| First Author | Tufariello JM | Year | 1994 |
| Journal | Proc Natl Acad Sci U S A | Volume | 91 |
| Issue | 23 | Pages | 10987-91 |
| PubMed ID | 7971996 | Mgi Jnum | J:21532 |
| Mgi Id | MGI:69499 | Doi | 10.1073/pnas.91.23.10987 |
| Citation | Tufariello JM, et al. (1994) Adenovirus E3 14.7-kilodalton protein, an antagonist of tumor necrosis factor cytolysis, increases the virulence of vaccinia virus in severe combined immunodeficient mice. Proc Natl Acad Sci U S A 91(23):10987-91 |
| abstractText | The adenovirus (Ad) 14.7-kDa protein, which is called 14.7K, has been shown to function as a general inhibitor of tumor necrosis factor alpha (TNF) cytolysis in tissue culture assays, and the effect of this antagonism on viral pathogenesis in vivo has recently been explored. In infections of immunocompetent BALB/c mice, we have shown previously that Ad type 2 (Ad2) 14.7K, when cloned into a vaccinia virus (VV) vector in combination with the gene for murine TNF, is able to counteract much of the attenuating effect of TNF on VV virulence. In the present study we utilized VV constructs expressing various combinations of Ad 14.7K and TNF in infections of T- and B-cell-deficient C.B-17 severe combined immunodeficient (SCID) mice to determine whether these cells are directly necessary for 14.7K's reversal of TNF-mediated viral attenuation. The mice were infected by the intranasal route, and mortality, morbidity, histopathology, and virus replication in selected organs were evaluated at various times after infection. We found that, in the SCID murine pneumonia model, neither the attenuation by TNF nor its reversal by Ad 14.7K require the participation of T or B lymphocytes or their secreted products. SCID mice infected with VV expressing both 14.7K and TNF [VV 14.7(+)/TNF] were generally well clinically for the first 7-10 days after infection; however, they developed a subacute or chronic illness, succumbing to diseminated VV infection at least 3 weeks earlier than mice infected with VV expressing TNF alone [VV 14.7(-)/TNF]. Animals infected with VV 14.7(+)/TNF were shown to have higher initial titers of virus and delayed clearance from the lungs as well as more rapid spread of virus to internal organs than animals infected with VV 14.7(-)/TNF. SCID mice infected intranasally with VV without TNF showed a dramatic increase in acute disease and succumbed within the first 1-2 weeks after infection, independent of Ad 14.7K expression. |
