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Journal of Virology, June 1999, p. 4748-4754, Vol. 73, No. 6
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Role of the Individual Interferon Systems and Specific Immunity in Mice in Controlling Systemic Dissemination of Attenuated Pseudorabies Virus Infection

Philipp Grob,1 Virgil E. C. J. Schijns,2 Maries F. van den Broek,3 Silvie P. J. Cox,2 Mathias Ackermann,1 and Mark Suter1,*

Institute of Virology1 and Institute of Experimental Immunology,3 University of Zürich, CH-8057 Zürich, Switzerland, and Department of Vaccine Technology and Immunology, Intervet Int. B. V., 5830 AA Boxmer, The Netherlands2

Received 16 November 1998/Accepted 11 March 1999

The importance of each of the two interferon (IFN) systems in impeding herpesvirus replication and in stimulating virus-specific lymphocytes to control an acute systemic infection is not completely understood. To further our knowledge, pseudorabies virus, attenuated by deletion of the glycoprotein E gene to impair its neurovirulence and by deletion of the thymidine kinase gene (gE-TK-PRV), was used to infect wild-type 129Sv/Ev and congenic mice with immune system-associated genetic deficiencies. Mice with mature B and T lymphocytes but lacking either one or both functional receptors for members of each of the two IFN families were infected with gE-TK-PRV. At 3 and 7 but not 14 days after infection, replicating gE-TK-PRV could be isolated only from livers or spleens of mice lacking the receptors for both IFN families, and these mice survived the infection. Therefore, functional IFN receptors were not required to induce a protective immune response against an acute infection with gE-TK-PRV. Furthermore, PRV-specific antibodies of all immunoglobulin G isotypes were produced in these mice. Mice without mature B and T lymphocytes and lacking either one or both functional receptors for members of each of the two IFN families were also infected with gE-TK-PRV. Three days after infection, replicating virus could be isolated only from mice lacking both mature B and T lymphocytes and functional IFN receptors, and these mice were not able to clear the virus. We present evidence that mice with an intact gamma IFN system but without mature B and T cells were able to prevent systemic dissemination of gE-TK-PRV.

* Corresponding author. Mailing address: Institute of Virology, University of Zürich, Winterthurerstr. 266a, CH-8057 Zürich, Switzerland. Phone: 41 1 635 8717. Fax: 41 1 635 8911. E-mail: msuter{at}vetvir.unizh.ch.

Journal of Virology, June 1999, p. 4748-4754, Vol. 73, No. 6
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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