A MODEL FOR MIXED VIRUS-DISEASE - COINFECTION WITH MOLONEY MURINE LEUKEMIA-VIRUS POTENTIATES RUNTING INDUCED BY POLYOMAVIRUS (A2 STRAIN) INBALB C AND NIH SWISS MICE/

Polyomavirus was originally isolated by Ludwick Gross from a mixture t hat also contained a murine retrovirus. A possible pathogenic interact ion between polyomavirus and an endogenous mouse retrovirus locus (mtv -7) in polyomavirus-induced cancer has also been reported. To study po tential interactive effects of polyomavirus (Py) and Moloney murine le ukemia retrovirus (M-MuLV), newborn Balb/c and NIH Swiss mice were inf ected with high titer wild-type Py (A2 strain) and M-MuLV. Dramaticall y stunted growth (runting) occurred in 100% of the doubly inoculated m ice, while much lower frequency of runting occurred in animals infecte d with Py alone and not at all with M-MuLV-infected mice. in situ hybr idization for Py DNA showed ongoing Py replication and inflammation in kidneys (atypical of most mice singly infected by Py) of runted doubl y inoculated mice. In addition, high Py viral replication continued we ll past the usual acute stage termination. M-MuLV replication was also initially inhibited in bone marrow by simultaneous Py infection. No M -MuLV replication was seen in singly or doubly infected mouse kidneys. Runting was very rapid, observable within 2 days after co-infection, arguing against an adaptive or antigen-specific immunological mechanis m. One possibility was that a cytokine-driven acute response mechanism was involved. Supporting this view, RNAse protection assays for vario us cytokine RNAs showed that several were specifically elevated in kid neys of doubly infected mice. Three patterns were observed: (1) IL-6 w as elevated in doubly infected mice early after infection (7 days), bu t it declined at later times (19 days); (2) IFN-gamma, IL-1 beta, and IL-10 were elevated at both early and late times; and (3) TNF-alpha, I L-12p40, and possibly TNF-beta were elevated only at late times. While the cytokines in the third category might be indicative of infiltrati ng inflammatory cells, it seems possible that cytokines in the first o r second categories might be involved in establishing runting and ongo ing polyoma DNA replication in the doubly infected mice. (C) 1995 Acad emic Press, Inc.