+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Early endonuclease-mediated evasion of RNA sensing ensures efficient coronavirus replication



Early endonuclease-mediated evasion of RNA sensing ensures efficient coronavirus replication



Plos Pathogens 13(2): E1006195



Coronaviruses are of veterinary and medical importance and include highly pathogenic zoonotic viruses, such as SARS-CoV and MERS-CoV. They are known to efficiently evade early innate immune responses, manifesting in almost negligible expression of type-I interferons (IFN-I). This evasion strategy suggests an evolutionary conserved viral function that has evolved to prevent RNA-based sensing of infection in vertebrate hosts. Here we show that the coronavirus endonuclease (EndoU) activity is key to prevent early induction of double-stranded RNA (dsRNA) host cell responses. Replication of EndoU-deficient coronaviruses is greatly attenuated in vivo and severely restricted in primary cells even during the early phase of the infection. In macrophages we found immediate induction of IFN-I expression and RNase L-mediated breakdown of ribosomal RNA. Accordingly, EndoU-deficient viruses can retain replication only in cells that are deficient in IFN-I expression or sensing, and in cells lacking both RNase L and PKR. Collectively our results demonstrate that the coronavirus EndoU efficiently prevents simultaneous activation of host cell dsRNA sensors, such as Mda5, OAS and PKR. The localization of the EndoU activity at the site of viral RNA synthesis-within the replicase complex-suggests that coronaviruses have evolved a viral RNA decay pathway to evade early innate and intrinsic antiviral host cell responses.

Please choose payment method:






(PDF emailed within 1 workday: $29.90)

Accession: 059638322

Download citation: RISBibTeXText

PMID: 28158275


Related references

Heat Shock Protein 90 Ensures Efficient Mumps Virus Replication by Assisting with Viral Polymerase Complex Formation. Journal of Virology 91(6):, 2017

CRL4(WDR23)-Mediated SLBP Ubiquitylation Ensures Histone Supply during DNA Replication. Molecular Cell 62(4): 627-635, 2016

The nucleoprotein is required for efficient coronavirus genome replication. Journal of Virology 78(22): 12683-8, 2004

Kinetochore-dependent microtubule rescue ensures their efficient and sustained interactions in early mitosis. Developmental Cell 21(5): 920-933, 2011

Lipid-mediated introduction of hepatitis B virus capsids into nonsusceptible cells allows highly efficient replication and facilitates the study of early infection events. Journal of Virology 80(11): 5465-5473, 2006

Human cytomegalovirus tegument protein pUL83 inhibits IFI16-mediated DNA sensing for immune evasion. Cell Host and Microbe 14(5): 591-599, 2013

Anaphase-promoting complex/cyclosome-mediated proteolysis of Ams2 in the G1 phase ensures the coupling of histone gene expression to DNA replication in fission yeast. Journal of Biological Chemistry 288(2): 928-937, 2013

Efficient replication and generation of recombinant bovine adenovirus-3 in nonbovine cotton rat lung cells expressing I-SceI endonuclease. Journal of Gene Medicine 12(10): 840-847, 2010

Mouse hepatitis coronavirus RNA replication depends on GBF1-mediated ARF1 activation. Plos Pathogens 4(6): E1000088-E1000088, 2008

IFN-gamma-mediated suppression of coronavirus replication in glial-committed progenitor cells. Virology 384(1): 209-215, 2009

T cell mediated suppression of neurotropic coronavirus replication in neural precursor cells. Virology 449: 235-243, 2014

Efficient replication of severe acute respiratory syndrome coronavirus in mouse cells is limited by murine angiotensin-converting enzyme 2. Journal of Virology 78(20): 11429-11433, 2004

Acidosis promotes Bcl-2 family-mediated evasion of apoptosis: involvement of acid-sensing G protein-coupled receptor Gpr65 signaling to Mek/Erk. Journal of Biological Chemistry 287(33): 27863-27875, 2012

The intracellular sites of early replication and budding of SARS-coronavirus. Virology 361(2): 304-315, 2007

Early coronavirus polymerase proteins and their role in replication in a mouse model. Pediatric Research 27(4 Part 2): 169A, 1990