Homodimerisation-independent cleavage of dsRNA by a pestiviral nicking endoribonuclease.

Lussi, Carmela; Sauter, Kay Sara; Schweizer, Matthias (2018). Homodimerisation-independent cleavage of dsRNA by a pestiviral nicking endoribonuclease. Scientific Reports, 8(1), p. 8226. Nature Publishing Group 10.1038/s41598-018-26557-4

[img]
Preview
Text
s41598-018-26557-4.pdf - Published Version
Available under License Creative Commons: Attribution (CC-BY).

Download (2MB) | Preview

The glycoprotein E plays a central role in the biology of the pestivirus bovine viral diarrhea virus (BVDV). This soluble endonuclease mediates the escape from an interferon (IFN) response in the infected fetus, thereby permitting the establishment of persistent infection. Viral single-stranded (ss) and double-stranded (ds) RNA act as potent IFN inducing signals and we previously showed that E efficiently cleaves these substrates, thereby inhibiting an IFN response that is crucial for successful fetal infection. Considering that a large variety of RNases and DNases require dimerisation to cleave double-stranded substrates, the activity of E against dsRNA was postulated to depend on homodimer formation mediated by disulfide bonds involving residue Cys171. Here, we show that monomeric E is equally able to cleave dsRNA and to inhibit dsRNA-induced IFN synthesis as the wild-type form. Furthermore, both forms were able to degrade RNA within a DNA/RNA- as well as within a methylated RNA/RNA-hybrid, with the DNA and the methylated RNA strand being resistant to degradation. These results support our model that E acts as 'nicking endoribonuclease' degrading ssRNA within double-stranded substrates. This efficiently prevents the activation of IFN and helps to maintain a state of innate immunotolerance in persistently infected animals.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Virology and Immunology
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP)

UniBE Contributor:

Lussi, Carmela; Sauter, Kay Sara and Schweizer, Matthias

Subjects:

600 Technology > 630 Agriculture

ISSN:

2045-2322

Publisher:

Nature Publishing Group

Language:

English

Submitter:

Monika Mumenthaler

Date Deposited:

17 Dec 2018 09:37

Last Modified:

23 Dec 2018 02:33

Publisher DOI:

10.1038/s41598-018-26557-4

PubMed ID:

29844335

BORIS DOI:

10.7892/boris.122119

URI:

https://boris.unibe.ch/id/eprint/122119

Actions (login required)

Edit item Edit item
Provide Feedback