Most cell types in mammalian hosts detect virus infection via pattern recognition receptors (PRRs), which sense the nucleic acid products of virus replication. The RIG-I-like receptors (RLRs), RIG-I (retinoic acid inducible gene-I) and MDA5 (melanoma differentiation-associated gene 5), are involved in sensing cytosolic RNA species, and activation via the adapter molecule MAVS leads to the production of type I IFNs, via IRF3, and of pro-inflammatory cytokines, via NF-κB.
This paper examines the role of MAVS, which is involved in the detection of RNA Pol III-synthesized RNA intermediates in response to dsDNA viruses. The results suggest that the Minute virus of mice parvovirus (MVM) efficiently evades antiviral immune mechanisms imposed by type I IFNs. Clever virus – small, but perfectly formed.
Parvovirus evades interferon-dependent viral control in primary mouse embryonic fibroblasts. Virology. 2013 May 12. pii: S0042-6822(13)00173-6. doi: 10.1016/j.virol.2013.03.020
Engagement of innate viral sensors elicits a robust antiviral program via the induction of type I interferons (IFNs). Innate defense mechanisms against ssDNA viruses are not well defined. Here, we examine type I IFN induction and effectiveness in controlling a ssDNA virus. Using mouse embryonic fibroblasts (MEFs), we found that a murine parvovirus, minute virus of mice (MVMp), induced a delayed but significant IFN response. MEFs deficient in mitochondrial antiviral signaling protein (MAVS) mounted a wild-type IFN response to MVMp infection, indicating that RIG-I-dependent RNA intermediate recognition is not required for innate sensing of this virus. However, MVMp-induced IFNs, as well recombinant type I IFNs, were unable to inhibit viral replication. Finally, MVMp infected cells became unresponsive to Poly (I:C) stimulation. Together, these data suggest that the MVMp efficiently evades antiviral immune mechanisms imposed by type I IFNs, which may in part explain their efficient transmission between mice.