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
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-
), which acts with two distinct mechanisms of antiviral activity. First, IFN-
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-
-mediated antiviral activity was an enhancement of CD4+ T-cell-mediated cytolytic
activity. We also found an in vivo role for IFN-
in the control of
persistent Friend virus infections. Neutralization of IFN-
in
persistently infected mice resulted in significantly increased levels
of virus in the spleen, and a significant percentage of
IFN-
-deficient mice were unable to maintain long-term control over
Friend virus infections.
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