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

Research output: Contribution to journalArticlepeer-review

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), 2′-C-methylcytidine (2CMC) and NITD008 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 FCVURTD 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.

Original languageEnglish (US)
Article number2040
JournalViruses
Volume13
Issue number10
DOIs
StatePublished - Oct 2021

Keywords

  • 2′-C-methylcytidine
  • Caliciviridae
  • Nitazoxanide
  • NITD-008
  • Vesivirus

ASJC Scopus subject areas

  • Infectious Diseases
  • Virology

Fingerprint

Dive into the research topics of 'Feline calicivirus virulent systemic disease: Clinical epidemiology, analysis of viral isolates and in vitro efficacy of novel antivirals in australian outbreaks'. Together they form a unique fingerprint.

Cite this