Feline Calicivirus Virulent Systemic Disease: Clinical Epidemiology, Analysis of Viral Isolates and In Vitro Efficacy of Novel Antivirals in Australian Outbreaks
Matteo Bordicchia,
Tulio Machado Fumian,
Kate Van Brussel,
Alice G. Russo,
Maura Carrai,
Shi-Jia Le,
Patricia A. Pesavento,
Edward C. Holmes,
Vito Martella,
Peter White,
Julia A. Beatty,
Mang Shi,
Vanessa R. Barrs
Affiliations
Matteo Bordicchia
Faculty of Science, Sydney School of Veterinary Science, The University of Sydney, Sydney, NSW 2006, Australia
Tulio Machado Fumian
Faculty of Science, School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW 2052, Australia
Kate Van Brussel
Faculty of Science, Sydney School of Veterinary Science, The University of Sydney, Sydney, NSW 2006, Australia
Alice G. Russo
Faculty of Science, School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW 2052, Australia
Maura Carrai
Department of Veterinary Clinical Sciences, Jockey Club College of Veterinary Medicine and Life Sciences, Centre for Companion Animal Health, City University of Hong Kong, Kowloon Tong, Hong Kong 999077, China
Shi-Jia Le
School of Medicine, Sun Yat-sen University Guangzhou East Campus, Panyu, Guangzhou 510080, China
Patricia A. Pesavento
Department of Pathology, Microbiology and Immunology, UC Davis School of Veterinary Medicine, 1044 Haring Hall, 1 Shields Avenue, Davis, CA 95616, USA
Edward C. Holmes
Marie Bashir Institute for Infectious Diseases and Biosecurity, School of Life and Environmental Sciences and School of Medical Sciences, University of Sydney, Sydney, NSW 2006, Australia
Vito Martella
Department of Veterinary Medicine, University of Aldo Moro of Bari, 70010 Valenzano, Italy
Peter White
Faculty of Science, School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW 2052, Australia
Julia A. Beatty
Faculty of Science, Sydney School of Veterinary Science, The University of Sydney, Sydney, NSW 2006, Australia
Mang Shi
School of Medicine, Sun Yat-sen University Guangzhou East Campus, Panyu, Guangzhou 510080, China
Vanessa R. Barrs
Faculty of Science, Sydney School of Veterinary Science, The University of Sydney, Sydney, NSW 2006, Australia
Feline calicivirus (FCV) causes upper respiratory tract disease (URTD) and sporadic outbreaks of virulent systemic disease (FCV-VSD). The basis for the increased pathogenicity of FCV-VSD viruses is incompletely understood, and antivirals for FCV-VSD have yet to be developed. We investigated the clinicoepidemiology and viral features of three FCV-VSD outbreaks in Australia and evaluated the in vitro efficacy of nitazoxanide (NTZ), 2′-C-methylcytidine (2CMC) and NITD-008 against FCV-VSD viruses. Overall mortality among 23 cases of FCV-VSD was 39%. Metagenomic sequencing identified five genetically distinct FCV lineages within the three outbreaks, all seemingly evolving in situ in Australia. Notably, no mutations that clearly distinguished FCV-URTD from FCV-VSD phenotypes were identified. One FCV-URTD strain likely originated from a recombination event. Analysis of seven amino-acid residues from the hypervariable E region of the capsid in the cultured viruses did not support the contention that properties of these residues can reliably differentiate between the two pathotypes. On plaque reduction assays, dose–response inhibition of FCV-VSD was obtained with all antivirals at low micromolar concentrations; NTZ EC50, 0.4–0.6 µM, TI = 21; 2CMC EC50, 2.7–5.3 µM, TI > 18; NITD-008, 0.5 to 0.9 µM, TI > 111. Investigation of these antivirals for the treatment of FCV-VSD is warranted.
