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

Abstract

The combined effect of 9-(1,3-dihydroxy-2-propoxymethyl)guanine (DHPG, ganciclovir) and hyper immune serum (HIS) was studied in two different rat models. In the first model, a lethal generalized rat cytomegalovirus (RCMV) infection was established in immunosuppressed Brown Norway (BN) rats. Treatment with DHPG or hyper immune serum (HIS) effectively reduced both mortality rate and virus titers in the liver and lungs. By combined treatment the effective dose of both DHPG and HIS was reduced to 25%. The fractionary effective dose was 0.5, indicating a moderate synergistic effect on survival. Combined treatment also established 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 allogeneic bone marrow transplantation. IP was characterized by infiltration of mononuclear cells and diffuse thickening of the alveolar septal wall. DHPG reduced virus titers in the lungs but had no effect on IP. In contrast, HIS significantly reduced both virus titers and histopathologic changes in the lungs. Combined DHPG and HIS treatment minimized virus titers in internal organs and CMV-induced IP. Likewise, combined DHPG and control immune serum treatment significantly reduced immunopathologic changes in the lungs.