Feline Coronavirus (FCoV) is an RNA virus that is infectious for cats. It has two different forms; the FECV (Feline Enteric Coronavirus) that infects the intestines and the FIPV (Feline Infectious Peritonitis Virus) that causes the disease Feline infectious peritonitis. This virus is part of the coronavirus group 1, which includes the porcine gastroenteritis swine coronavirus (TGEV), the canine coronavirus (CCOV) and some human coronavirus.
The digestive form of FECV
FECV virus is responsible for an infection of the gastrointestinal epithelial cells (see also enterocytes, brush border, microvilli, villi). This intestinal infection has few outward signs, and is usually chronic. The virus is excreted in the feces of the healthy carrier, and can be detected by Polymerase Chain Reaction or "PCR" of feces or by PCR testing of rectal samples.
Cats living in groups can contaminate each other during visits to a communal litter tray. Some cats are resistant to the virus and can avoid infection or even becoming carriers, while others may become FECV carriers. Carriers may heal spontaneously, but acquired immunity may be short and they may go on to reinfect, usually within a few weeks, if they are living in a group with healthy, but persistent excretory carriers. Some cats never heal and the excretory phase remains permanently.
Mutation from the FECV form to FIPV
Random errors can occur in the virus infecting an enterocyte causing the virus to mutate from FECV to FIPV.
In a large group of cats (n) the epidemiological risk of mutation (E) is higher:
E = (n ²)-n
A house hosting 2 cats therefore has a mutation risk = 2. when 4 kittens born into this house, the risk goes up from 2 to 30.
Cats visiting communal litter trays can be permanently infected with a larger number of different strains of virus.
In their pre-domestication natural state cats were solitary animals and didn't share their areas (hunting areas, rest areas, defecation sites, etc.). Domestic cats living in a group create a much higher epidemiological risk situation.
After this mutation, the FCoV acquires a tropism for macrophages  (see also: Immune cells, leucocyte, monocyte, dendritic cells, mononuclear cell, antigen-presenting cell) while losing intestinal tropism.
Feline infectious peritonitis and the FIPV virus
See also the special article about feline infectious peritonitis
In a cat group, overcrowding increases the risk of mutation and conversion (from FECV to FIPV) and constitutes a major risk factor for the development of feline infectious peritonitis(FIP) cases. FIP will mainly develop in cats whose immunity is low; such as younger kittens, old cats, immunosuppression due to viral — FIV (Feline immunodeficiency virus) and / or FeLV Feline leukemia virus and stress, including the stress of separation and adoption.
Infection of macrophages by FIPV is responsible for development of a fatal granulomatous vasculitis, or FIP (see granuloma).
Therefore, FIP occurs when 2 factors are present: (virus mutation) AND (cat health status)
- Virus mutation: this virological factor depends of the replication level.
- Immune status of each cat, which is related to the age, the genetic pool and the stress level : the more the immune status is good, the more the virus is slowed down.
2 different clinical forms of FIP '(feline infectious peritonitis )':
- An effusive form with effusion peritoneal fluid (= ascites), pleural and pericardial,
- And a dry form.
The outcome is usually fatal, but a few cases of healing, with feline omega interferon treatment, have been reported.
Molecular aspects of virus fusion to the host cell
The 2 different forms of FCoV, enteric (FECV) and FIP (FIPV), get 2 different serotypes along with different antigens resulting in production of different antibodies: serotype.
The FCoV serotype I (also called Type I) is most frequent; 80% of infections are due to type I FECV that could mutate to FIPV type I. Serotype I FCoV cultures are difficult to perform, with few resulting studies.
The FCoV serotype II (also called type II) is less frequent: FECV type II that can mutate to FIPV type II. FCoV type II is a recombinant virus type I with spike genes (S protein) replacement from FCoV by the canine enteric coronavirus (CCOV) spikes. The type II cultures are easier to perform, so we have got many studies about type II (though it is less common form).
Model: "data about FCoV type II"
FCoV is an RNA viruses that is included in the coronaviruses group 1. Coronaviruses are covered with several types of proteins "S proteins" (or E2) forming a crown of protein spikes to the virus surface. Coronaviruses take their name from the observation of this crown by electron microscopy
These spikes of Cov (group 1 and serotype II) are responsible for the infection power of the virus by binding the virus particle to a membrane receptor of the host cell: the Feline Amino peptidase N (fAPN).
fAPN (feline), hAPN (human) and pAPN (porcine) differ in some areas of N-glycosylation, therefore:
- All strains of the coronavirus study group 1 (feline, porcine and human) can bind to the feline aminopeptidase N fapn but:
- The human coronavirus can bind to the human APN (HAPN) but not to the porcine type receptor (pAPN)
- The pig coronavirus can bind to the porcine APN (pAPN) but not the human type receptor (hAPN).
At the cellular level this explains why the glycosylation level of enterocytes APN is important for the binding of virus to the receptor. 
The FECV spikes have a high affinity for enterocytes fAPN, while the mutant FIPV spikes have a high affinity for the macrophages fAPN.
During the viral replication cycle, spikes proteins mature in the host cell Golgi complex with a high mannose glycosylation.
This spike manno-glycosylation stage is indispensable for the acquisition of coronavirus virility. 
Data about FCoV type I
In 2007, it was well established that serotype I did not work with the FCoV fapn receptor. The FCoV type I receptor still is unknown.
News about CoV receptor
ACE and DC-SIGN are two trans-membrane receptors (mannose receptors) which can bind 'the plant lectins C-type mannose binding'. DC-SIGN and ACE serve as retrovirus receptors.
- Aminopeptidase N has the same ability to interact with plant lectins C-type mannose-binding and also serves as a receptor for a retrovirus.
- Angiotensin-converting enzyme ACE, aminopetidase A and aminopeptidase N have cascading actions in the renin-angiotensin-aldosterone system, which suggests a common phylogenetic origin between these molecules.
- Some advanced studies have shown a high homology between the Aminopeptidase N and the Angiotensin-converting enzyme.
- It is likely that the unknown FCoV serotype I receptor is also of this receptor family and acts with mannose binding lectins.
Role of mucus and glycocalix — Interactions between viruses and sialic acid
Sialic acid is a component of the complex sugar glycocalix, i.e. mucus protecting the gastrointestinal and respiratory mucosa. Sialic acid is an important facilitating fusion factor of any viruses to its host cell. This has been very well studied for flu.
Extensive data also shows that processes using sialic acid are directly involved in the interaction with receptor's lectins.
It has been demonstrated that swine enteric coronavirus (group 1) fusion to the enterocyte was through binding to the APN in the presence of sialic acid, 2 elements are necessary.
About Felin coronavirus infections, it seems that the infection is sialic acid dependent.
Inhibition of the fusion: some studies (in vitro)
To inhibit the fusion of the virus to the cell, several solutions are possible:
- modify glycosylation level of the viral spikes,
- Change the level of glycosylation of fAPN,
- Compete with the spikes, with molecules that will bind to fapn (occupation of the binding site),
- Inhibit the binding depends on the sialic acid mucus.
- Experimentally the binding of FIPV (spike) in macrophages (fapn) is strongly inhibited by mannan(s)( mannose complex sugar — see also, glycan, manno-oligosaccharide, MOS oligosaccharide): that compete with the fapn. With mannose, the inhibition is less than with Mannan-oligosaccharides.
- Some Molecules can inhibit glycosylation of spikes (monensin, tunicamycin ...) reduce or cancel the virus infesting power (action in the Golgi. The same is true for mannanases and mannosidase enzymes that cut mannose out of the spikes.
- The competition with spikes by other molecules having an affinity for fapn '(common sugar recognition process)' cancel or reduce the power of infesting CoV:
- Mannan binding Lectin:
- Allium agglutinins
- Urtica dioica agglutinins
- Pradamycine A .../...
- Collectine .../...
-Manno-Oligosaccharides (MOS) : source: yeast
- sialic acid :
Experimental sialic acid inhibition can decrease the avian and human coronavirus infectivity.
Protecting kittens through breastmilk
Kittens born from mothers carrying FECV are protected from infection during their first weeks of life until weaned by maternal antibodies. Diane D. Addie advocates early weaning and segregation of kittens from their mother before they contaminate each other (at about 5 to 6 weeks). Kittens with no outside contamination and that are deprived of contact with their mother during their first 2 months of life (an important immunological period) may be protected.
The initial protection of the kittens is very effective. We have to reflect about the different possible ways to do it.
It is widely accepted that passive protection is passed on to kittens by immunoglobulins nursery (antibodies) provided by colostrum and milk from the mother.
Several questions arise:
- If this protection is only supported by maternal antibodies, why don't these antibodies protect the mother herself?
- If the kittens born to a mother's blood group B are removed from their mother for 24 hours (to avoid Hemolytic disease of the newborn) and thus have no systemic passage of maternal antibodies, why don't we see FCoV infection in these kittens more often than others?
Other molecules from colostrum and cat milk, could also bear this coverage:
Lactoferrin has many properties that make it a very good candidate for this anti-coronavirus activity:
- As CoV group I, it binds to APN 
- As the SARS CoV, it binds to enzymes convert angiotensin
- It binds to DC-SIGN of macrophage,
- The Lactoferrin anti-viral activity is sialic acid dependent.
The structures of the polypeptide chain and carbohydrate moieties of bovine lactoferrin (bLF) are well established. bLF consists of a 689-amino acid polypeptide chain to which complex and high-mannose-type glycans are linked (Pierce et al., 1991)
The colostrum and breast milk also contains:
- Many oligosaccharides (glycan) responsible for anti-viral,
- Many maternal immune cells,
- Many cytokines (interferon ...); whose role by oro-mucosal route seems very important.
- sialic acid: during lactation, it appears that neutralizing oligo-saccharides binding sialic acid decreases when it binds increasingly to glycoproteins. (The APN is a glycoprotein). The anti-viral effect of lactoferrin is increased by the removal of sialic acid.
- Mannan binding lectins.
Other protective factors
Other assumptions may help to explain this resistance to FCoV infections by kittens.
- In the first weeks of life, APN could be immature because highly manno-glycosylated. The spikes of CoV could then not be bound.
- Factors in breastmilk may inhibit the synthesis of fANP by enterocytes, as already described with fructose or sucrose.
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