Patterns of expression of viral and cytokine gene transcripts during mousepolyoma virus infection

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 belong ing to particular H-2(k) haplotype inbred strains. We previously reported t hat tumor-susceptible mice generate polyoma-specific CD8+ T cells, but at a frequency approximately 20-fold lower than tumor-resistant H-2k mice. To d etermine 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 th at the level of polyoma viral transcripts peaked higher and fell with signi ficantly slower kinetics in tumor-susceptible mice than in tumor-resistant mice. Interestingly, message for VP1, the major viral capsid protein, persi sted in multiple organs of mice of both susceptible and resistant strains, indicating chronic productive infection regardless of tumor susceptibility. IL-1 beta, IL-12, IL-2, IFN-gamma, and IL-4 message levels were all higher in infected susceptible than resistant mice. Although both susceptible and resistant mice expressed transcripts for IFN-gamma and IL-4, the signature type 1 and type 2 cytokines, respectively, a dominance of IL-4 message, wi th concomitant drop in IFN-gamma message, was seen only in the susceptible mice. These results suggest that a type 2 pattern of cytokine expression ma y contribute to susceptibility to polyoma virus tumorigenesis.