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Journal of Virology, March 2002, p. 2225-2232, Vol. 76, No. 5
0022-538X/02/$04.00+0     DOI: 10.1128/jvi.76.5.2225-2232.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Temporal Effects of Gamma Interferon Deficiency on the Course of Friend Retrovirus Infection in Mice

*** Ingunn M. Stromnes,1 Ulf Dittmer,2 Ton N. M. Schumacher,3 Koen Schepers,3 Ronald J. Messer,1 Leonard H. Evans,1 Karin E. Peterson,1 Brent Race,1 and Kim J. Hasenkrug1*

Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana 59840,1 Institut für Virologie der Universität Würzburg, Würzburg, Germany ,2 Department of Immunology, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands3

Received 24 August 2001/ Accepted 16 November 2001

The current studies demonstrate complex and seemingly contradictory effects by gamma interferon (IFN-{gamma}) on Friend virus (FV) infection. Both temporal and tissue-specific effects were observed. During the first week of infection, IFN-{gamma}-deficiency caused increased levels of FV infection in multiple tissues. Surprisingly, however, by 2 weeks postinfection, IFN-{gamma}-deficient mice had significantly lower levels of infection in both the spleen and bone marrow compared to wild-type mice. The rapid reduction of virus in the IFN-{gamma}-deficient mice correlated with a more rapid virus-neutralizing antibody response than was observed in the wild-type mice. Furthermore, the virus-neutralizing antibody response in wild-type mice could be accelerated by ablation of their IFN-{gamma} response. Although the IFN-{gamma}-deficient mice developed an accelerated virus-neutralizing antibody response, they did not class-switch to immunoglobulin G class immunoglobulins nor could they maintain long-term virus-neutralizing antibody titers. Eventually, all of the IFN-{gamma}-deficient mice failed to keep persistent virus in check and developed fatal FV-induced erythroleukemia.

* Corresponding author. Mailing address: Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840. Phone: (406) 363-9310. Fax: (406) 363-9286. E-mail: khasenkrug{at}nih.gov.

Journal of Virology, March 2002, p. 2225-2232, Vol. 76, No. 5
0022-538X/02/$04.00+0     DOI: 10.1128/jvi.76.5.2225-2232.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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