Increased susceptibility to pentobarbital following mouse cytomegalovirus infection: relative roles of viral-induced interferon and viral infection of the liver.
The purpose of this study was to determine the relative roles of viral-induced interferon (IFN) and viral infection of the liver in mouse cytomegalovirus (MCMV)-induced depression of cytochrome P-450 (cyt P-450) levels and enhancement of pentobarbital-induced sleeping time (PEN-ST). This was done by establishing the temporal relationship among the IFN response, viral infection of the liver, suppression of cyt P-450 levels, and enhancement of PEN-ST, by determining the effect of anti-IFN antibody treatment on all of these responses, and by manipulating factors known to influence viral pathogenesis and host response to virus such as animal age, virulence of the virus, and dose of virus. In general, manipulation of these factors toward increased stimulation of host immune responses resulted in greater depression of cyt P-450. The data are consistent with the hypothesis that some IFN-dependent mechanism may have contributed to the effects of MCMV infection on both cyt P-450 levels and PEN-ST; however, the temporal relationship among the various responses measured following viral infection suggested that the effect of the IFN response may be indirect and due to modulation of other host defense mechanisms. Use of anti-IFN antisera to definitively establish a role for IFN in the effects observed here proved unsuccessful. Effects on PEN-ST and cyt P-450 levels did not appear to be related to the magnitude of infection in the liver.(ABSTRACT TRUNCATED AT 250 WORDS)
Catignani
J C
JC
Department of Parasitology, School of Public Health, University of North Carolina, Chapel Hill 27599.
Ménache
M G
MG
Selgrade
M K
MK
D000375:Aging / Q000276:immunology; D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003587:Cytomegalovirus / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000378:metabolism*; D007372:Interferons / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D008107:Liver Diseases / Q000209:etiology / Q000378:metabolism*; D051379:Mice; D010424:Pentobarbital / Q000494:pharmacology*; D012890:Sleep / Q000187:drug effects
D000906:Antibodies; D007372:Interferons; D003577:Cytochrome P-450 Enzyme System; D010424:Pentobarbital