Biology Reference
In-Depth Information
ISGF3 and subsequent ISG induction (Paulus et al. 2006). In MCMV, the M27
protein blocks both type I and type II IFN signaling by binding and degrading
STAT2, a protein that, until this study, was not believed to be involved in IFNγ-
dependent responses (Zimmermann et al. 2005). The importance of this pheno-
type is illustrated by the indispensability of M27 for MCMV growth in vivo
(Abenes et al. 2001; Zimmermann et al. 2005). Interestingly, both HCMV and
MCMV have been shown to target STAT2 albeit via different mechanisms.
CMV Interference with ISG Function
The antiviral effects of the IFN response are ultimately the result of IFN- or IRF3-
induced host cell proteins. Protein synthesis is shut off during viral infection by
protein kinase R (PKR) and 2′-5′ oligoadenylate synthetase (OAS)/RNaseL
(reviewed in Schneider and Mohr 2003). OAS and PKR are induced by type I and
type II IFNs and the proteins are activated following exposure to viral dsRNA.
Vaccinia virus (VV) prevents activation of PKR and OAS and VV lacking this
function could be complemented by infection with live, but not UV-inactivated
HCMV (Child et al. 2002). Subsequent work identified the HCMV proteins
pTRS1 and pIRS1 to block OAS-mediated eIF2α phosphorylation and to reduce
RNA degradation by RNase L (Child et al. 2004).
Interference with Antigen Presentation by Cytomegalovirus
Among the best studied immune modulators of CMVs are viral inhibitors of
antigen presentation (VIPRs) (Johnson and Hegde 2002; Reddehase 2002;
Yewdell and Hill 2002; Basta and Bennink 2003; Mocarski 2004; Reddehase
et al. 2004; Pinto and Hill 2005). While nonessential in vitro, VIPRs might
enable CMV to establish chronic infection despite a tremendous cellular
immune response. The presence of multiple genes and mechanisms in all CMV
species indicates that inhibiting antigen presentation is critical to the success of
the virus. CMV affects both antigen presentation by major histocompatibility
complex class I (MHC-I) and class II (MHC-II). Since modulation of MHC-II
has been recently reviewed (Wiertz et al. 2007), we will focus on new findings
on MHC-I downregulation.
Inhibition of Antigen Presentation to CD8
+
T Lymphocytes
CD8
+
T cells defend the host against viruses. They are able to kill infected cells upon
recognizing virus-derived peptides displayed by MHC-I molecules at the cell surface.
