GENERALIZED CYTOMEGALOVIRUS (CMV) INFECTION AND CMV-INDUCED PNEUMONITIS IN THE RAT - COMBINED EFFECT OF 9-(1,3-DIHYDROXY-2-PROPOXYMETHYL) GUANINE AND SPECIFIC ANTIBODY TREATMENT

The combined effect of 9-(1,3-dihydroxy-2-propoxymethyl)guanine (DHPG, ganciclovir) and hyper immune serum (HIS) was studied in two differen t-rat models. In the first model, a lethal generalized rat cytomegalov irus (RCMV) infection was established in immunosuppressed Brown Norway (BN) rats. Treatment with DHPG or hyper immune serum (HIS) effectivel y reduced both mortality rate and virus titers in the liver and lungs. By-combined treatment the effective dose of both DHPG and HIS was red uced to 25%. The fractionary effective dose was 0.5 indicating a moder ate synergistic effect on survival. Combined treatment also establishe d a significant reduction of virus titers in lungs and liver (P < 0.01 ), but not in spleen. In the second model, interstitial pneumonia (IP) was established in RCMV-infected immunosuppressed BN rats after allog eneic bone marrow transplantation. IP was characterized by infiltratio n of mononuclear eels and diffuse thickening of the alveolar septal wa ll. DHPG reduced virus titers in the lungs but had no effect on IP. In contrast, HIS significantly reduced both virus titers and histopathol ogic changes in the lungs. Combined DHPG and HIS treatment minimized v irus titers in internal organs and CMV-induced IP. Likewise, combined DHPG and control immune serum treatment significantly reduced immunopa thologic changes in the lungs.