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Journal of Virology, August 2002, p. 7430-7443, Vol. 76, No. 15
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.15.7430-7443.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Addition of Exogenous Protease Facilitates Reovirus Infection in Many Restrictive Cells

Joseph W. Golden, Jessica Linke, Stephen Schmechel, Kara Thoemke, and Leslie A. Schiff*

Department of Microbiology, University of Minnesota, Minneapolis, Minnesota 55455

Received 31 October 2001/ Accepted 26 April 2002

Virion uncoating is a critical step in the life cycle of mammalian orthoreoviruses. In cell culture, and probably in extraintestinal tissues in vivo, reovirus virions undergo partial proteolysis within endosomal or/or lysosomal compartments. This process converts the virion into a form referred to as an intermediate subvirion particle (ISVP). In natural enteric reovirus infections, proteolytic uncoating takes place extracellularly within the intestinal lumen. The resultant proteolyzed particles, unlike intact virions, have the capacity to penetrate cell membranes and thereby gain access to cytoplasmic components required for viral gene expression. We hypothesized that the capacity of reovirus outer capsid proteins to be proteolyzed is a determinant of cellular host range. To investigate this hypothesis, we asked if the addition of protease to cell culture medium would expand the range of cultured mammalian cell lines that can be productively infected by reoviruses. We identified many transformed and nontransformed cell lines, as well as primary cells, that restrict viral infection. In several of these restrictive cells, virion uncoating is inefficient or blocked. Addition of proteases to the cell culture medium generates ISVP-like particles and promotes viral growth in nearly all cell lines tested. Interestingly, we found that some cell lines that restrict reovirus uncoating still express mature cathepsin L, a lysosomal protease required for virion disassembly in murine L929 cells. This finding suggests that factors in addition to cathepsin L are required for efficient intracellular proteolysis of reovirus virions. Our results demonstrate that virion uncoating is a critical determinant of reovirus cellular host range and that many cells which otherwise support productive reovirus infection cannot efficiently mediate this essential early step in the virus life cycle.

* Corresponding author. Mailing address: Department of Microbiology, University of Minnesota, Mayo Mail Code 196, 420 Delaware St. S.E., Minneapolis, MN 55455. Phone: (612) 624-9933. Fax: (612) 626-0623. E-mail: schiff{at}lenti.med.umn.edu.

Journal of Virology, August 2002, p. 7430-7443, Vol. 76, No. 15
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.15.7430-7443.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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