CYTOMEGALOVIRUS-INFECTION ENHANCES SMOOTH-MUSCLE CELL-PROLIFERATION AND INTIMAL THICKENING OF RAT AORTIC ALLOGRAFTS

Inbred DA (AG-B4, RT1(a)) and WF (AG-B2, RT1(v)) rats were used as don ors and recipients of aortic allografts. The recipient rats were inocu lated i.p. either on day 1 (early infection) or on day 60 (late infect ion) with 10(5) plaque-forming units of rat cytomegalovirus (RCMV). Th e control rats were left noninfected. The presence of viral infection was demonstrated by plaque assays from biopsies of the salivary glands , liver, and spleen at sacrifice. The rats received 300 muCi [H-3] thy midine by i.v. injection 3 h before sacrifice, and the grafts were rem oved at various time points for histology, immunohistochemistry, and a utoradiography. RCMV infection significantly enhanced the generation o f allograft arteriosclerosis. Infection at the time of transplantation had two important effects. First, the infection was associated with a n early, prominent inflammatory episode and proliferation of inflammat ory cells in the allograft adventitia. Second, the viral infection dou bled the proliferation rate of smooth muscle cells and the arterioscle rotic alterations in the intima. In late infection the impact of RCMV infection on the allograft histology was nearly nonexistent. RCMV infe ction showed no effect in syngeneic grafts. These results suggest that early infection is more important to the generation of accelerated al lograft arteriosclerosis than late infection, and that an acute alloim mune response must be associated with virus infection, to induce accel erated allograft arteriosclerosis. RCMV-infected aortic allografts, as described here, provide the first experimental model to investigate t he interaction between the virus and the vascular wall of the transpla nt.