Overview of the role of vGPRs in a viral setting
| vGPCR (Virus and Lytic Expression Kinetics) | Role in Lytic Infection | Role in Latent Infection | Role in Dissemination/Immune Evasion | Orthologs |
|---|---|---|---|---|
| UL33 (HCMV late) (Davis-Poynter et al., 1997) | Dispensable (Margulies et al., 1996) but enhances spread in multistep growth analyses (van Senten et al., 2020a); constitutive signaling (Casarosa et al., 2003a) | Expression detected but no role established (Cheng et al., 2017) | Murine and rat models suggest roles in replication in salivary gland, latency, and dendritic cell trafficking (Frank et al., 2019) | Murine - M33 rat - R33 |
| UL78 (HCMV early) (Wagner et al., 2012) | Dispensable (Michel et al., 2005) but important for entry into epithelial cells and replication in epi/endothelial cells (O’Connor and Shenk, 2012) | Expression detected but no role established (Cheng et al., 2017) | Murine and rat models suggest importance in replication in specific cell types in vivo (Oliveira and Shenk, 2001; Kaptein et al., 2003) | Murine - M78 rat - R78 |
| US27 (HCMV late) (Vieira et al., 1998; Chambers et al., 1999; Margulies and Gibson, 2007) | Important for extracellular spread (O’Connor and Shenk, 2011); promotion of cell growth and survival (Tu and Spencer, 2014) | Expression not detected (Cheng et al., 2017; Shnayder et al., 2018) | Highly conserved but in vivo role unclear (Stegman and Margulies, 2017; Frank et al., 2019) | Present in primate CMVs but not rodent CMVs (Alcendor et al., 2009) |
| US28 (HCMV early) (Vieira et al., 1998) | Dispensable (Vieira et al., 1998; Humby and O’Connor, 2015); enhances infection of epithelial cells and smooth muscle cells (Noriega et al., 2014; Lollinga et al., 2017); constitutive and ligand-induced signaling (Krishna et al., 2018) | Required for latency in in vitro models (Humby and O’Connor, 2015; Krishna et al., 2017a; Zhu et al., 2018); required for reactivation in humanized mice (Crawford et al., 2019) | Induces cell migration and adhesion (Melnychuk et al., 2004; Vomaske et al., 2009; Hjorto et al., 2013; Wu and Miller, 2016; Farrell et al., 2018; Aslam et al., 2019); chemokine sink (Randolph-Habecker et al., 2002); myeloid differentiation (Zhu et al., 2018; Crawford et al., 2019) | Present in primate CMVs but not rodent CMVs (Alcendor et al., 2009); five rhesus CMV US28 homologs characterized |
| U12 (HHV-6A/B late) (Isegawa et al., 1998) | Ligand-induced signaling (Isegawa et al., 1998); likely dispensable for viral replication (Dominguez et al., 1999) | Unknown | Unknown | Homologs not functionally characterized |
| U51 (HHV-6A/B early) (Menotti et al., 1999) | Enhances viral replication (Zhen et al., 2005) | Unknown | Leukocyte migration/immunomodulation (Catusse et al., 2008) | Homologs not functionally characterized |
| U12 (HHV-7) | Ligand-induced signaling (Nakano et al., 2003; Tadagaki et al., 2005) | Unknown | Unknown | Homologs not functionally characterized |
| U51 (HHV-7) | Ligand-induced signaling (Tadagaki et al., 2005) | Unknown | Unknown | Homologs not functionally characterized |
| BILF1 (EBV early) | Immune evasion (cell intrinsic and extrinsic) (Arfelt et al., 2015; Morales-Sánchez and Fuentes-Panana, 2018) not required for lytic replication (Zuo et al., 2011) | Expressed at low levels (Tierney et al., 2015) | Likely immune evasion including evasion of cytotoxic T-cell recognition | BILF1 homologs characterized in primate lymphocryptoviruses (Spiess et al., 2015a) |
| ORF74 (KSHV early) (Chiou et al., 2002) | Necessary for efficient lytic replication (Sandford et al., 2009) | Expression kept at low levels (Vischer et al., 2014); possible reactivation from latency (Chen et al., 2009; Sandford et al., 2009) | Murine models indicate important roles in reactivation from latency (Moorman et al., 2003; López-Rodríguez et al., 2019) | MHV68 ORF74 (Virgin et al., 1997) |