved in the presence of trypsin. The virus mutants showed a reduced cytopathic effect which was lowest in the case of the SANN109 mutant. These findings demonstrate that cleavage at FCS-2 is dispensable for replication of respiratory syncytial virus in cell culture. A deletion mutant containing FCS-1 but lacking FCS-2 and most of pep27 replicated in cell culture as efficiently as the parental virus, indicating that this domain of the F protein is not essential for virus maturation and infectivity.

* Corresponding author. Mailing address: Institut für Virologie, Tierärztliche Hochschule, Hannover, Bünteweg 17, D-30559 Hannover, Germany. Phone: 49-511-953-8857. Fax: 49-511-953-8898. E-mail: Georg.Herrler{at}tiho-hannover.de.

Journal of Virology, September 2002, p. 9218-9224, Vol. 76, No. 18
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.18.9218-9224.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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