A RAT CYTOMEGALOVIRUS-INFECTION MODEL AS A TOOL FOR IMMUNOTOXICITY TESTING

A rat cytomegalovirus infection model for use in immunotoxicity testin g has been developed. In resistance against viruses, natural killer ce lls and cytotoxic T-cells play an important role. Therefore, this mode l complements other rat host resistance models for immunotoxicity test ing, i.e. existing bacterial and parasitic infection models in which c ytotoxic T-cells and natural killer cells play a minor role. Host resi stance against cytomegalovirus infections in the rat was determined by titrating infectious virus levels in organs after cytomegalovirus inf ection in an in vitro infectivity test denoted as the Plaque Forming U nit (PFU) Test, In this test, homogenates of different organs were inv estigated for infectious virus titers on rat embryonic cell monolayers . We demonstrated that in the salivary gland, the major target organ f or rat cytomegalovirus, virus was detectable from 8 days onward after intraperitoneal infection. To show that this model is suitable for the detection of immunotoxicity four different methods for immunosuppress ion were investigated: 1. gamma-irradiation, 2. congenitally athymic r ats, 3. chemically induced immunosuppression, 4. ultraviolet-B (UVB) i rradiation. Rat cytomegalovirus titers in the salivary glands of irrad iated (500 rad 1 day prior to infection) or congenitally athymic rats were significantly increased as compared to non-irradiated rats and eu thymic control rats respectively. In TOX-Wistar rats, given 20 or 80 m g bis(tri-n-butyltin)oxide (TBTO) per kg food beginning 6 weeks before cytomegalovirus infection, a regimen known to have immunotoxic effect s, cytomegalovirus titers in the salivary glands were significantly in creased as compared to non-TBTO-treated cytomegalovirus infected rats. Exposure to a suberythemal doses of UVB, which is known to induce imm unotoxic effects, induced a significant increase in cytomegalovirus ti ters in the salivary gland as compared to non-UVB-exposed rats. Theref ore it is concluded that this infection model is suitable for the asse ssment of immunotoxic effects induced by environmental components.