Rotavirus controls activation of the 2'-5'-oligoadenylate synthetase/RNase L pathway using at least two distinct mechanisms
Por:
SanchezTacuba, L, Rojas, M, Arias, CF, Lopez, S
Publicada:
1 dic 2015
Resumen:
The innate immune response is the first line of defense of the host cell against a viral infection. In turn, viruses have evolved a wide variety of strategies to hide from, and to directly antagonize, the host innate immune pathways. One of these pathways is the 2'-5'-oligoadenylate synthetase (OAS)/RNase L pathway. OAS is activated by double-stranded RNA (dsRNA) to produce 2'-5' oligoadenylates, which are the activators of RNase L; this enzyme degrades viral and cellular RNAs, restricting viral infection. It has been recently found that the carboxy-terminal domain (CTD) of rotavirus VP3 has a 2'-5'-phosphodiesterase (PDE) activity that is able to functionally substitute for the PDE activity of the mouse hepatitis virus ns2 protein. This particular phosphodiesterase cleaves the 2'-5'-phosphodiester bond of the oligoadenylates, antagonizing the OAS/RNase L pathway. However, whether this activity of VP3 is relevant during the replication cycle of rotavirus is not known. Here, we demonstrate that after rotavirus infection the OAS/RNase L complex becomes activated; however, the virus is able to control its activity using at least two distinct mechanisms. A virus-cell interaction that occurs during or before rotavirus endocytosis triggers a signal that prevents the early activation of RNase L, while later on the control is taken by the newly synthesized VP3. Cosilencing the expression of VP3 and RNase L in infected cells yields viral infectious particles at levels similar to those obtained in control infected cells, where no genes were silenced, suggesting that the capping activity of VP3 is not essential for the formation of infectious viral particles. © 2015, American Society for Microbiology.
Filiaciones:
SanchezTacuba, L:
Univ Nacl Autonoma Mexico, Inst Biotecnol, Dept Genet Desarrollo & Fisiol Mol, Cuernavaca 62191, Morelos, Mexico
Rojas, M:
Univ Nacl Autonoma Mexico, Inst Biotecnol, Dept Genet Desarrollo & Fisiol Mol, Cuernavaca 62191, Morelos, Mexico
Arias, CF:
Univ Nacl Autonoma Mexico, Inst Biotecnol, Dept Genet Desarrollo & Fisiol Mol, Cuernavaca 62191, Morelos, Mexico
Lopez, S:
Univ Nacl Autonoma Mexico, Inst Biotecnol, Dept Genet Desarrollo & Fisiol Mol, Cuernavaca 62191, Morelos, Mexico
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