Mutations in the 3c and 7b genes of feline coronavirus in spontaneously affected FIP cats

Borschensky, C.; Reinacher, M.

doi:10.1016/j.rvsc.2014.07.016

Cited by 25 publications

(32 citation statements)

References 41 publications

(74 reference statements)

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“…This study did not determine whether any faecally shed FCoV was infective; this is an important concept as faeces containing mutated FCoV theoretically has increased potential to cause FIP following faecooral transmission, assuming the mutated virus can enter enterocytes and replicate. Previous studies have reported 39-85% of FCoVs detected in tissues from cats with FIP had loss of 3c gene functionality [33][34][35], which has been associated with a loss of ability to replicate in enterocytes and therefore infectivity via the natural route [35,36]. Enterocyte cell cultures have been used to more accurately assess FCoV infectivity and virus copy number in a recent study [8].…”

Section: Discussionmentioning

confidence: 99%

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: 99%

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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“…It is generally accepted that the basic reason for the development of FIP syndromes is the enhanced replication rate of FIP virus (FIPV) in monocytes and macrophages. In the case of FECV/FIPV, the shifting of the focus of viral replication from the intestinal tract toward macrophages and monocytes usually goes hand in hand with deletions in the genomic regions 3 (Bálint et al, 2014;Borschensky and Reinacher, 2014;Olasz et al, 2017b).…”

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confidence: 99%

Cellular localisation of the proteins of region 3 of feline enteric coronavirus

Mészáros

Olasz

Kádár-Hürkecz

et al. 2018

Acta Veterinaria Hungarica

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Feline enteric coronaviruses have three open reading frames (ORFs) in region 3 (3a, 3b, and 3c). All three ORFs were expressed with C-terminal eGFP and 3xFLAG tags in different cell lines and their localisation was determined. ORF 3a is predicted to contain DNA-binding and transcription activator domains, and it is localised in the nucleus and in the cytoplasm. ORF 3b is also predicted to contain DNA-binding and activator domains, and was found to localise in the mitochondrion. Besides that, in some of the non-infected and FIPV-infected cells nucleolar, perinuclear or nuclear membrane accumulation of the eGFP-tagged 3b was observed. The exact compartmental localisation of ORF 3c is yet to be determined. However, based on our co-localisation studies 3c does not seem to be localised in the ER-Golgi network, ERGIC or peroxisomes. The expression of 3c-eGFP is clearly cell type dependent, it is more stable in MARC 145 cells than in Fcwf-4 or CrFK cells, which might reflect in vivo stability differences of 3c in natural target cells (enterocytes vs. monocytes/macrophages).

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“…These reasons could explain the negative results in four cats (numbers 8,10,13,18) in which FCoV load was high in some samples, but FCoV with S gene mutations was not detected. Interestingly, although S gene mutation RT-PCR was negative despite a high virus load in one sample, FCoV with S gene mutation or mixed FCoV (both FCoVs with and without S gene mutations) were detected in at least one different tissue or fluid in all of the four cats.…”

Section: Discussionmentioning

confidence: 97%

“…27,33 Another reason could be the absence of the particular S gene mutations examined here and the presence of other mutations involved in FIP pathogenesis inst ead. 6,8,9,14,15,38,39 Some other mutations, such as in the 3c gene, have been discussed as playing a role in FIP pathogenesis, but a clear causal relationship to FIP still has not been identified. 6,7,40,41 Most likely, a combination of different mutations leads to the FCoV virulence change and, ultimately, to the development of FIP.…”

Section: Discussionmentioning

confidence: 99%

“…A combination of different mutations on different genes is likely as mutations that have been identified to date do not qualify as sole causes for FIP. [5][6][7][8] This results in FCoV strains with different genome sequences in each cat with FIP, 6,9,10 highlighting that there are multiple pseudo-strains of FCoV within an individual cat and that a single consistent mutation responsible for all cases of FIP does not exist. Following mutation, increased virulence of FCoV is the result of a change in viral cell tropism from enterocytes to macrophages and efficient replication within these cells.…”

Section: Introductionmentioning

confidence: 99%

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Feline coronavirus with and without spike gene mutations detected by real-time RT-PCRs in cats with feline infectious peritonitis

Emmler

Felten

Matiasek

et al. 2019

Journal of Feline Medicine and Surgery

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Objectives Feline infectious peritonitis (FIP) emerges when feline coronaviruses (FCoVs) mutate within their host to a highly virulent biotype and the immune response is not able to control the infection. FCoV spike (S) gene mutations are considered to contribute to the change in virulence by enabling FCoV infection of and replication in macrophages. This study investigated the presence of FCoV with and without S gene mutations in cats with FIP using two different real-time RT-PCRs on different samples obtained under clinical conditions. Methods Fine-needle aspirates (FNAs) and incisional biopsies (IBs) of popliteal and mesenteric lymph nodes, liver, spleen, omentum and kidneys (each n = 20), EDTA blood (n = 13), buffy coat smears (n = 13), serum (n = 11), effusion (n = 14), cerebrospinal fluid (n = 16), aqueous humour (n = 20) and peritoneal lavage (n = 6) were obtained from 20 cats with FIP diagnosed by immunohistochemistry. Samples were examined by RT-PCR targeting the FCoV 7b gene, detecting all FCoV, and S gene mutation RT-PCR targeting mutations in nucleotides 23531 and 23537. The prevalence of FCoV detected in each sample type was calculated. Results In 20/20 cats, FCoV with S gene mutations was present in at least one sample, but there was variation in which sample was positive. FCoV with mutations in the S gene were most frequently found in effusion (64%, 95% confidence interval [CI] 39-89), followed by spleen, omentum and kidney IBs (50%, 95% CI 28-72), mesenteric lymph node IBs and FNAs (45%, 95% CI 23-67), and FNAs of spleen and liver and liver IBs (40%, 95% CI 19-62). Conclusions and relevanceIn these 20 cats with FIP, FCoVs with S gene mutations were found in every cat in at least one tissue or fluid sample. This highlights the association between mutated S gene and systemic FCoV spread. Examining a combination of different samples increased the probability of finding FCoV with the mutated S gene.

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Mutations in the 3c and 7b genes of feline coronavirus in spontaneously affected FIP cats

Cited by 25 publications

References 41 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

Cellular localisation of the proteins of region 3 of feline enteric coronavirus

Feline coronavirus with and without spike gene mutations detected by real-time RT-PCRs in cats with feline infectious peritonitis

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