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FELINE CALICIVIRUS VIRULENT SYSTEMIC DISEASE: CLINICAL EPIDEMIOLOGY, ANALYSIS OF VIRAL ISOLATES AND IN VITRO EFFICACY OF NOVEL ANTIVIRALS IN AUSTRALIAN OUTBREAKS
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Faculty of Science, Sydney School of Veterinary Science, The University of Sydney. Sydney, NSW 2006, Australia.
Faculty of Science, School of Biotechnology and Biomolecular Sciences, University of New South Wales. Sydney, NSW 2052, Australia / Fundação Oswaldo Cruz, Instituto Oswaldo Cruz. Laboratório de Virologia Comparada e Ambiental. Rio de Janeiro, RJ, Brasil.
Faculty of Science, Sydney School of Veterinary Science, The University of Sydney. Sydney, NSW 2006, Australia / Marie Bashir Institute for Infectious Diseases and Biosecurity, School of Life and Environmental Sciences and School of Medical Sciences, University of Sydney. Sydney, Australia.
Faculty of Science, School of Biotechnology and Biomolecular Sciences, University of New South Wales. Sydney, NSW 2052, Australia
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, China.
School of Medicine, Sun Yat-sen University Guangzhou East Campus, Panyu, Guangzhou 510080, China.
Department of Pathology, Microbiology and Immunology, UC Davis School of Veterinary Medicine, 1044 Haring Hall, 1 Shields Avenue. Davis, CA, USA.
Marie Bashir Institute for Infectious Diseases and Biosecurity, School of Life and Environmental Sciences and School of Medical Sciences, University of Sydney. Sydney, Australia.
University of Aldo Moro of Bari. Department of Veterinary Medicine. Valenzano, Italia.
Faculty of Science, School of Biotechnology and Biomolecular Sciences, University of New South Wales. Sydney, NSW 2052, Australia.
Faculty of Science, Sydney School of Veterinary Science, The University of Sydney. Sydney, NSW 2006, Australia / 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, China.
School of Medicine, Sun Yat-sen University Guangzhou East Campus, Panyu, Guangzhou 510080, China.
Faculty of Science, Sydney School of Veterinary Science, The University of Sydney. Sydney, NSW 2006, Australia / 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, China.
Faculty of Science, School of Biotechnology and Biomolecular Sciences, University of New South Wales. Sydney, NSW 2052, Australia / Fundação Oswaldo Cruz, Instituto Oswaldo Cruz. Laboratório de Virologia Comparada e Ambiental. Rio de Janeiro, RJ, Brasil.
Faculty of Science, Sydney School of Veterinary Science, The University of Sydney. Sydney, NSW 2006, Australia / Marie Bashir Institute for Infectious Diseases and Biosecurity, School of Life and Environmental Sciences and School of Medical Sciences, University of Sydney. Sydney, Australia.
Faculty of Science, School of Biotechnology and Biomolecular Sciences, University of New South Wales. Sydney, NSW 2052, Australia
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, China.
School of Medicine, Sun Yat-sen University Guangzhou East Campus, Panyu, Guangzhou 510080, China.
Department of Pathology, Microbiology and Immunology, UC Davis School of Veterinary Medicine, 1044 Haring Hall, 1 Shields Avenue. Davis, CA, USA.
Marie Bashir Institute for Infectious Diseases and Biosecurity, School of Life and Environmental Sciences and School of Medical Sciences, University of Sydney. Sydney, Australia.
University of Aldo Moro of Bari. Department of Veterinary Medicine. Valenzano, Italia.
Faculty of Science, School of Biotechnology and Biomolecular Sciences, University of New South Wales. Sydney, NSW 2052, Australia.
Faculty of Science, Sydney School of Veterinary Science, The University of Sydney. Sydney, NSW 2006, Australia / 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, China.
School of Medicine, Sun Yat-sen University Guangzhou East Campus, Panyu, Guangzhou 510080, China.
Faculty of Science, Sydney School of Veterinary Science, The University of Sydney. Sydney, NSW 2006, Australia / 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, China.
Abstract
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 FCVVSD
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), 20-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 M,
TI = 21; 2CMC EC50, 2.7–5.3 M, TI > 18; NITD-008, 0.5 to 0.9 M, TI > 111. Investigation of these
antivirals for the treatment of FCV-VSD is warranted.
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