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

• Published in: Journal of virology Vol. 75; no. 1; pp. 52 - 60
• Main Authors: Iwashiro, M, Peterson, K, Messer, R J, Stromnes, I M, Hasenkrug, K J
• Format: Journal Article
• Language: English
• Published: 01-01-2001
• Subjects: CD4 antigen; Friend murine leukemia virus; g-Interferon; Retrovirus
• ISSN: 0022-538X

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 super(+) T cells play an essential role in keeping persistent retrovirus in check. The present in vitro experiments with a Friend virus-specific CD4 super(+) 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 super(+) 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.