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Backes, S.* ; Sperling, K.M.* ; Zwilling, J.* ; Gasteiger, G.* ; Ludwig, H.* ; Kremmer, E. ; Schwantes, A.* ; Staib, C.* ; Sutter, G.*

Viral host-range factor C7 or K1 is essential for modified vaccinia virus Ankara late gene expression in human and murine cells, irrespective of their capacity to inhibit protein kinase R-mediated phosphorylation of eukaryotic translation initiation factor 2α.

J. Gen. Virol. 91, 470-482 (2010)
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Vaccinia virus (VACV) infection induces phosphorylation of eukaryotic translation initiation factor 2{alpha} (eIF2{alpha}), which inhibits cellular and viral protein synthesis. In turn, VACV evolved the capacity to antagonise this anti-viral response by expressing the viral host range proteins K3 and E3. Here, we reveal that the host range genes K1L and C7L also prevent eIF2{alpha} phosphorylation in modified VACV Ankara (MVA) infection of several human and murine cell lines. Moreover, C7L-deleted MVA (MVA-{Delta}C7L) lacked late gene expression, which could be rescued by the function of either host range factor K1 or C7. We demonstrate that viral gene expression was blocked after viral DNA replication, and that it was independent of apoptosis induction. Furthermore, we found that eIF2{alpha} phosphorylation in MVA-{Delta}C7L infected cells is mediated by protein kinase R (PKR) as shown in murine embryonic fibroblasts (MEF) lacking PKR function, and demonstrated that this is not due to reduced E3L gene expression. The block of eIF2{alpha} phosphorylation by C7 could be complemented by K1 in cells infected with MVA-{Delta}C7L encoding a re-inserted K1L gene (MVA-{Delta}C7L-K1L). Importantly, our data illustrate that eIF2{alpha} phosphorylation by PKR is not responsible for the block of late viral gene expression. This suggests that other mechanisms targeted by C7 and K1 are essential for completing the MVA gene expression cycle and likely also for VACV replication in a diverse set of cell types.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter C7L; K1L; modified vaccinia virus Ankara; PKR; elF2alpha
ISSN (print) / ISBN 0022-1317
e-ISSN 1465-2099
Quellenangaben Band: 91, Heft: 2, Seiten: 470-482 Artikelnummer: , Supplement: ,
Verlag Society for General Microbiology
Begutachtungsstatus Peer reviewed