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Journal of Virology, July 2000, p. 5896-5901, Vol. 74, No. 13
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Additive Effect of Neutralizing Antibody and Antiviral Drug Treatment in Preventing Virus Escape and Persistence

Peter Seiler,* Beatrice M. Senn, Paul Klenerman,dagger Ulrich Kalinke,Dagger Hans Hengartner, and Rolf M. Zinkernagel

Department of Pathology, Institute of Experimental Immunology, University of Zurich, CH-8091 Zurich, Switzerland

Received 30 December 1999/Accepted 29 March 2000

Poorly cytopathic or noncytopathic viruses can escape immune surveillance and establish a chronic infection. Here we exploited the strategy of combining antiviral drug treatment with the induction of a neutralizing antibody response to avoid the appearance of neutralization-resistant virus variants. Despite the fact that H25 immunoglobulin transgenic mice infected with lymphocytic choriomeningitis virus mounted an early neutralizing antibody response, the virus escaped from neutralization and persisted. After ribavirin treatment of H25 transgenic mice, the appearance of neutralization-resistant virus was prevented and virus was cleared. Thus, the combination of virus-neutralizing antibodies and chemotherapy efficiently controlled the infection, whereas each defense line alone did not. Similar additive effects may be unexpectedly efficient and beneficial in humans after infections with persistent viruses such as hepatitis C virus and hepatitis B virus and possibly human immunodeficiency virus.

* Corresponding author. Present address: Max-Planck-Institut für Infektionsbiologie, Monbijoustr. 2, D-10117 Berlin, Germany. Phone: 49-30-28460-525. Fax: 49-30-28460-503. E-mail: seiler{at}mpiib-berlin.mpg.de.

dagger Present address: Nuffield Department of Clinical Medicine, John Radcliffe Hospital, Oxford, United Kingdom.

Dagger Present address: EMBL Mouse Biology Programme, Adriano Buzzati-Traverso Campus, Monterotondo, Rome, Italy.

Journal of Virology, July 2000, p. 5896-5901, Vol. 74, No. 13
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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