Acute murine cytomegalovirus infection: a model for determining antiviral activity against CMV induced hepatitis.
Acute intraperitoneal infection of weanling BALB/c mice with murine cytomegalovirus (MCMV) resulted in an inoculum titer-dependent weight loss, mortality and elevation of plasma transaminases (ALT: alanine transaminase and AST: aspartate transaminase). Three days post infection (p.i.) with 10(4.85) plaque forming units (pfu) there was 90% mortality with a mean death day p.i. of 4.1 +/- 0.2. Plasma levels of ALT and AST were elevated 24- and 15-fold, respectively. Organ titers of virus (log10 pfu/g tissue) were 6.16 in the liver, 6.05 in the spleen, 4.0-4.7 in the lung, heart, kidney and intestine and undetectable in the muscle and brain. Organ concentrations (units/g wet-weight) of ALT were highest in the liver, whilst for AST the highest levels were found in the heart. The concentrations of ALT but not AST were reduced (35-55%) in the infected liver; the concentrations of ALT and AST were not changed in other infected organs. There were excellent correlations (r > 0.95) between viral titers in the liver, increases of plasma ALT and depletion of liver ALT. HPMPC and ganciclovir administered either p.o. or s.c. reduced mortality, increases in plasma transaminases and viral burdens in the liver and prevented depletion of liver ALT. HPMPC was approximately 10-fold more potent than ganciclovir. These results strongly suggest that intraperitoneal infection of the BALB/c mouse with MCMV represents an animal model of CMV hepatitis that can be monitored by measuring plasma ALT.
Bolger
G
G
Department of Biological Sciences, Boehringer Ingelheim (Canada) Limited, Laval, Quebec, Canada.
Lapeyre
N
N
Rhéaume
M
M
Kibler
P
P
Bousquet
C
C
Garneau
M
M
Cordingley
M
M
D000410:Alanine Transaminase / Q000097:blood / Q000378:metabolism; D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D001219:Aspartate Aminotransferases / Q000097:blood / Q000378:metabolism; D001835:Body Weight; D000077404:Cidofovir; D003586:Cytomegalovirus Infections / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D003596:Cytosine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004195:Disease Models, Animal; D005260:Female; D015774:Ganciclovir / Q000627:therapeutic use*; D006524:Hepatitis, Viral, Animal / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D006566:Herpesviridae Infections / Q000188:drug therapy / Q000473:pathology / Q000821:virology; D008099:Liver / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D018146:Muromegalovirus / Q000187:drug effects / Q000502:physiology*; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000627:therapeutic use*; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D063065:Organophosphonates; D009943:Organophosphorus Compounds; D003596:Cytosine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000077404:Cidofovir; D015774:Ganciclovir