Cytomegalovirus M43 gene modulates T helper cell response

Role of viral genes in modulating T helper 1 (Th1) and T helper 2 (Th2) balance is of principal interest in the study of cytomegalovirus (CMV) immunity. Murine CMV (MCMV) mutants were used to explore a possible mechanism for the ability of virus to induce a predominant Th1 response and to suppress Th2 response by examining the production of Th1 (IFN-gamma, IL-2) and Th2 (IL-4, IL-10) cytokines by the splenocytes of mice infected with wild type (WT) and MCMV mutants. Results (n=6) show that as compared with WT, the MCMV mutant with specific disruption of M43 gene upregulates the production of IL-4 (P=0.0002) and to a lesser extent IL-10 (P=0.015) at 14 days post infection. This indicates that M43 gene may play a role in suppressing Th2 (IL-4) production, especially in the later stage of infection. The IL-4 and IL-10 production during infection with M43 mutant occurs in the presence of a strong IFN-gamma (Th1) response, overriding the cross-regulatory effects of these cytokines within the Th1/Th2 paradigm and suggesting that the predominant response during CMV infection is still a Th1 type response.