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Feline coronavirus

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Feline coronavirus FCoV

It is an RNA virus that can infect cats. This virus has 2 forms:

1/ An enteric one (intestinal) called FECV (Feline Enteric Coronavirus)

2/ And a form that can cause the feline infectious peritonitis FIPV (Feline infectious peritonitis virus).

They are part of the coronavirus group 1, like the porcine gastroenteritis swine coronavirus (TGEV), the canine coronavirus (CCOV) and some human coronavirus.

The cat coronavirosis

The digestive form FECV

FECV virus is responsible for an infection of the gastrointestinal epithelial cells of the cat (the intestinal lining cells) See also enterocytes, brush border, microvilli, villi ...): intestinal infection with few signs, it is most often chronic. The virus is then excreted in the feces of the animal (healthy carrier). This port can be demonstrated by rectal sampling (swab) and detection by PCR: Polylmerase Chain Reaction or "PCR".

Cats living in groups are contaminating each other during visits to the litter tray. Some cats are resistant to the virus and have no infection (no carrying digestive). Others will be carriers of FECV some time. They may heal spontaneously, but acquired immunity is short, they are going to infect an other time during a few weeks if they are living in a group with persistent excretory (healthy carriers). Some cats never heal and excretory remain permanently.

Passage from the FECV form to the FIPV one

Random errors replication in the enterocyte, sometimes the virus can mutate from FECV to FIPV.

More the cat group is big (n cats) and more the epidemiological risk of mutation (E) is high:

E = (n ²)-n

A house hosting 2 cats has a mutation risk = 2. If 4 kittens born in this house, the risk growth up from 2 to 34.

It's easy to understand, cats are permanently infected with a larger number of different strains of virus (as different from cats), visiting litter tray.

In the natural state cats are solitary animals, they don't sharing their areas (hunting area, rest area, area of defecation ...). Often domestic cats live in a group, it's a hight epidemiological risk situation.

After mutaion, the FCoV acquires a tropism for the macrophages [1] (see also: Immune cells, white blood cell, leucocyte monocyte, dendritic cells, mononuclear cells, antigen presenting cell ...) while losing the intestinal tropism.

The feline infectious peritonitis and the FIPV virus

See also the special article about feline infectious peritonitis

In a cat group, the overcrowding and the risk of mutation (from FECV to FIPV) are risk factors for the development of cases of feline infectious peritonitis '(FIP)' . However, the FIP will mainly develop in cats whose immunity is low (younger kittens, old cats, immunosuppression due to viral - FIV (Immunodefience feline) and / or FeLV (virus the Feline leukosis) - stress including stress of separation and adoption).

Infection of macrophages by FIPV is responsible for a fatal granulomatous vasculitis, the FIP (see granuloma).

Therefore, FIP can occur in 2 factors are meeting: (virus mutation) AND (cat field)

  • Mutation of the virus: virological factor related to the number of replication ...
  • Field of cats related to its age, its genetics, its stress level, which determines the immune status and thus its ability (or not) to contain the infection at a low level.


There are 2 clinical forms of FIP '(feline infectious peritonitis )':

  1. An effusive form with effusion peritoneal fluid (= ascites), pleural and pericardial,
  2. And a dry form.

Usually, the outcome is fatal, except for a few reported cases of healing with the feline omega interferon treatment.


Molecular aspects of the virus fusion to the host cell

The 2 forms of FCoV, the enteric one (FECV) and the FIP one (FIPV) have both from 2 different serotypes (with different antigens that cause different antibodies production of: 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 FCover Cultures are not easy, so studies about this serotype are few.


The FCoV serotype II (also called type II) are less frequent: FECV type II that can mutate to FIPV type II. FCoV type II is a recombinant virus type I with spikes genes (S protein) replacement from FCoV by the canine enteric coronavirus (CCOV)spikes. [2] The type II cultures are easier, so we have many studies about this type II (though less common).

Model: "FCoV data about type II"

Virus fusion

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 Spike 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 him to a membrane receptor of the host cell: the Feline Amino peptidase N (fAPN). [3] · [4] · [5]

The viral receptor: aminopeptidase N (APN )

fAPN (feline), hAPN (human) and pAPN (porcine) differ in some areas of N-glycosylation, that can explain:

  • 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 form receptor (pAPN)
  • The pig coronavirus can bind to the porcine APN (pAPN) but not the human form receptor (hAPN).

At the cellular level this facts can explain why the glycosylation level of enterocytes APN is important for the binding of virus to the receptor. [6] · [7]

About viral spikes

The FECV spikes have a high affinity for enterocytes fAPN , while the mutant FIPV spikes have a high affinity for the macrophages ones.

During the viral replication cycle, spikes proteins have a maturation in the host cell golgi with a high mannose glycosylation.

This spike manno-glycosylation stage is indispensable for the acquisition of coronavirus infesting power. [8] · [9]

FCoV data about type I

The receptor?

In 2007, it is well established that serotype I do not work with the FCoV fapn receptor. The FCoV type I receptor still is unknown.[10]


News about CoV receptor

  • The human CoV SARS binds to the enzyme angiotensin converting ACE II. The ACE II is also called 'L-SIGN'.
  • Coronaviruses bind to macrophages via the "DC-SIGN". Sign-DC = Dendritic cell (see also hepatitis C, hepatitis B, HIV ...)

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.[11]


  • Aminopeptidase N has the same ability to interact with plant lectins C-type mannose binding and also serves as a receptor for a retrovirus.
  • Converting enzyme ACE, aminopetidase A and aminopeptidase N have cascading actions in the renin-angiotensin-aldosterone system[1], wich is suggesting a common phylogenetic origin between these molecules.
  • Some advanced studies have shown a high homology between the N and Aminopeptidase enzyme angiotensin converting.[12]


  • It is likely that the unknown FCoV serotype I receptor is also of this receptor family that acting with the mannose binding lectins.

Role of mucus and glycocalix - Interactions between viruses and sialic acid

Sialic acid is a component of the complex sugar glycocalix, ie mucus protecting the gastrointestinal mucosa (but also respiratory one...). Sialic acid is an important facilitating fusion factor of any viruses to the host cell. This is very well detailed for the flu.

Extensive data also show that processes using sialic acid are directly involved in the interaction with receptors lectins.[13]


About swine enteric coronavirus (group 1), it has been demonstrated that fusion to the enterocyte was through binding to the APN in the presence of sialic acid, the 2 elements are necessary. [14] · [15] · [16]

About Felin coronavirus infections, it seems that the infection is sialic acid dependent.[17] · [18]

Inhibition de la fusion : quelques études (in vitro)

Pour inhiber la fusion du virus à la cellule, plusieurs solutions sont possible :

  1. déglycosyler les spikes viraux,
  2. modifier le niveau de glycosylation de l'fAPN,
  3. entrer en compétition avec les spikes, grâce à des molécules qui vont se lier aux fAPN (occupation du site de liaison),
  4. inhiber la liaison dépendant de l'acide sialique du mucus.


  • Expérimentalement la liaison du FIPV (spike) aux macrophages (fAPN) est fortement inhibé par le(s) mannane(s) (sucre complexe composé de plusieurs molécules de mannose - voire aussi polyoside, glycan, manno-oligosaccharide, MOS, oligosaccharide) : effet de compétition avec la fAPN. L'inhibition est beaucoup moins importante avec le mannose qu'avec les oligosaccharides de mannose (mannanes).
  • Les molécules inhibant la glycosylation des spikes (Monensine, Tunicamycine …) diminuent ou annulent le pouvoir infestant du CoV (action au niveau de l'appareil de Golgi): non glycosylation des spikes. Il en est de même pour les mannanases (ou mannosidase = enzymes) déglycosylant le mannose les spikes.
  • La mise en compétition des spikes par d’autres molécules ayant une affinité pour fAPN (common sugar recognition process) diminuent ou annulent le pouvoir infestant du CoV :

- Lectine liée au mannose (Mannan binding Lectin) :

    • Lectine végétale (plant Lectin)[19]
  1. Allium agglutinines
  2. Urtica dioica agglutinines
  3. Pradamycine A .../...
    • Lectine animale et humorale (humoral lectin)
  1. Ficoline
  2. Collectine .../...

-Manno-Oligosaccharides (MOS) :

en quantité abondante dans les parois de levures (saccharomyces cerevisiae = levure de bière ou levure de boulanger)

- Acide sialique :

L'inhibition de l'acide sialique diminue le pouvoir infectant des coronavirus aviaires et humains. [20]

Protection des chatons par le lait maternel

Les chatons nés d’une mère porteuse du FECV sont protégés de l’infection pendant leurs premières semaines de vie (jusqu'à leur sevrage alimentaire). Le Dr. Addie [2] préconise un sevrage précoce et une séparation des chatons de leur mère avant que ces derniers ne se contaminent (5 à 6 semaines). Les chatons échappent à la contamination, mais sont alors privés du contact de leur mère durant leur 2° mois de vie (importante période éducative).

Cette protection initiale des chatons est si efficace qu'elle nous donne à réfléchir.

Les immunoglobulines

Il est communément admis que cette protection passive est supportée par les immunoglobulines maternelles (anticorps) transmises par le colostrum et la lait de la chatte.

Plusieurs questions se posent :

  1. Si cette protection n'est supportée que pas les anticorps maternels alors pourquoi ces mêmes anticorps ne protègent-ils pas mieux la mère?
  2. Les chatons nés d'une mère du groupe sanguin B sont retirés de leur mère pendant 24 heurs (afin d'éviter l'érythrolyse) et n'ont donc pas le passage systémiques des anticorps maternels. Pourquoi n'est il pas décrit d'infection à FCoV chez ces chatons plus que chez d'autres?

Le colostrum

D’autres molécules du colostrum et du lait de la chatte, doivent supporter également cette protection :

  • Lactoferrine,
  • Lactoperoxidase,
  • Lysozyme,
  • Polypeptide riche en Proline – PRP,
  • alpha-lactalbumine,
  • .../...

La lactoferrine présente de nombreuses propriétés qui en font un très bon candidat à cette protection anti-coronavirus :

  1. Comme les CoV du groupe I, elle se lie aux APN,[21]
  2. Comme le CoV du SRAS, elle se lie aux enzymes de conversions de l'angiotensine,[22]
  3. Elle se lie au DC-sign des macrophage,[23]
  4. Son activité anti-virale est dépendante de l'acide sialique.


Autres composants

Le colostrum et le lait maternelle contiennent également :

  1. de nombreux oligosaccharides (glycan) responsables d’une protection anti-virale,[24]
  2. des cellules immunitaires maternelles,
  3. des cytokines (interferon ...); dont le rôle par voie oro-mucosale semble très important.[25] · [26] · [27]
  4. de l'Acide sialique. Au cours de la lactation, il apparait que la liaison neutralisante de l'acide sialique aux oligo-saccharides diminue alors qu'il se lie de plus en plus aux glycoprotéines[28]. (La APN est une glycoprotéine). L'effet anti-viral de la Lactoferrine est augmenté par la suppression de l'acide sialique. [29]
  5. des Lectines liées au mannose. [30]
  6. .../...

Autres facteurs protecteurs

D'autres hypothèses peuvent contribuer à expliquer cette résistance des chatons au FCoV.

  • Dans les premières semaines de vie, les ANP pourraient être immatures car hautement manno-glycosylée.[31] Les spikes du CoV ne pourraient alors pas s'y lier.
  • Des facteurs du lait maternel pourraient inhiber la synthèse de l'fANP par les entérocytes, comme cela est déjà décrit avec le fructose ou le sucrose.[32] · [33] · [34]

Liens externes

[3] Sites du Dr ADDIE qui se consacre la recherche sur la PIF

References

  1. ^ . Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum ((lang | en | Acquisition of macrophage tropism during the pathogenesis of feline infectious peritonitis is determined by mutations in the feline coronavirus spike protein }}
  2. ^ gov/pubmed/9557750? ordinalpos = 2 & itool EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum = ((lang | en | Feline coronavirus type II strains 79-1683 and 79-1146 originate from a double recombination between feline coronavirus type I and canine coronavirus .}}
  3. ^ Feline aminopeptidase N is a receptor for all group I coronaviruses
  4. ^ Feline aminopeptidase N serves as a receptor for feline, canine, porcine, and human coronaviruses in serogroup I
  5. ^ Virus-receptor interactions in the enteric tract. Virus-receptor interactions
  6. ^ Molecular determinants of species specificity in the coronavirus receptor aminopeptidase N (CD13): influence of N-linked glycosylation.
  7. ^ Identification of sugar residues involved in the binding of TGEV to porcine brush border membranes
  8. ^ Acquisition of macrophage tropism during the pathogenesis of feline infectious peritonitis is determined by mutations in the feline coronavirus spike protein.
  9. ^ Utilization of DC-SIGN for entry of feline coronaviruses into host cells.
  10. ^ Type I feline coronavirus spike glycoprotein fails to recognize aminopeptidase N as a functional receptor on feline cell lines
  11. ^ The C type lectins DC-SIGN and L-SIGN: receptors for viral glycoproteins.
  12. ^ Analyse structurale du site actif de trois métallopeptidases à zinc: Endopeptidase Neutre-24. II, Aminopeptidase N et Enzyme de Conversion de l'Angiotensine
  13. ^ Sialic acid-specific lectins: occurrence, specificity and function.
  14. ^ Binding of transmissible gastroenteritis coronavirus to cell surface sialoglycoproteins.
  15. ^ Identification of sugar residues involved in the binding of TGEV to porcine brush border membranes.
  16. ^ Binding of transmissible gastroenteritis coronavirus to brush border membrane sialoglycoproteins.
  17. ^ Association between faecal shedding of feline coronavirus and serum alpha1-acid glycoprotein sialylation.
  18. ^ Serum alpha1-acid glycoprotein (AGP) concentration in non-symptomatic cats with feline coronavirus (FCoV) infection.
  19. ^ Plant lectins are potent inhibitors of coronaviruses by interfering with two targets in the viral replication cycle.
  20. ^ Infection of the tracheal epithelium by infectious bronchitis virus is sialic acid dependent.
  21. ^ Recognition of lactoferrin and aminopeptidase M-modified lactoferrin by the liver: involvement of the remnant receptor.
  22. ^ Lactoferricin-related peptides with inhibitory effects on ACE-dependent vasoconstriction.
  23. ^ Lactoferrin prevents dendritic cell-mediated human immunodeficiency virus type 1 transmission by blocking the DC-SIGN--gp120 interaction.
  24. ^ Human milk glycans protect infants against enteric pathogens.
  25. ^ Use of oromucosally administered interferon-alpha in the prevention and treatment of animal diseases.
  26. ^ Oromucosal cytokine therapy: mechanism(s) of action.
  27. ^ Oromucosal interferon therapy: relationship between antiviral activity and viral load.
  28. ^ Distribution of bovine milk sialoglycoconjugates during lactation.
  29. ^ Involvement of bovine lactoferrin metal saturation, sialic acid and protein fragments in the inhibition of rotavirus infection.
  30. ^ Changes in the mannan binding lectin (MBL) concentration in human milk during lactation.
  31. ^ Localization and biosynthesis of aminopeptidase N in pig fetal small intestine.
  32. ^ Folding of intestinal brush border enzymes. Evidence that high-mannose glycosylation is an essential early event.
  33. ^ Morphological and functional changes in the enterocyte induced by fructose.
  34. ^ Post-translational suppression of expression of intestinal brush border enzymes by fructose.
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