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Journal of Virology, January 2001, p. 52-60, Vol. 75, No. 1
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.1.52-60.2001

CD4+ T Cells and Gamma Interferon in the Long-Term Control of Persistent Friend Retrovirus Infection

Michihiro Iwashiro, Karin Peterson, Ronald J. Messer, Ingunn M. Stromnes, and Kim J. Hasenkrug*

Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana 59840

Received 2 August 2000/Accepted 25 September 2000

We have used the Friend virus model to determine the basic mechanisms by which the immune system can control persistent retroviral infections. Previously we showed that CD4+ T cells play an essential role in keeping persistent retrovirus in check. The present in vitro experiments with a Friend virus-specific CD4+ T-cell clone revealed that these cells produce gamma interferon (IFN-gamma ), which acts with two distinct mechanisms of antiviral activity. First, IFN-gamma had a direct inhibitory effect on virus production. This inhibitory effect was noncytolytic and, interestingly, was not associated with decreased cell surface expression of viral antigens. The second mechanism of IFN-gamma -mediated antiviral activity was an enhancement of CD4+ T-cell-mediated cytolytic activity. We also found an in vivo role for IFN-gamma in the control of persistent Friend virus infections. Neutralization of IFN-gamma in persistently infected mice resulted in significantly increased levels of virus in the spleen, and a significant percentage of IFN-gamma -deficient mice were unable to maintain long-term control over Friend virus infections.

* Corresponding author. Mailing address: Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 903 South 4th St., Hamilton, MT 59840. Phone: (406) 363-9310. Fax: (406) 363-9286. E-mail: KHasenkrug{at}nih.gov.

Journal of Virology, January 2001, p. 52-60, Vol. 75, No. 1
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.1.52-60.2001


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