Rethinking the Drivers of Coronavirus Virulence and Pathogenesis: Toward an Understanding of the Dynamic World of Mutations, Indels, and Recombination Within the Species Alphacoronavirus-1 DOI Creative Commons
Ximena A. Olarte‐Castillo, Annette Choi, Laura E. Frazier

et al.

Published: Nov. 26, 2024

Alphacoronaviruses are widespread but understudied in comparison to betacoronaviruses. Recombination, mutations, and indels hallmarks of coronavirus replication, which together facilitate viral spillover emergence, especially within the alphacoronaviruses. The species _Alphacoronavirus-1_ comprises distinct viruses cats, dogs pigs. In high-pathogenicity feline (FCoV) is infamous as cause infectious peritonitis (FIP), a lethal disease that can now be treated with antiviral drugs. FCoV-1 exists two genotypes (type -1 -2) transmitted low-pathogenicity virus causes mild or asymptomatic disease. FCoV variants arise cats already infected FCoV, while mutations responsible for this phenotype change remain enigmatic, main determinant pathogenicity spike glycoprotein. outcome driven by combination both within- between-host evolution, whereas FCoV-2 appears recombination co-circulating canine coronaviruses (CCoV). virulence largely explained using “furin cleavage site (FCS) disruption hypothesis,” argues contains an intact FCS has disrupted unable cleaved. pathogenesis exemplified FCoV-23, novel canine/feline recombinant caused outbreak severe Cyprus during 2023. As such, _Alphacoronavirus-1 _mayexist adynamic "metavirome"1 constant state flux, presenting notable challenges surveillance management, risk-assessment.

Language: Английский

In Vitro Evaluation of Aryl Hydrocarbon Receptor Involvement in Feline Coronavirus Infection DOI Creative Commons

Luca Del Sorbo,

Rosa Giugliano,

Claudia Cerracchio

et al.

Viruses, Journal Year: 2025, Volume and Issue: 17(2), P. 227 - 227

Published: Feb. 6, 2025

Feline coronavirus (FCoV) is an alphacoronavirus (αCoV) that causes moderate or chronic asymptomatic infection in cats. However, a single infected cat, FCoV can modify its cellular tropism by acquiring the ability to infect macrophages, resulting development of feline infectious peritonitis (FIP). In this context, restrain impact infection, scientific research has focused attention on antiviral therapies involving novel mechanisms action. Recent studies have demonstrated aryl hydrocarbon receptor (AhR) signaling regulates host response different human and animal CoVs. Hence, mechanism action AhR was evaluated upon Crandell Kidney (CRFK) canine fibrosarcoma (A72) cells. Following with enteric CoV (FECV), strain "München", significant activation target CYP1A1, observed. The selective antagonist CH223191 provoked reduction replication levels viral nucleocapsid protein (NP). Furthermore, effect inhibitor acidity lysosomes cells Our findings indicate acts upregulates AhR. repressed virus yield through inhibition respect, for counteracting FCoV, represents new useful identifying drugs. Moreover, presence CH223191, alkalinization FCoV-infected CRFK detected, outlining their involvement activity.

Language: Английский

Citations

1
Study of key residues in MERS-CoV and SARS-CoV-2 main proteases for resistance against clinically applied inhibitors nirmatrelvir and ensitrelvir DOI Creative Commons
Laura Krismer, Helge Schöppe, Stefanie Rauch

et al.

npj Viruses, Journal Year: 2024, Volume and Issue: 2(1)

Published: June 24, 2024

Abstract The Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is an epidemic, zoonotically emerging pathogen initially reported in Saudi Arabia 2012. MERS-CoV has the potential to mutate or recombine with other coronaviruses, thus acquiring ability efficiently spread among humans and become pandemic. Its high mortality rate of up 35% absence effective targeted therapies call for development antiviral drugs this pathogen. Since beginning SARS-CoV-2 pandemic, extensive research focused on identifying protease inhibitors treatment SARS-CoV-2. Our intention was therefore assess whether these are viable options combating MERS-CoV. To that end, we used previously established assays quantify inhibition SARS-CoV-2, main proteases. Nirmatrelvir inhibited several proteases, whereas ensitrelvir less broadly active. simulate nirmatrelvir’s clinical use against subsequent resistance development, applied a safe, surrogate virus-based system. Using virus, selected hallmark mutations SARS-CoV-2-M pro , such as T21I, M49L, S144A, E166A/K/V L167F. In current study, pool MERS-CoV-M mutants, characterized modelled steric effect catalytic site mutants S142G, S142R, S147Y A171S.

Language: Английский

Citations

6
Molecular detection using hybridization capture and next-generation sequencing reveals cross-species transmission of feline coronavirus type-1 between a domestic cat and a captive wild felid DOI Creative Commons
Ximena A. Olarte‐Castillo, Laura B. Goodman, Gary R. Whittaker

et al.

Microbiology Spectrum, Journal Year: 2024, Volume and Issue: 12(10)

Published: Aug. 19, 2024

ABSTRACT Feline coronavirus (FCoV) infection normally causes mild or subclinical signs and is common in domestic cats. However, some cats, FCoV can also lead to the development of feline infectious peritonitis (FIP)—a typically lethal disease. has two serotypes genotypes, FCoV-1 FCoV-2, both which cause FIP. The main difference between genotypes viral spike (S) protein that determines tropism pathogenicity, crucial mechanisms Subclinical FIP have been reported wild felids, including threatened species. Due high genetic variability S gene technical challenges sequencing it, detection characterization felids mainly centered on other more conserved genes. Therefore, genotype causing most remains unknown. Here, we report a retrospective molecular epidemiological investigation zoological institution U.Ss. In 2008, cat ( Felis catus ) Pallas’ Otocolobus manul sharing same room succumbed Using situ hybridization, detected RNA different tissues felids. hybridization capture next-generation sequencing, detected, sequenced, characterized whole genome infecting Our data show for first time be transmitted extends known host range FCoV-1. findings highlight importance identifying FIP, develop effective control measures. IMPORTANCE highly prevalent cats worldwide endangered species, it caused substantial population declines. Characterizing diversity due recent reports novel pathogenic recombinant variants mortality feral Cyprus. this epidemiology study, used archived samples collected U.S. felid FCoV. (HC) naturally We demonstrate efficacy HC detecting FCoV, essential characterize its genotypes.

Language: Английский

Citations

4
Hopf bifurcation in the shadow of extinction: Collaborating with epidemic dynamics through lethal mutations and declining ancestor infections DOI
Ali Demırcı, Ayşe Hümeyra Bilge, Cihangir Özemir

et al.

Biosystems, Journal Year: 2025, Volume and Issue: 248, P. 105406 - 105406

Published: Feb. 1, 2025

Language: Английский

Citations

0
An outbreak of canine coronavirus type 2 in captive snow leopards (Panthera uncia) demonstrates a possible role for felids as mixing vessels for alphacoronaviruses DOI Creative Commons
Ximena A. Olarte‐Castillo,

Abigail B. Schlecht,

Paul P. Calle

et al.

IJID One Health, Journal Year: 2025, Volume and Issue: unknown, P. 100057 - 100057

Published: March 1, 2025

Language: Английский

Citations

0
Application of versatile reverse genetics system for feline coronavirus DOI Creative Commons
Izumi Kida, Tomokazu Tamura, Yudai Kuroda

et al.

Microbiology Spectrum, Journal Year: 2025, Volume and Issue: unknown

Published: March 10, 2025

ABSTRACT Feline infectious peritonitis (FIP) is a fatal disease caused by feline coronavirus (FCoV). Although multiple gene mutations in FCoV likely account for FIP pathogenesis, molecular studies have been limited due to the lack of suitable reverse genetics system. In present study, we established rapid PCR-based system generate recombinant using circular polymerase extension reaction (CPER) method both serotype 1 and 2 viruses. Recombinant was successfully rescued at sufficient titers propagate progeny viruses with high sequence accuracy. The growth kinetics were comparable those parental We generated recombinants harboring spike from different strain or reporter HiBiT tag CPER method. chimeric virus demonstrated similar characteristics gene. stably expressed after five serial passages susceptible cells, could be applied evaluate sensitivity antiviral inhibitors luciferase assay detect tag. Taken together, our versatile shown herein robust tool characterize viral genes even without isolation investigate mechanisms proliferation pathogenicity FCoV. IMPORTANCE highly cats variants that can infect systemically. Due toolbox manipulating genome, an efficient urgently needed study proteins responsible severe disease. Herein, capability introduced desired modifications any negative impacts on cell culture. are also useful efficacy. Overall, promising reveal life cycle progression peritonitis.

Language: Английский

Citations

0
Die feline infektiöse Peritonitis – ein aktueller Überblick DOI
Katharina Zwicklbauer, Michèle Bergmann, Martin Alberer

et al.

Tierärztliche Praxis Ausgabe K Kleintiere / Heimtiere, Journal Year: 2025, Volume and Issue: 53(02), P. 96 - 102

Published: April 1, 2025

Zusammenfassung Coronaviren (CoVs) sind positiv einzelsträngige RNA-Viren, die verschiedene Tierarten sowie Menschen infizieren können. Besonders relevant für Katzen ist das feline Coronavirus (FCoV), in Katzenpopulationen weltweit verbreitet ist. Eine Infektion mit FCoV verläuft der Regel ohne Symptome. In Mehrkatzenhaushalten entwickeln jedoch etwa 5–12% FCoV-infizierten aufgrund von Mutationen im Spike-Gen infektiöse Peritonitis (FIP). FIP eine immunvermittelte Erkrankung, bislang immer tödlich verlief. Die führen zu einem Tropismus-Wechsel Enterozyten Monozyten und Makrophagen. Der damit verbundene Wechsel Virulenz führt charakteristischen granulomatösen Vaskulitis Perivaskulitis, bei beobachtet wird. letzter Zeit gibt es zahlreiche neue Erkenntnisse zur FIP. So zeigen Studien, dass humanmedizinische antivirale Medikamente, wie Nukleosidanalogon GS-441524, wirksam betroffenen Überlebenschance bis 100% bieten. Zudem wurde neuartige FCoV-Variante, FCoV-23, aus Zypern identifiziert. Dieses Virus entstand nach derzeitigem Kenntnisstand durch Rekombination zwischen dem hochvirulenten pantropischen caninen Coronavirus; kann direkt Katze übertragen werden auslösen. Darüber hinaus mehr Hinweise darauf, häufig einer Myokarditis assoziiert Dieser Artikel bietet einen Überblick über den aktuellen Wissensstand FIP, unter Berücksichtigung Pathologie, klinischer Symptome, wirksamer Therapiemöglichkeiten Präventionsmaßnahmen.

Citations

0
Rapid Clinical Resolution and Differential Diagnosis of a Neurological Case of Feline Infectious Peritonitis (FIP) Using GS-441524 DOI Creative Commons
Huong Huynh,

Pamela Moraguez,

Logan M. Watkins

et al.

Pathogens, Journal Year: 2025, Volume and Issue: 14(5), P. 424 - 424

Published: April 27, 2025

Case summary: A 2-year-old male neutered domestic shorthair cat was presented with a progressive history of tetraparesis, ataxia, and inappetence over 4 days. physical exam revealed mucopurulent nasal discharge stertor. neurologic multifocal neurolocalization. The non-ambulatory tetraparetic developed seizures while in hospital. Hematologic assessment anemia, hypoalbuminemia hyperglobulinemia. Magnetic resonance imaging (MRI) the brain meningeal contrast enhancement brainstem cervical spine, as well mandibular retropharyngeal lymphadenopathy. Cerebrospinal fluid marked neutrophilic pleocytosis; no infectious organisms were seen. Toxoplasma IgG/IgM Cryptococcus antigen latex agglutination negative. Mandibular abdominal lymph nodes aspirated, cytology mixed inflammation. suspected to have feline peritonitis, aid clinical diagnosis he enrolled research study—with targeted Nanopore-based sequencing specifically identifying characterizing FCoV-1 RNA spinal anal swab, but not urine. treated anticonvulsants (phenobarbital levetiracetam), an antibiotic (ampicillin/clavulanic acid), GS-441524. Neurologic signs did improve on alone improved significantly after two subcutaneous injections received 84-day course GS-441524 and, at time manuscript preparation (over 12 months diagnosis), remains ambulatory seizure-free without recurrence detectable viral shedding feces.

Language: Английский

Citations

0
FCoV‐23 causing FIP in a cat imported to the UK from Cyprus DOI
Amanda Warr, Charalampos Attipa, Danièlle Gunn‐Moore

et al.

Veterinary Record, Journal Year: 2023, Volume and Issue: 193(10), P. 414 - 415

Published: Nov. 17, 2023

cat imported to the UK from Cyprus

Language: Английский

Citations

6
Cellular dynamics shape recombination frequency in coronaviruses DOI Creative Commons
Cassandra M. Bonavita, Heather Wells, Simon J. Anthony

et al.

PLoS Pathogens, Journal Year: 2024, Volume and Issue: 20(9), P. e1012596 - e1012596

Published: Sept. 27, 2024

Coronavirus genomes have evolutionary histories shaped extensively by recombination. Yet, how often recombination occurs at a cellular level, or the factors that regulate rates, are poorly understood. Utilizing experimental co-infections with pairs of genetically distinct coronaviruses, we found is both frequent and rare during coinfection. Recombination occurred in every instance co-infection yet resulted relatively few recombinant RNAs. By integrating discrete-time Susceptible-Infected-Removed (SIR) model, rates determined primarily co-infection, rather than other possible barriers such as RNA compartmentalization. staggering order timing infection each virus also themselves heavily influenced genetic ecological mechanisms, including superinfection exclusion relative fitness competing viruses. Our study highlights potent regulated force: enough to ensure steady influx mutations but infrequent maintain genomic integrity. As thought be an important driver host-switching disease emergence, our provides new insights into coronavirus evolution more broadly.

Language: Английский

Citations

2