Immune responses and cytokine induction in the development of severe hepatitis during acute infections with murine cytomegalovirus

Salivary gland-derived murine cytomegalovirus (SGV) infections of mice have been widely used as models of human cytomegalovirus infections and in the study of CMV biology. Still, many aspects of SGV pathogenesis are not clear ly defined. Fatal and non-fatal SGV infections were investigated to charact erize pathogenetic correlates of mortality and to assess the role of the im mune response in disease progression. Suppression of immune responses was o bserved in both lethal and sublethal infections. Depletion of immune cell p opulations in spleen, however, correlated with severe CMV-induced hepatitis and mortality. In addition, T cell depletion studies indicated a requireme nt for this immune cell subset in control of liver damage and survival of i nfected mice. Examination of cytokine responses revealed a previously undes cribed shock-like syndrome in lethally-infected mice characterized by high levels of tumor necrosis factor rx and interferon gamma. Furthermore, the s ites of tumor necrosis factor or gene induction did not strictly correlate with either viral load or the sites of tissue damage during infection. Take n together, these findings define the pathogenetic progression of disease a s it relates to disease outcome and suggests that organ-specific difference s in cytokine induction play a significant role in the late stages of acute lethal MCMV infections.