Author/Editor		Trgovčič, J; Štimac, D; Polić, B; Krmpotić, A; Pernjak-Pugel, E; Tomac, J; Hasan, M; Wraber, B; Jonjić, S
Title		Immune responses and cytokine induction in the development of severe hepatitis during acute infections with murine cytomegalovirus
Type		članek
Source		Arch Virol
Vol. and No.		Letnik 145
Publication year		2000
Volume		str. 2601-18
Language		eng
Abstract		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 clearly defined. Fatal and non-fatal SGV infections were investigated to characterize pathogenetic correlates of mortality and to assess the role of the immune response in disease progression. Suppression of immune responses was observed in both lethal and sublethal infections. Depletion of immune cell populations in spleen, however, correlated with severe CMV induced hepatitis and mortality. In addition, T cell depletion studies indicated a requirement for this immune cell subset in control of liver damage and survival of infected mice. Examination of cytokine responses revealed a previously undescribed shock-like syndrome in lethally-infected mice characterized by high levels of tumor necrosis factor alpha and interferon gamma. Furthermore, the sites of tumor necrosis factor a gene induction did not strictly correlate with either viral load or the sites of tissue damage during infection. Taken together, these findings define the pathogenetic progression of disease as it relates to disease outcome and suggests that organ-specific differences in cytokine induction play a significant role in the late stages of acute lethal MCMV infections.
Descriptors		MUROMEGALOVIRUS HEPATITIS INTERFERON TYPE II TUMOR NECROSIS FACTOR DISEASE MODELS, ANIMAL DISEASE PROGRESSION MICE, INBRED BALB C IMMUNOHISTOCHEMISTRY ASPARTATE AMINOTRANSFERASE ALANINE AMINOTRANSFERASE LACTATE DEHYDROGENASE POLYMERASE CHAIN REACTION T-LYMPHOCYTE SUBSETS VIRULENCE VIRUS REPLICATION