20962097
not annotated - annotated - LINNAEUS only
Variola and monkeypox viruses utilize conserved mechanisms of virion motility and release that depend on abl and SRC family tyrosine kinases.
Vaccinia virus (VacV) enters mammalian cells, replicates extranuclearly, and produces virions that move to the cell surface along microtubules, fuse with the plasma membrane, and move from infected cells toward apposing cells on actin-filled membranous protrusions or actin tails. To form actin tails, cell-associated enveloped virions (CEV) require Abl and Src family tyrosine kinases. Furthermore, release of CEV from the cell requires Abl but not Src family tyrosine kinases and is blocked by imatinib mesylate (STI-571; Gleevec), an Abl family kinase inhibitor used to treat chronic myelogenous leukemia in humans. Here we demonstrate that the Poxviridae family members monkeypox virus (MPX) and variola virus (VarV) use conserved mechanisms for actin motility and extracellular enveloped virion (EEV) release. Furthermore, we show that imatinib mesylate is effective in a mouse model of infection with VacV, whether delivered prophylactically or postinfection, and restricts spread of virions from the site of inoculation. While inhibitors of both Src and Abl family kinases, such as dasatinib (BMS-354825; Sprycel), are effective in limiting dissemination of VacV, VarV, and MPX in vitro, members of this class of drugs appear to have immunosuppressive effects in vivo that preclude their use as anti-infectives. Together, these data suggest a possible utility for imatinib mesylate in treating smallpox or MPX infections or complications associated with vaccination.
Ann file
T1 Species 0 7;22 29 Variola viruses
N1 Reference T1 Taxonomy:10255
T2 Species 12 29 monkeypox viruses
N2 Reference T2 Taxonomy:10244
T3 Species 144 158 Vaccinia virus
N3 Reference T3 Taxonomy:10245
T4 Species 160 164 VacV
N4 Reference T4 Taxonomy:10245
T5 Species 755 761 humans
N5 Reference T5 Taxonomy:9606
T6 Species 818 833 monkeypox virus
N6 Reference T6 Taxonomy:10244
T7 Species 835 838 MPX
N7 Reference T7 Taxonomy:10244
T8 Species 844 857 variola virus
N8 Reference T8 Taxonomy:10255
T9 Species 859 863 VarV
N9 Reference T9 Taxonomy:10255
T10 Species 1021 1026 mouse
N10 Reference T10 Taxonomy:10090
T11 Species 1051 1055 VacV
N11 Reference T11 Taxonomy:10245
T12 Species 1309 1313 VacV
N12 Reference T12 Taxonomy:10245
T13 Species 1315 1319 VarV
N13 Reference T13 Taxonomy:10255
T14 Species 1325 1328 MPX
N14 Reference T14 Taxonomy:10244
T15 Species 1557 1560 MPX
N15 Reference T15 Taxonomy:10244