A rat cytomegalovirus infection model as a tool for immunotoxicity testing.
A rat cytomegalovirus infection model for use in immunotoxicity testing has been developed. In resistance against viruses, natural killer cells and cytotoxic T-cells play an important role. Therefore, this model complements other rat host resistance models for immunotoxicity testing, i.e. existing bacterial and parasitic infection models in which cytotoxic T-cells and natural killer cells play a minor role. Host resistance against cytomegalovirus infections in the rat was determined by titrating infectious virus levels in organs after cytomegalovirus infection in an in vitro infectivity test denoted as the Plaque Forming Unit (PFU) Test. In this test, homogenates of different organs were investigated for infectious virus titers on rat embryonic cell monolayers. We demonstrated that in the salivary gland, the major target organ for 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 immunosuppression were investigated: 1. gamma-irradiation, 2. congenitally athymic rats, 3. chemically induced immunosuppression, 4. ultraviolet-B (UVB) irradiation. Rat cytomegalovirus titers in the salivary glands of irradiated (500 rad 1 day prior to infection) or congenitally athymic rats were significantly increased as compared to non-irradiated rats and euthymic control rats respectively. In TOX-Wistar rats, given 20 or 80 mg bis(tri-n-butyltin)oxide (TBTO) per kg food beginning 6 weeks before cytomegalovirus infection, a regimen known to have immunotoxic effects, cytomegalovirus titers in the salivary glands were significantly increased as compared to non-TBTO-treated cytomegalovirus infected rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Garssen
J
J
National Institute of Public Health and Environmental Protection, Bilthoven, Netherlands.
Van der Vliet
H
H
De Klerk
A
A
Goettsch
W
W
Dormans
J A
JA
Bruggeman
C A
CA
Osterhaus
A D
AD
Van Loveren
H
H
D000818:Animals; D002478:Cells, Cultured; D003586:Cytomegalovirus Infections / Q000276:immunology* / Q000821:virology; D005347:Fibroblasts; D005720:Gamma Rays; D007111:Immunity, Cellular / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000633:toxicity; D008297:Male; D018448:Models, Immunological; D051381:Rats; D011919:Rats, Inbred Strains; D017208:Rats, Wistar; D013950:Thymus Gland / Q000002:abnormalities; D016707:Tissue Fixation; D014220:Trialkyltin Compounds / Q000633:toxicity; D014466:Ultraviolet Rays; D010948:Viral Plaque Assay
D007166:Immunosuppressive Agents; D014220:Trialkyltin Compounds; C005961:bis(tri-n-butyltin)oxide