Emergence and spread of feline infectious peritonitis due to a highly pathogenic canine/feline recombinant coronavirus

Cross-species transmission of coronaviruses (CoVs) poses a serious threat to both animal and human health1-3. Whilst the large RNA genome of CoVs shows relatively low mutation rates, recombination within genera is frequently observed and demonstrated4-7. Companion animals are often overlooked in the transmission cycle of viral diseases; however, the close relationship of feline (FCoV) and canine CoV (CCoV) to human hCoV-229E5,8, as well as their susceptibility to SARS-CoV-29 highlight their importance in potential transmission cycles. Whilst recombination between CCoV and FCoV of a large fragment spanning orf1b to M has been previously described5,10, here we report the emergence of a novel, highly pathogenic FCoV-CCoV recombinant responsible for a rapidly spreading outbreak of feline infectious peritonitis (FIP), originating in Cyprus11. The recombination, spanning spike, shows 97% sequence identity to the pantropic canine coronavirus CB/05. Infection is spreading fast and infecting cats of all ages. Development of FIP appears rapid and likely non-reliant on biotype switch12. High sequence identity of isolates from cats in different districts of the island is strongly supportive of direct transmission. A deletion and several amino acid changes in spike, particularly the receptor binding domain, compared to other FCoV-2s, indicate changes to receptor binding and likely cell tropism.

[1]  K. Jeevaratnam,et al.  Retrospective study and outcome of 307 cats with feline infectious peritonitis treated with legally sourced veterinary compounded preparations of remdesivir and GS-441524 (2020–2022) , 2023, Journal of feline medicine and surgery.

[2]  E. Thiry,et al.  Feline Infectious Peritonitis: European Advisory Board on Cat Diseases Guidelines , 2023, Viruses.

[3]  S. Mazeri,et al.  Concerning feline infectious peritonitis outbreak in Cyprus. , 2023, The Veterinary record.

[4]  M. Stanhope,et al.  Natural selection differences detected in key protein domains between non-pathogenic and pathogenic feline coronavirus phenotypes , 2023, Virus evolution.

[5]  H. Zhao,et al.  An updated review of feline coronavirus: mind the two biotypes , 2023, Virus research.

[6]  Panagiotis I. Koukos,et al.  Pathogen-sugar interactions revealed by universal saturation transfer analysis , 2022, Science.

[7]  M. R. Mananggit,et al.  No part gets left behind: Tiled nanopore sequencing of whole ASFV genomes stitched together using Lilo , 2021, bioRxiv.

[8]  B. Braeckman,et al.  Amplicon_sorter: A tool for reference‐free amplicon sorting based on sequence similarity and for building consensus sequences , 2021, Ecology and evolution.

[9]  P. Bork,et al.  Interactive Tree Of Life (iTOL) v5: an online tool for phylogenetic tree display and annotation , 2021, Nucleic Acids Res..

[10]  B. Murphy,et al.  Coronavirus Infections in Companion Animals: Virology, Epidemiology, Clinical and Pathologic Features , 2020, Viruses.

[11]  J. Skehel,et al.  SARS-CoV-2 and bat RaTG13 spike glycoprotein structures inform on virus evolution and furin-cleavage effects , 2020, Nature Structural & Molecular Biology.

[12]  Ben Murrell,et al.  RDP5: a computer program for analyzing recombination in, and removing signals of recombination from, nucleotide sequence datasets , 2020, Virus evolution.

[13]  S. Perlman,et al.  Distinct Roles for Sialoside and Protein Receptors in Coronavirus Infection , 2020, mBio.

[14]  G. Whittaker,et al.  A Tale of Two Viruses: The Distinct Spike Glycoproteins of Feline Coronaviruses , 2020, Viruses.

[15]  C. Sánchez,et al.  Minimum Determinants of Transmissible Gastroenteritis Virus Enteric Tropism Are Located in the N-Terminus of Spike Protein , 2019, Pathogens.

[16]  S. Xiao,et al.  The N-Terminal Domain of Spike Protein Is Not the Enteric Tropism Determinant for Transmissible Gastroenteritis Virus in Piglets , 2019, Viruses.

[17]  A. Vlasova,et al.  Emerging and re-emerging coronaviruses in pigs , 2019, Current Opinion in Virology.

[18]  H. Amer Bovine-like coronaviruses in domestic and wild ruminants , 2018, Animal Health Research Reviews.

[19]  V. Corman,et al.  Hosts and Sources of Endemic Human Coronaviruses , 2018, Advances in Virus Research.

[20]  G. Whittaker,et al.  Feline coronavirus: Insights into viral pathogenesis based on the spike protein structure and function , 2018, Virology.

[21]  Evan Bolton,et al.  Database resources of the National Center for Biotechnology Information , 2017, Nucleic Acids Res..

[22]  Elliot J. Lefkowitz,et al.  Virus taxonomy: the database of the International Committee on Taxonomy of Viruses (ICTV) , 2017, Nucleic Acids Res..

[23]  Heng Li,et al.  Minimap2: pairwise alignment for nucleotide sequences , 2017, Bioinform..

[24]  Trevor Bedford,et al.  Multiplex PCR method for MinION and Illumina sequencing of Zika and other virus genomes directly from clinical samples , 2017, Nature Protocols.

[25]  O. Pybus,et al.  Exploring the temporal structure of heterochronous sequences using TempEst (formerly Path-O-Gen) , 2016, Virus evolution.

[26]  A. von Haeseler,et al.  IQ-TREE: A Fast and Effective Stochastic Algorithm for Estimating Maximum-Likelihood Phylogenies , 2014, Molecular biology and evolution.

[27]  H. Shimoda,et al.  Emergence of Pathogenic Coronaviruses in Cats by Homologous Recombination between Feline and Canine Coronaviruses , 2014, PloS one.

[28]  Bas E. Dutilh,et al.  Combining de novo and reference-guided assembly with scaffold_builder , 2013, Source Code for Biology and Medicine.

[29]  C. Buonavoglia,et al.  Molecular characterization of a canine coronavirus NA/09 strain detected in a dog’s organs , 2011, Archives of Virology.

[30]  S. le Poder Feline and Canine Coronaviruses: Common Genetic and Pathobiological Features , 2011, Advances in virology.

[31]  Helga Thorvaldsdóttir,et al.  Integrative Genomics Viewer , 2011, Nature Biotechnology.

[32]  M. Marinaro,et al.  Prolonged depletion of circulating CD4+ T lymphocytes and acute monocytosis after pantropic canine coronavirus infection in dogs , 2010, Virus Research.

[33]  P. Woo,et al.  Coronavirus Diversity, Phylogeny and Interspecies Jumping , 2009, Experimental biology and medicine.

[34]  L. Enjuanes,et al.  Recombinant Canine Coronaviruses Related to Transmissible Gastroenteritis Virus of Swine Are Circulating in Dogs , 2008, Journal of Virology.

[35]  V. Martella,et al.  Molecular characterisation of the virulent canine coronavirus CB/05 strain , 2007, Virus Research.

[36]  K. Crandall,et al.  A modified bootscan algorithm for automated identification of recombinant sequences and recombination breakpoints. , 2005, AIDS research and human retroviruses.

[37]  K. Katoh,et al.  MAFFT: a novel method for rapid multiple sequence alignment based on fast Fourier transform. , 2002, Nucleic acids research.

[38]  C. Sánchez,et al.  Targeted Recombination Demonstrates that the Spike Gene of Transmissible Gastroenteritis Coronavirus Is a Determinant of Its Enteric Tropism and Virulence , 1999, Journal of Virology.

[39]  H. Lutz,et al.  One-tube fluorogenic reverse transcription-polymerase chain reaction for the quantitation of feline coronaviruses , 1999, Journal of Virological Methods.

[40]  L. Enjuanes,et al.  Transmissible gastroenteritis coronavirus, but not the related porcine respiratory coronavirus, has a sialic acid (N-glycolylneuraminic acid) binding activity , 1996, Journal of virology.

[41]  John Maynard Smith,et al.  Analyzing the mosaic structure of genes , 1992, Journal of Molecular Evolution.

[42]  E. Myers,et al.  Basic local alignment search tool. , 1990, Journal of molecular biology.

[43]  J. Descôteaux,et al.  An enteric coronavirus of the rabbit: Detection by immunoelectron microscopy and identification of structural polypeptides , 2005, Archives of Virology.

[44]  R. Woods,et al.  Relatedness of rabbit coronavirus to other coronaviruses. , 1987, Advances in experimental medicine and biology.