Patterns of Expression of Viral and Cytokine Gene Transcripts During Mouse Polyoma Virus Infection

Donald   R.   Drake; Leise      Knoepp; Jeffrey   K.   Actor; Aron   E.   Lukacher

Abstract

CD8+ cytotoxic T lymphocytes are critical for clearance of infection and prevention of tumors caused by mouse polyoma virus. High susceptibility to polyoma-induced tumors is manifested by neonatal inoculation of mice belonging to particular H-2κ haplotype inbred strains. We previously reported that tumor-susceptible mice generate polyoma-specific CD8+ T cells, but at a frequency approximately 20-fold lower than tumor-resistant H-2κ mice. To determine whether susceptibility or resistance may also be associated with a cytokine microenvironment conducive for promoting cellmediated (i.e., type 1 cytokines) or humoral (i.e., type 2 cytokines) immune responses, we used quantitative bioluminescence RT-PCR to measure in vivo message levels for viral proteins and cytokines during infection of neonatal mice. We found that the level of polyoma viral transcripts peaked higher and fell with significantly slower kinetics in tumor-susceptible mice than in tumor-resistant mice. Interestingly, message for VP1, the major viral capsid protein, persisted in multiple organs of mice of both susceptible and resistant strains, indicating chronic productive infection regardless of tumor susceptibility. IL-1β, IL-12, IL-2, IFN-γ, and IL-4 message levels were all higher in infected susceptible than resistant mice. Although both susceptible and resistant mice expressed transcripts for IFN-γ and IL- 4, the signature type 1 and type 2 cytokines, respectively, a dominance of IL-4 message, with concomitant drop in IFN-γ message, was seen only in the susceptible mice. These results suggest that a type 2 pattern of cytokine expression may contribute to susceptibility to polyoma virus tumorigenesis.

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