Experimental feline enteric coronavirus infection reveals an aberrant infection pattern and shedding of mutants with impaired infectivity in enterocyte cultures

Desmarets, Lowiese; Vermeulen, Ben; Theuns, Sebastiaan; Conceição-Neto, Nádia; Zeller, Mark; Roukaerts, Inge; Acar, Delphine D.; Olyslaegers, Dominique; Ranst, Marc Van; Matthijnssens, Jelle; Nauwynck, Hans

doi:10.1038/srep20022

Cited by 41 publications

(42 citation statements)

References 48 publications

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“…Detection of FCoV by RT-qPCR in colonic tissue of 3 cats without FIP was not surprising as enteric infection has been described in otherwise clinically healthy cats [7,8,32]. These 3 cats were euthanized as a result of clinical signs relating to pyothorax, brain tumour and nasal adenocarcinoma, had unremarkable histopathological examination and negative IHC of colonic tissue.…”

Section: Discussionmentioning

confidence: 94%

Limitations of using feline coronavirus spike protein gene mutations to diagnose feline infectious peritonitis

Barker

Stranieri

Helps

et al. 2017

Vet Res

127

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Feline infectious peritonitis (FIP) is a fatal disease of cats, and a sequela of systemic feline coronavirus (FCoV) infection. Mutations in the viral spike (S) gene have been associated with FCoVs found in tissues from cats with FIP, but not FCoVs found in faeces from healthy cats, and are implicated in monocyte/macrophage tropism and systemic spread. This study was designed to determine whether S gene mutation analysis can reliably diagnose FIP. Cats were categorised as with FIP (n = 57) or without FIP (n = 45) based on gross post-mortem and histopathological examination including immunohistochemistry for FCoV antigen. RNA was purified from available tissue, fluid and faeces. Reverse-transcriptase quantitative-PCR (RT-qPCR) was performed on all samples using FCoV-specific primers, followed by sequencing of a section of the S gene on RT-qPCR positive samples. Samples were available from a total of 102 cats. Tissue, fluid, and faecal samples from cats with FIP were more likely to be FCoV RT-qPCR-positive (90.4, 78.4 and 64.6% respectively) than those from cats without FIP (7.8, 2.1 and 20% respectively). Identification of S gene mutated FCoVs as an additional step to the detection of FCoV alone, only moderately increased specificity for tissue samples (from 92.6 to 94.6%) but specificity was unchanged for fluid samples (97.9%) for FIP diagnosis; however, sensitivity was markedly decreased for tissue (from 89.8 to 80.9%) and fluid samples (from 78.4 to 60%) for FIP diagnosis. These findings demonstrate that S gene mutation analysis in FCoVs does not substantially improve the ability to diagnose FIP as compared to detection of FCoV alone.Electronic supplementary materialThe online version of this article (doi:10.1186/s13567-017-0467-9) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 94%

Limitations of using feline coronavirus spike protein gene mutations to diagnose feline infectious peritonitis

Barker

Stranieri

Helps

et al. 2017

Vet Res

127

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“…Mutations in other parts of the S 2 subunit than those affecting the proteolytic cleavage sites may also influence the tropism of different CoVs. Several studies report a correlation between mutations in the HR1 region of FCoVs and the conversion of FECV into FIPV (Bank-Wolf et al, 2014;Desmarets et al, 2016;Lewis et al, 2015). Such a correlation appeared even more convincing for mutations found in the recently identified FP2 (Chang et al, 2012;Ou et al, 2016).…”

Section: Other S 2 Mutations Associated With Altered Tropismmentioning

confidence: 89%

Coronavirus Spike Protein and Tropism Changes

Hulswit

Haan

Bosch

2016

Advances in Virus Research

432

404

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Coronaviruses (CoVs) have a remarkable potential to change tropism. This is particularly illustrated over the last 15 years by the emergence of two zoonotic CoVs, the severe acute respiratory syndrome (SARS)- and Middle East respiratory syndrome (MERS)-CoV. Due to their inherent genetic variability, it is inevitable that new cross-species transmission events of these enveloped, positive-stranded RNA viruses will occur. Research into these medical and veterinary important pathogens-sparked by the SARS and MERS outbreaks-revealed important principles of inter- and intraspecies tropism changes. The primary determinant of CoV tropism is the viral spike (S) entry protein. Trimers of the S glycoproteins on the virion surface accommodate binding to a cell surface receptor and fusion of the viral and cellular membrane. Recently, high-resolution structures of two CoV S proteins have been elucidated by single-particle cryo-electron microscopy. Using this new structural insight, we review the changes in the S protein that relate to changes in virus tropism. Different concepts underlie these tropism changes at the cellular, tissue, and host species level, including the promiscuity or adaptability of S proteins to orthologous receptors, alterations in the proteolytic cleavage activation as well as changes in the S protein metastability. A thorough understanding of the key role of the S protein in CoV entry is critical to further our understanding of virus cross-species transmission and pathogenesis and for development of intervention strategies.

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“…In several cases, FECVs remained detectable in the feces of the cats for more than 15 weeks, although with decreasing viral loads. To investigate the course of infection in more detail, FECV infection experiments have also been performed under controlled conditions (Desmarets et al, 2016;Kipar et al, 2010;Pedersen et al, 2008;Vogel et al, 2010). These studies showed that FECVs induce symptomless persistent infections similar to natural infections.…”

Section: Feline Enteric Coronavirusmentioning

confidence: 99%

Feline Coronaviruses

Tekes

Thiel

2016

Advances in Virus Research

124

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Feline infectious peritonitis (FIP) belongs to the few animal virus diseases in which, in the course of a generally harmless persistent infection, a virus acquires a small number of mutations that fundamentally change its pathogenicity, invariably resulting in a fatal outcome. The causative agent of this deadly disease, feline infectious peritonitis virus (FIPV), arises from feline enteric coronavirus (FECV). The review summarizes our current knowledge of the genome and proteome of feline coronaviruses (FCoVs), focusing on the viral surface (spike) protein S and the five accessory proteins. We also review the current classification of FCoVs into distinct serotypes and biotypes, cellular receptors of FCoVs and their presumed role in viral virulence, and discuss other aspects of FIPV-induced pathogenesis. Our current knowledge of genetic differences between FECVs and FIPVs has been mainly based on comparative sequence analyses that revealed "discriminatory" mutations that are present in FIPVs but not in FECVs. Most of these mutations result in amino acid substitutions in the S protein and these may have a critical role in the switch from FECV to FIPV. In most cases, the precise roles of these mutations in the molecular pathogenesis of FIP have not been tested experimentally in the natural host, mainly due to the lack of suitable experimental tools including genetically engineered virus mutants. We discuss the recent progress in the development of FCoV reverse genetics systems suitable to generate recombinant field viruses containing appropriate mutations for in vivo studies.

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Experimental feline enteric coronavirus infection reveals an aberrant infection pattern and shedding of mutants with impaired infectivity in enterocyte cultures

Cited by 41 publications

References 48 publications

Limitations of using feline coronavirus spike protein gene mutations to diagnose feline infectious peritonitis

Limitations of using feline coronavirus spike protein gene mutations to diagnose feline infectious peritonitis

Coronavirus Spike Protein and Tropism Changes

Feline Coronaviruses

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