Suppression of infectious virus spread to the liver by foscarnet following lethal infection of acyclovir-resistant herpes simplex virus type 2 in mice.
Patients with the acquired immune deficiency syndrome (AIDS) occasionally develop hepatitis, pneumonia or esophagitis due to herpes simplex virus type 2 (HSV-2) infection. HSV hepatitis is a rare but serious complication in liver transplantation. Acyclovir-resistant HSV strains may emerge in immunocompromised patients. Following intraperitoneal inoculation, HSV-2 induces necrotizing hepatitis in mice. We studied the virus spread and mortality following intraperitoneal inoculation of HSV-2 RK (an acyclovir-resistant recombinant virus with altered thymidine kinase activity) as compared to its parent virus 8620K. Neither the 50% lethal dose (LD50) nor the average survival time was significantly different between the two strains. Parenteral acyclovir treatment was found to be effective against 8620K but not RK infection. Parenteral foscarnet treatment was effective against both RK and 8620K, and also inhibited the spread of either virus to the liver, spinal cord and brain. Peroral foscarnet administration was found to prevent the virus growth in the liver.
D000212:Acyclovir / Q000494:pharmacology; D000818:Animals; D001087:Arabinonucleosides / Q000494:pharmacology; D001921:Brain / Q000821:virology; D002522:Chlorocebus aethiops; D004352:Drug Resistance, Microbial; D017245:Foscarnet / Q000494:pharmacology*; D006524:Hepatitis, Viral, Animal / Q000188:drug therapy* / Q000821:virology; D006558:Herpes Genitalis / Q000188:drug therapy*; D018258:Herpesvirus 2, Human / Q000187:drug effects*; D006801:Humans; D007274:Injections, Intraperitoneal; D007928:Lethal Dose 50; D051379:Mice; D008809:Mice, Inbred C3H; D010746:Phosphonoacetic Acid / Q000494:pharmacology; D013936:Thymidine / Q000031:analogs & derivatives / Q000494:pharmacology; D014709:Vero Cells; D014740:Vidarabine / Q000494:pharmacology
D001087:Arabinonucleosides; D017245:Foscarnet; D014740:Vidarabine; D010746:Phosphonoacetic Acid; C010032:thymine arabinoside; D013936:Thymidine; D000212:Acyclovir