ACUTE, LETHAL, NATURAL-KILLER CELL-RESISTANT MYELOPROLIFERATIVE DISEASE INDUCED BY POLYOMAVIRUS IN SEVERE COMBINED IMMUNODEFICIENT MICE

Infection of severe combined immunodeficient mice, which lack T and B lymphocytes, with polyomavirus (PyV) induced an acute hematological di sorder lending to the death of the mice by 2 weeks postinfection The d isease was characterized by a dramatic decrease in megakaryocytes, mul tiple hemorrhages, anemia, thrombocytopenia, splenomegaly, a massive m yeloproliferation and splenic erythroproliferation with a defect in ma turation of the myeloid elements similar to that in acute leukemia. Th is pathology in severe combined immunodeficient mice is very different from that of the well-characterized tumor profiles induced by PyV in normal newborn or nude mice. Viral T and capsid (VP1) antigens and vir al genome were detected in some cells in the spleen, but not in the ma jority of the proliferating myeloid cells. This suggests that the myel oproliferation is induced by some indirect mechanism, such as secretio n of growth factors or cytokines by virus-infected cells, rather than by direct transformation by PyV. Neither the spread of PyV, its replic ation in different organs, nor the pathogenesis or the time of death w ere altered by depleting natural killer cells in vivo by anti-natural killer fell antibodies. Analysis of the spleen leukocyte population in dicated that the cells expressed high levels of class I major histocom patibility complex antigens and were resistant to lysis by activated n atural killer cells.