20943971
not annotated - annotated - LINNAEUS only
Roles of vaccinia virus genes E3L and K3L and host genes PKR and RNase L during intratracheal infection of C57BL/6 mice.
The importance of the 2'-5' oligoadenylate synthetase (OAS)/RNase L and double-stranded RNA (dsRNA)-dependent protein kinase (PKR) pathways in host interferon induction resulting from virus infection in response to dsRNA has been well documented. In poxvirus infections, the interactions between the vaccinia virus (VV) genes E3L and K3L, which target RNase L and PKR, respectively, serve to prevent the induction of the dsRNA-dependent induced interferon response in cell culture. To determine the importance of these host genes in controlling VV infections, mouse single-gene knockouts of RNase L and PKR and double-knockout mice were studied following intratracheal infection with VV, VVDeltaK3L, or VVDeltaE3L. VV caused lethal disease in all mouse strains. The single-knockout animals were more susceptible than wild-type animals, while the RNase L(-/-) PKR(-/-) mice were the most susceptible. VVDeltaE3L infections of wild-type mice were asymptomatic, demonstrating that E3L plays a critical role in controlling the host immune response. RNase L(-/-) mice showed no disease, whereas 20% of the PKR(-/-) mice succumbed at a dose of 10(8) PFU. Lethal disease was routinely observed in RNase L(-/-) PKR(-/-) mice inoculated with 10(8) PFU of VVDeltaE3L, with a distinct pathology. VVDeltaK3L infections exhibited no differences in virulence among any of the mouse constructs, suggesting that PKR is not the exclusive target of K3L. Surprisingly, VVDeltaK3L did not disseminate to other tissues from the lung. Hence, the cause of death in this model is respiratory disease. These results also suggest that an unanticipated role of the K3L gene is to facilitate virus dissemination.
Ann file
T1 Species 9 23 vaccinia virus
N1 Reference T1 Taxonomy:10245
T2 Species 115 119 mice
N2 Reference T2 Taxonomy:10090
T3 Species 423 437 vaccinia virus
N3 Reference T3 Taxonomy:10245
T4 Species 439 441 VV
N4 Reference T4 Taxonomy:10245
T5 Species 668 670 VV
N5 Reference T5 Taxonomy:10245
T6 Species 683 688 mouse
N6 Reference T6 Taxonomy:10090
T7 Species 750 754 mice
N7 Reference T7 Taxonomy:10090
T8 Species 807 809 VV
N8 Reference T8 Taxonomy:10245
T9 Out-of-scope 811 813 VV
N9 Reference T9 Taxonomy:10245
T10 Species 870 875 mouse
N10 Reference T10 Taxonomy:10090
T11 Species 991 995 mice
N11 Reference T11 Taxonomy:10090
T12 Species 1058 1062 mice
N12 Reference T12 Taxonomy:10090
T13 Species 1181 1185 mice
N13 Reference T13 Taxonomy:10090
T14 Species 1233 1237 mice
N14 Reference T14 Taxonomy:10090
T15 Species 1335 1339 mice
N15 Reference T15 Taxonomy:10090
T16 Species 1485 1490 mouse
N16 Reference T16 Taxonomy:10090
#1 AnnotatorNotes T9 TODO check
T17 Species 838 840 VV
N17 Reference T17 Taxonomy:10245