VSV infection of resting and activated T lymphocytes

Abstract

Resting T lymphocytes are uniquely resistant to VSV even at high multiplicities of infection but they can be rendered fully permissive for VSV replication following in-vitro activation with monoclonal anti-CD3 and PMA with ionomycin. The block to VSV replication is at the level of viral RNA production and is independent of transcription following infection. T lymphocytes must be activated before infection for at least 24 hours to be rendered susceptible to VSV and transcription is an absolute requirement during this process. Fusion of resting and activated T cells results in a resistant cell indicating that the resistant state is dominant. Resting T cells do not produce interferon (IFN) alpha or beta in response to VSV infection whereas activated T cells produce both but have a down modulated response to the antiviral activity of type I IFNs. Gene expression array analysis demonstrates that the interferon response factors, IRF-4 and IRF-8, are up regulated during activation and a number of interferon stimulating genes (ISG), including ISG20, MxA and GBP-1 are down regulated during activation. IRF-4 and IRF-8 have both been described to bind to and inhibit transactivation from the interferon stimulated response elements (ISRE) in the promoters of a number of ISGs and this could explain the down modulated antiviral response to type I IFNs in activated T cells. The IFN-independent constitutive expression of these ISGs in resting T cells is a possible mechanism for their unique resistance to VSV replication.