Cell-Type-Specific Activation of the Oligoadenylate Synthetase–RNase L Pathway by a Murine Coronavirus

• DOI: 10.1128/jvi.00769-13
• Publication Date: 2013-05-23T03:51:28Z
• Authors: Ling Zhao; L. Dillon Birdwell; Ashley Wu; Ruth Elliott; Kristine M. Rose; Judith M. Phillips; Yize Li; Judith Grinspan; Robert H. Silverman; Susan R. Weiss
• Keywords: Mouse hepatitis virus

Previous studies have demonstrated that the murine coronavirus mouse hepatitis virus (MHV) nonstructural protein 2 (ns2) is a 2',5'-phosphodiesterase inhibits activation of interferon-induced oligoadenylate synthetase (OAS)-RNase L pathway. Enzymatically active ns2 required for efficient MHV replication in macrophages, as well induction C57BL/6 mice. In contrast, following intranasal or intracranial inoculation, brain not dependent on an enzymatically ns2. The wild-type strain A59 (A59) and mutant with inactive phosphodiesterase (ns2-H126R) was assessed primary hepatocytes central nervous system (CNS) cell types-neurons, astrocytes, oligodendrocytes. ns2-H126R replicated similar kinetics all types tested, except macrophages microglia. RNase activity, by rRNA cleavage, induced ns2-H126R, but A59, only Activation correlated type I interferon consequent high levels OAS mRNA these types. Pretreatment nonmyeloid cells restricted to same extent failed activate infection, despite expression. However, degradation treatment astrocytes oligodendrocytes poly(I·C). Thus, during infection specific correlates relatively expression genes, which are necessary sufficient effective antiviral response.