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Journal of Virology, May 2002, p. 4287-4293, Vol. 76, No. 9
0022-538X/02/$04.00+0 DOI: 10.1128/JVI.76.9.4287-4293.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.
Respiratory Syncytial Virus (RSV) Nonstructural (NS) Proteins as Host Range Determinants: a Chimeric Bovine RSV with NS Genes from Human RSV Is Attenuated in Interferon-Competent Bovine Cells
Birgit Bossert and Karl-Klaus Conzelmann*
Max von Pettenkofer Institute and Gene Center, Ludwig Maximilians University Munich, D-81377 Munich, Germany
Received 14 November 2001/
Accepted 4 February 2002
Bovine respiratory syncytial virus (BRSV) escapes from cellular responses to alpha/beta interferon (IFN-
/ß) by a concerted action of the two viral nonstructural proteins, NS1 and NS2. Here we show that the NS proteins of human RSV (HRSV) are also able to counteract IFN responses and that they have the capacity to protect replication of an unrelated rhabdovirus. Even combinations of BRSV and HRSV NS proteins showed a protective activity, suggesting common mechanisms and cellular targets of HRSV and BRSV NS proteins. Although able to cooperate, NS proteins from BRSV and HRSV showed differential protection capacity in cells from different hosts. A chimeric BRSV with HRSV NS genes (BRSV h1/2) was severely attenuated in bovine IFN competent MDBK and Klu cells, whereas it replicated like BRSV in IFN-incompetent Vero cells or in IFN-competent human HEp-2 cells. After challenge with exogenous IFN-
, BRSV h1/2 was better protected than wild-type BRSV in human HEp-2 cells. In contrast, in cells of bovine origin, BRSV h1/2 was much less resistant to exogenous IFN than wild-type BRSV. These data demonstrate that RSV NS1 and NS2 proteins are major determinants of host range. The differential IFN escape capacity of RSV NS proteins in cells from different hosts provides a basis for rational development of attenuated live RSV vaccines.
* Corresponding author: Mailing address: Max von Pettenkofer Institute and Gene Center, Feodor-Lynen-Str. 25, D-81377 Munich, Germany. Phone: 49 89 2180 6851. Fax: 49 89 2180 6899. E-mail: conzelma{at}lmb.uni-muenchen.de.
Journal of Virology, May 2002, p. 4287-4293, Vol. 76, No. 9
0022-538X/02/$04.00+0 DOI: 10.1128/JVI.76.9.4287-4293.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.
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Copyright © 2002 by the American Society for Microbiology. All rights reserved.