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(American Journal of Pathology. 2002;161:2195-2207.)
© 2002 American Society for Investigative Pathology

Regular Articles

Replication and Clearance of Respiratory Syncytial Virus

Apoptosis Is an Important Pathway of Virus Clearance after Experimental Infection with Bovine Respiratory Syncytial Virus

Birgitte Viuff*, Kirsten Tjørnehøj{dagger}, Lars E. Larsen{ddagger}, Christine M. Røntved§, Åse Uttenthal{dagger}, Leif Rønsholt{dagger} and Soren Alexandersen

From the Department of Pharmacology and Pathobiology,* The Royal Veterinary and Agricultural University, Frederiksberg, Denmark; the Danish Veterinary Institute,{dagger} Lindholm, Denmark; the Danish Veterinary Institute,{ddagger} Copenhagen, Denmark; the Danish Institute of Agricultural Science,§ Tjele, Denmark; and the Pirbright Laboratory, Institute for Animal Health, Pirbright, United Kingdom

Human respiratory syncytial virus is an important cause of severe respiratory disease in young children, the elderly, and in immunocompromised adults. Similarly, bovine respiratory syncytial virus (BRSV) is causing severe, sometimes fatal, respiratory disease in calves. Both viruses are pneumovirus and the infections with human respiratory syncytial virus and BRSV have similar clinical, pathological, and epidemiological characteristics. In this study we used experimental BRSV infection in calves as a model of respiratory syncytial virus infection to demonstrate important aspects of viral replication and clearance in a natural target animal. Replication of BRSV was demonstrated in the luminal part of the respiratory epithelial cells and replication in the upper respiratory tract preceded the replication in the lower respiratory tract. Virus excreted to the lumen of the respiratory tract was cleared by neutrophils whereas apoptosis was an important way of clearance of BRSV-infected epithelial cells. Neighboring cells, which probably were epithelial cells, phagocytized the BRSV-infected apoptotic cells. The number of both CD4+ and CD8+ T cells increased during the course of infection, but the T cells were not found between the epithelial cells of the bronchi up until apoptosis was no longer detected, thus in the bronchi there was no indication of direct contact-dependent T-cell-mediated cytotoxicity in the primary infection.




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