How Parvoviruses Escape Interferon Control

MVM 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.

 

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