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To initiate infection, many viruses enter their host cells by triggering endocytosis following receptor engagement. However, the mechanisms by which non-enveloped viruses escape the endosome are poorly understood. Here we present near-atomic-resolution cryo-electron microscopy structures for feline calicivirus both undecorated and labelled with a soluble fragment of its cellular receptor, feline junctional adhesion molecule A. We show that VP2, a minor capsid protein encoded by all caliciviruses 1 , 2 , forms a large portal-like assembly at a unique three-fold axis of symmetry, following receptor engagement. This assembly—which was not detected in undecorated virions—is formed of twelve copies of VP2, arranged with their hydrophobic N termini pointing away from the virion surface. Local rearrangement at the portal site leads to the opening of a pore in the capsid shell. We hypothesize that the portal-like assembly functions as a channel for the delivery of the calicivirus genome, through the endosomal membrane, into the cytoplasm of a host cell, thereby initiating infection. VP2 was previously known to be critical for the production of infectious virus 3 ; our findings provide insights into its structure and function that advance our understanding of the Caliciviridae . Cryo-electron microscopy structures of feline calicivirus and its cellular receptor show that twelve copies of the minor capsid protein VP2 form a portal-like assembly arranged about a pore in the capsid shell.

Feline calicivirus (FCV) is a highly contagious pathogen responsible for respiratory infections, lingual ulceration, oral ulcers and systemic diseases in cats, posing a significant risk to feline family worldwide. Virus enters via nasal oral and conjunctival routes. Oropharynx is primary site of replication, induces epithelial necrosis. After recovery from acute disease most cats clear virus within 30 days. Some lifelong carriers via colonization of tonsillar and other tissues. Understanding the structural and nonstructural proteins of FCV is essential to know viral replication process, its pathogenesis and interaction with host immune system. This manuscript outlines the recent progress made on the characterization of FCV proteins with respect to their involvement in viral assembly, entry, immune evasion, and replication. Although structural proteins such as capsid have received most attention regarding viral attachment and host specificity, but nonstructural proteins are emerging as key players in influencing host cell activities and viral RNA synthesis. This review highlights the requirement for advanced structural research methods, large-scale antiviral screening, and thorough investigations into FCV-host interactions. These studies will not only enable us fully understand FCV, but also promote the progress of more universally applicable virological research and drug development. Graphical abstract

•This study represents the largest prospective analysis of randomly sampled FCV in Europe.•The overall prevalence of FCV at a European level was 9.2% (7.8, 10.8, 95% confidence interval).•Several risk factors were positively associated with FCV shedding.•Phylogenetic analysis showed extensive variability and no countrywide clusters.•Plasma raised to the FCV-F9 vaccine strain neutralized 97% of field isolates at titres≥1:4. Feline calicivirus (FCV) is an important pathogen of cats for which vaccination is regularly practised. Long-term use of established vaccine antigens raises the theoretical possibility that field viruses could become resistant. This study aimed to assess the current ability of the FCV-F9 vaccine strain to neutralise a randomly collected contemporary panel of FCV field strains collected prospectively in six European countries. Veterinary practices (64) were randomly selected from six countries (UK, Sweden, Netherlands, Germany, France and Italy). Oropharyngeal swabs were requested from 30 (UK) and 40 (other countries) cats attending each practice. Presence of FCV was determined by virus isolation, and risk factors for FCV shedding assessed by multivariable logistic regression. Phylogenetic analyses were used to describe the FCV population structure. In vitro virus neutralisation assays were performed to evaluate FCV-F9 cross-reactivity using plasma from four vaccinated cats. The overall prevalence of FCV was 9.2%. Risk factors positively associated with FCV shedding included multi-cat households, chronic gingivostomatitis, younger age, not being neutered, as well as residing in certain countries. Phylogenetic analysis showed extensive variability and no countrywide clusters. Despite being first isolated in the 1950s, FCV-F9 clustered with contemporary field isolates. Plasma raised to FCV-F9 neutralized 97% of tested isolates (titres 1:4 to 1:5792), with 26.5%, 35.7% and 50% of isolates being neutralized by 5, 10 and 20 antibody units respectively. This study represents the largest prospective analysis of FCV diversity and antigenic cross-reactivity at a European level. The scale and random nature of sampling used gives confidence that the FCV isolates used are broadly representative of FCVs that cats are exposed to in these countries. The in vitro neutralisation results suggest that antibodies raised to FCV-F9 remain broadly cross-reactive to contemporary FCV isolates across the European countries sampled.

Feline calicivirus (FCV) is a significant pathogen in cats, with sporadic outbreaks of infections with virulent systemic (VS-FCV) strains causing significant health problems. Nineteen FCV strains were isolated and identified in China from 2021 to 2022. The nucleotide and amino acid phylogenetic analysis of the VP1 gene showed that 16 strains were GI genotype and three strains were GII genotype. HBDL2 strain was further found to be in the same clade as the reported VS-FCV SH/2014 strain, with 87.1% nucleotide sequence identity and 93.0% amino acid sequence identity. However, given that phylogenetic and homology analysis alone is insufficient to predict virulence, the pathogenic potential of HBDL2 was subsequently assessed through experimental infection in cats. The results revealed that HBDL2 was able to cause systemic clinical signs and caused severe tracheal and lung damage, with a similar characterization as the VS-FCV strain. Serum neutralization assays confirmed that HBDL2 elicited broad-spectrum neutralizing antibodies in cats against multiple FCV strains, including diverse GI and GII genotypes. Notably, neutralizing antibody titers against the VS-FCV strains were elevated. Additionally, we established an infectious clone of HBDL2 as a critical technical tool. These findings indicate that the HBDL2 strain holds promise for use in vaccine development against FCV infection.

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.

Feline calicivirus (FCV; ) is a highly contagious RNA virus that causes upper respiratory tract infections and intestinal symptoms in cats. In 2023 and 2024, in Shanghai (SH), China, we collected oral swab samples from 189 domestic cats exhibiting symptoms of upper respiratory tract disease (URTD), to test for five designated respiratory pathogens. Among the 111 cats testing positive for these pathogens, the FCV-positivity rate was 52% (58/111). Six FCV strains (three from SH and three from Guangdong [GD]) were successfully isolated from respiratory specimens from domestic cats. Whole genome sequencing and phylogenetic analyses revealed that these strains exhibited the GII FCV genotype, suggesting that this is the dominant genotype in Asia. Within the first 36 h postinfection, the GD strains exhibited faster growth and higher replication titers than the SH strains. The GD23-02 genotype (GD) and SH23-13 genotype (SH) exhibited intriguing amino acid variation in the VP1 E-region. We therefore selected these strains for challenge experiments. Although both strains caused oral-ulcer symptoms, they presented distinct disease progression and clinical manifestations; SH23-13 exhibited traits typical of virulent systemic disease (VSD), whereas GD23-02 predominantly exhibited symptoms of oral respiratory disease (ORD). Notably, both strains consistently induced severe diarrhea and intestinal damage, demonstrating the harmful effects of FCV on intestinal health. GD23-02 exhibited broad-spectrum neutralization capabilities, with antibody titers of 1:168 against the F9 vaccine GI strain and 1:2521 against the SH23-13 GII strain, making this a promising candidate for future vaccine formulation. These findings reveal the genetic diversity and complex pathogenicity of FCV isolates and elucidate the associations between FCV strains and intestinal disease. We recommend incorporating FCV testing into future diagnostic evaluation of feline diarrhea. This testing will be essential in elucidating the tissue specificity of FCV and potential escalation in its virulence.

Feline calicivirus (FCV) has a single-stranded, positive-sense RNA genome, and it is responsible for many infectious respiratory diseases in cats. In addition, more worryingly, highly virulent strains of FCV can cause high mortality in felines. Therefore, a rapid and reliable diagnosis tool plays an important role in controlling the outbreak of FCV. In this study, enzymatic recombinase amplification (ERA) assay combined with lateral flow dipstick (LFD) was developed for the detection of FCV, targeting a relatively conversed position of FCV- ORF1 . The results showed that the optimal reaction condition was at 40 °C for 30 min. ERA-LFD method was highly sensitive with the detection limit as low as 3.2 TCID 50 of FCV RNA per reaction. The specificity analysis demonstrated no cross-reactivity with feline parvovirus (FPV), feline herpesvirus (FHV) and feline infectious peritonitis virus (FIPV). ERA-LFD was highly repeatable and reproducible, with the intra-assay and inter-assay coefficients of variation for this method both less than 7%. The general test showed that all the recombinant plasmids with known mutant sites and FCV strains with different mutant sites stored in our laboratory were all detected by this method. Of the 23 samples, 14 samples were tested positive for FCV by ERA-LFD and RT-qPCR, respectively. In summary, ERA-LFD assay was a fast, accurate and convenient diagnosis tool for the detection of FCV. Key points • The detection principle of ERA-LFD was introduced. • Almost all the currently known FCV strains can be detected. • ERA-LFD is easy to operate and can be used for field detection.

A dielectric barrier discharge (DBD) plasma torch has been used to evaluate the mechanism underlying inactivation of feline calicivirus (FCV) by plasma treatment. Plasma treatment of cell lysate infected with FCV F9 strain reduced the viral titer of the median tissue culture infectious dose (TCID 50 ). The D value (treatment time required to lower the viral titer to 1/10) was 0.450 min, while the viral titer dropped below the detection limit within 2 min. FCV was not significantly inactivated by heat or UV applied at levels corresponding to those generated from the DBD plasma torch after 2 min (38.4 °C and 46.79 mJ/cm 2 UV, respectively). However, TCID 50 was reduced by 2.47 log after exposure to 4.62 mM ONOO − , corresponding to the concentration generated after 2 min of plasma treatment. Radical scavengers, including superoxide dismutase, dimethyl sulfoxide, and catalase, did not significantly affect viral titers; however, sodium azide, uric acid, and ascorbic acid, which are scavengers of 1 O 2 radicals, ONOO − , and peroxynitrous acid (ONOOH; produced from ONOO − under acidic conditions), respectively, significantly increased TCID 50 and intact viral RNA. These findings suggest that ONOO − and 1 O 2 play an important role in FCV inactivation by attacking viral RNA during DBD plasma torch treatment.

This study investigated a suspected Feline calicivirus (FCV) outbreak at a veterinary facility in Zhengzhou, Henan Province, China. RT-PCR analysis confirmed the FCV presence, with subsequent CRFK cell culture propagation leading to the isolation and characterization of strain ZZ202306. Immunofluorescence and Western blot analyses validated the specificity of monoclonal antibodies targeting the FCV VP1 capsid protein. Transmission electron microscopy revealed non-enveloped virions of ~40 nm in diameter, exhibiting typical caliciviral architecture. Viral replication kinetics demonstrated exponential growth between 6 and 18 h post-inoculation, reaching a peak titer of 107.96 TCID50/0.1 mL. Genomic sequencing coupled with phylogenetic reconstruction of the VP1 gene revealed a close genetic relation to domestic Chinese strains and international variants, while maintaining distinct evolutionary divergence from other calicivirus genera.

Feline calicivirus (FCV) is a highly infectious pathogen that causes upper respiratory tract disease (URTD), with a higher prevalence in group-housed cats compared to those raised individually. In this study, 15 FCV strains were isolated from group-housed cats exhibiting URTD symptoms in Changzhou, China, in 2024. Phylogenetic analysis based on the VP1 sequences revealed that 13 of 15 strains clustered within genogroup I (G I), while none belonged to genogroup II (G II). Notably, the remaining two strains grouped with several recently published Chinese isolates, forming an independent branch distinct from both G I and G II, proposed as genogroup III (G III). The VP1 proteins of the 13 G I strains exhibited specific residues 377N, 539A, and 557G, consistent with the established G I-specific markers (377N/S, 539A/P, and 557G). In contrast, G II strains typically retain 377 K, 539 V, and 557S. Interestingly, the G III strains displayed 377N, 539A (specific to G I) and 557S (specific to G II). Recombinant analysis found that co-circulating G I and G III resulted in a recombinant strain. Furthermore, neutralization tests demonstrated poor cross-neutralization between G I and G III strains. This study provides valuable insights for the development of effective vaccination strategies.