Abrogation of the RNase activity of Erns in a low virulence classical swine fever virus enhances the humoral immune response and reduces virulence, transmissibility, and persistence in pigs.

Wang, Miaomiao; Bohórquez, José Alejandro; Hinojosa, Yoandry; Muñoz-González, Sara; Gerber, Markus; Coronado, Liani; Perera, Carmen Laura; Liniger, Matthias; Ruggli, Nicolas; Ganges, Llilianne (2021). Abrogation of the RNase activity of Erns in a low virulence classical swine fever virus enhances the humoral immune response and reduces virulence, transmissibility, and persistence in pigs. Virulence, 12(1), pp. 2037-2049. Taylor & Francis 10.1080/21505594.2021.1959715

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

Download (2MB) | Preview

The prevalence of low virulence classical swine fever virus (CSFV) strains makes viral eradication difficult in endemic countries. However, the determinants for natural CSFV attenuation and persistence in the field remain unidentified. The aim of the present study was to assess the role of the RNase activity of CSFV Erns in pathogenesis, immune response, persistent infection, and viral transmission in pigs. To this end, a functional cDNA clone pPdR-H30K-36U with an Erns lacking RNase activity was constructed based on the low virulence CSFV field isolate Pinar de Rio (PdR). Eighteen 5-day-old piglets were infected with vPdR-H30K-36U. Nine piglets were introduced as contacts. The vPdR-H30K-36U virus was attenuated in piglets compared to the parental vPdR-36U. Only RNA traces were detected in sera and body secretions and no virus was isolated from tonsils, showing that RNase inactivation may reduce CSFV persistence and transmissibility. The vPdR-H30K-36U mutant strongly activated the interferon-α (IFN-α) production in plasmacytoid dendritic cells, while in vivo, the IFN-α response was variable, from moderate to undetectable depending on the animal. This suggests a role of the CSFV Erns RNase activity in the regulation of innate immune responses. Infection with vPdR-H30K-36U resulted in higher antibody levels against the E2 and Erns glycoproteins and in enhanced neutralizing antibody responses when compared with vPdR-36U. These results pave the way toward a better understanding of viral attenuation mechanisms of CSFV in pigs. In addition, they provide novel insights relevant for the development of DIVA vaccines in combination with diagnostic assays for efficient CSF control.

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)

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Gerber, Markus (A), Liniger, Matthias, Ruggli, Nicolas

Subjects:

500 Science > 570 Life sciences; biology
500 Science > 590 Animals (Zoology)
600 Technology > 610 Medicine & health
600 Technology > 630 Agriculture

ISSN:

2150-5608

Publisher:

Taylor & Francis

Language:

English

Submitter:

Pamela Schumacher

Date Deposited:

18 Nov 2021 10:06

Last Modified:

31 Jan 2023 23:37

Publisher DOI:

10.1080/21505594.2021.1959715

PubMed ID:

34339338

Uncontrolled Keywords:

Classical swine fever virus (CSFV) Erns RNase activity Pestivirus humoral response type I IFN viral attenuation viral persistence viral replication viral transmission

BORIS DOI:

10.48350/160717

URI:

https://boris.unibe.ch/id/eprint/160717

Actions (login required)

Edit item Edit item
Provide Feedback