Table 1.
In vivo and in vitro proteins substrates of the ORF66/US3 kinases
| Alphaherpesvirus | ORF66/US3 phosphorylated protein substrate |
In vivo/ in vitro target? |
Function |
|---|---|---|---|
| VZV (Eisfeld et al. 2006; Erazo et al. 2008; Kinchington et al. 2000; Kinchington and Turse 1998) | IE62 (ICP4) | +/+ | IE62 cytoplasmic accumulation/IE62 tegument inclusion |
| VZV, HSV, PRV | Matrin 3 | +/ND | ? |
| VZV (Walters et al. 2009), HSV-1 (Poon and Roizman 2007) | HDAC 1 and 2 | +/ND | Block HDAC transcriptional repression |
| HSV-1 (Kato et al. 2009; Wisner et al. 2009) | γB | +/+ | Downregulate γB surface expression, promote virion nuclear egress |
| HSV-1 (Kato et al. 2005; Mou et al. 2009) | UL31 | +/+ | Promote virion nuclear egress |
| HSV-1 (Kato et al. 2005; Purves et al. 1991; Ryckman and Roller 2004) | UL34 | +/+ | ? |
| HSV-1 (Mou et al. 2007) | Lamin A/C | +/+ | Disrupt nuclear lamina, promote virion nuclear egress |
| HSV-1 (Leach et al. 2007) | Emerin | +/ND | Disrupt nuclear lamina, promote virion nuclear egress |
| HSV1,2 (Daikoku et al. 1994; Kato et al. 2005) | US9 | +?/+ | ? |
| HSV-1 (Kato et al. 2005; Purves et al. 1993; Smith-Donald and Roizman 2008) | ICP22 | +?/+ | ? |
| HSV-2 (Daikoku et al. 1995) | UL12 | ND/+ | ? |
| HSV-2 (Murata et al. 2002) | Cytokeratin 17 | +?/+ | Cell morphological changes |
| HSV-1 (Cartier et al. 2003b; Kato et al. 2005) | Bad | +/+ | Block apoptosis |
| HSV-1 (Cartier et al. 2003a; Kato et al. 2005) | Bid | ND/+/− | Block apoptosis, mediate protection from granzyme B cleavage of Bid |
| HSV-1 (Liang and Roizman 2008) | IFNRa | +/ND | Inhibit activation of IFN-γ genes |
| HSV-1 (Benetti and Roizman 2004) | PKA | +/ND | PKA activation |
| PRV (Van den Broeke et al. 2009b) | PAK1 and PAK2 | +/+ | Actin projection formation and stress fiber dissasembly |
| HSV-1 (Benetti and Roizman 2007) | Procaspase 3 | ND/+ | Block activation of procaspase 3 and apoptosis |
| HSV-1 (Smith-Donald and Roizman 2008) | cdc25C Phosphatase | ND/+ | Enhance interaction with ICP22, optimize viral gene expression |
Specific US3 kinase and its protein target are noted. Evidence of US3 induced phosphorylation in vivo or in vitro is denoted by a plus (+) sign or not determined (ND). Functions associated with phosphorylation of each protein are also listed