Author:
Keep Sarah,Carr Brigid Veronica,Lean Fabian Z. X.,Fones Albert,Newman Joseph,Dowgier Giulia,Freimanis Graham,Vatzia Eleni,Polo Noemi,Everest Holly,Webb Isobel,Mcnee Adam,Paudyal Basu,Thakur Nazia,Nunez Alejandro,MacLoughlin Ronan,Maier Helena,Hammond John,Bailey Dalan,Waters Ryan,Charleston Bryan,Tuthill Toby,Britton Paul,Bickerton Erica,Tchilian Elma
Abstract
In the light of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, we have developed a porcine respiratory coronavirus (PRCV) model for in depth mechanistic evaluation of the pathogenesis, virology and immune responses of this important family of viruses. Pigs are a large animal with similar physiology and immunology to humans and are a natural host for PRCV. Four PRCV strains were investigated and shown to induce different degrees of lung pathology. Importantly, although all four strains replicated equally well in porcine cell linesin vitroand in the upper respiratory tractin vivo, PRCV strains causing more severe lung pathology were also able to replicate inex vivotracheal organ cultures as well asin vivoin the trachea and lung. The time course of infection of PRCV 135, which caused the most severe pulmonary pathology, was investigated. Virus was shed from the upper respiratory tract until day 10 post infection, with infection of the respiratory mucosa, as well as olfactory and sustentacular cells, providing an excellent model to study upper respiratory tract disease in addition to the commonly known lower respiratory tract disease from PRCV. Infected animals made antibody and T cell responses that cross reacted with the four PRCV strains and Transmissible Gastroenteritis Virus. The antibody response was reproducedin vitroin organ cultures. Comparison of mechanisms of infection and immune control in pigs infected with PRCVs of differing pathogenicity with human data from SARS-CoV-2 infection and from ourin vitroorgan cultures, will enable key events in coronavirus infection and disease pathogenesis to be identified.
Funder
Biotechnology and Biological Sciences Research Council
Subject
Immunology,Immunology and Allergy
Cited by
11 articles.
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