Abstract
Feline infectious peritonitis (FIP) is a fatal feline immune-mediated disease caused by feline infectious peritonitis virus (FIPV). Little is known about the biological pathways associated in FIP pathogenesis. This is the first study aiming to determine the phenotypic characteristics on the cellular level in relation to specific metabolic pathways of importance to FIP pathogenesis. Methods: The internalization of type II FIPV WSU 79-1146 in Crandell-Rees Feline Kidney (CrFK) cells was visualized using a fluorescence microscope, and optimization prior to phenotype microarray (PM) study was performed. Then, four types of Biolog Phenotype MicroArray™ plates (PM-M1 to PM-M4) precoated with different carbon and nitrogen sources were used to determine the metabolic profiles in FIPV-infected cells. Results: The utilization of palatinose was significantly low in FIPV-infected cells; however, there were significant increases in utilizing melibionic acid, L-glutamine, L-glutamic acid and alanyl-glutamine (Ala-Gln) compared to non-infected cells. Conclusion: This study has provided the first insights into the metabolic profiling of a feline coronavirus infection in vitro using PMs and deduced that glutamine metabolism is one of the essential metabolic pathways for FIPV infection and replication. Further studies are necessary to develop strategies to target the glutamine metabolic pathway in FIPV infection.
Highlights
The recent worldwide outbreak of a novel coronavirus, namely coronavirus disease 2019(COVID-19), and the sudden emergence of coronavirus-related diseases in past decades has greatly attracted the attention of researchers in uncovering the pathophysiology and pathogenesis of coronaviruses to expedite the progress in finding effective antiviral treatments [1,2]
This study has provided the first insights into the metabolic profiling of a feline coronavirus infection in vitro using phenotype microarray (PM) and deduced that glutamine metabolism is one of the essential metabolic pathways for feline infectious peritonitis virus (FIPV) infection and replication
At 1 hpi, fluorescein isothiocynate (FITC)-conjugated antibody targeting the nucleocapsid of FIPV was detected at a very low intensity, which indicated that the entry of the virus into the cells was at the early stage
Summary
The recent worldwide outbreak of a novel coronavirus, namely coronavirus disease 2019(COVID-19), and the sudden emergence of coronavirus-related diseases in past decades has greatly attracted the attention of researchers in uncovering the pathophysiology and pathogenesis of coronaviruses to expedite the progress in finding effective antiviral treatments [1,2]. Coronaviruses are enveloped, single-stranded, positive-sense RNA viruses and differentiated into four groups based on their genetic and serological properties, and these viruses are known to cause acute and chronic respiratory disease, central nervous system disease and gastroenteritis in animals and human [2]. Feline coronavirus (FCoV) is an omnipresent virus that infects cats and is primarily transmitted through. FCoV is characterized as an Alpha-coronavirus—a category in which transmissible gastroenteritis virus and human coronavirus 229E (HCoV-229E) are grouped [3]. FCoV consists of two different biotypes: feline enteric coronavirus (FECV) and feline infectious peritonitis virus (FIPV). Cats infected with FECV usually are asymptomatic or sometimes with mild enteritis (self-limiting diarrhoea), while FIPV causes a lethal immune-mediated feline disease which is feline infectious peritonitis (FIP) [4]. FCoV consists of two serotypes: type I FCoV and type II FCoV
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