Role of the Serine-Threonine Kinase PAK-1 in Myxoma Virus Replication

Current Status for High Titre Poxvirus Stock Preparation in CEF Under Serum-Free Medium Conditions: Implication for Vaccine Development

“…We constructed an ALVAC-YFP vector that expresses the enhanced yellow fluorescent protein (EYFP) under the control of a vaccinia virus synthetic early/late promoter (VVsynE/L). The rabbit leporipoxvirus myxoma-GFP expresses the enhanced green fluorescent protein (EGFP) under the control of the VVsynE/L promoter as previously described (Opgenorth et al 1992;Johnston et al 2003). The vaccinia virus VV-65 expresses b-galactosidase under the vaccinia early/late promoter p7.5 as previously described (Chakrabarti et al 1997).…”

The role of CCR5 in vaccinia virus pathogenesis

“…Grb2 participates in the Ras signaling cascade, associating with the guanine nucleotide exchange factor Sos, and thus may link signaling effectors to the MAP kinase pathway. This activation of the MAPK pathway appears to be virus-specific, since U0126, a MAPK/Erk1,2 inhibitor, has been shown to attenuate VACV infection, but increase myxoma virus replication in permissive 3T3 cell lines (314). It has also been demonstrated that HGF/c-Met engagement triggers ERK activation (324,325).…”

“…In recent years accumulating evidence suggests that poxviral replication requires the manipulation of target cells in the context of activation of signaling pathways (314,416). In chapter 2 we provide evidence for VACV activation of the chemokine receptor, CCR5, and the phosphorylation-activation of a number of signaling effectors.…”

“…In a subsequent publication, Johnston et. al identified a role for the serine-threonine kinase, PAK-1, in myxoma virus replication, and suggested that the permissiveness of target cells to infection resides in their ability to activate this kinase (314 Although VACV infects a variety of cells, some poxviruses fail to grow in certain host cells in vitro, a phenomenon known as host restriction (173,174,192,215,286,288,421,670,763). In these restrictive cells, poxviruses enter the cell efficiently but fail to replicate.…”

“…The involvement of chemokine receptors in poxviral infection was suggested in studies utilizing the rabbit poxvirus, myxoma. Specifically, CCR5 was implicated in mediating cell target susceptibility to infection in BGMK cells (355), later shown to correlate with intracellular signaling (314,416). In a recent publication we provided evidence that virus activation of CCR5 leads to the selective activation of distinct signaling pathways that are advantageous for the virus (536).…”