BEGIN:VCALENDAR VERSION:2.0 PRODID:-//Talks.cam//talks.cam.ac.uk// X-WR-CALNAME:Talks.cam BEGIN:VEVENT SUMMARY:Recent advances in the pathogenesis and diagnosis of feline corona virus infections. - Professor Saverio Paltrinieri\, Department of Animal Pathology\, Hygiene and Public Health\, University of Milan DTSTART:20120307T163000Z DTEND:20120307T173000Z UID:TALK35785@talks.cam.ac.uk CONTACT:Suzy Blows DESCRIPTION:Feline infectious peritonitis (FIP) is caused by the feline co ronavirus (FCoV). FCoV are widespread in feline populations and usually in fect enterocytes. During viral replication\, viral variants called “quas ispecies” are generated. Some of these “mutant” variants are able to replicate within macrophages and they spread throughout the body within t hese cells. Conversely “non-mutated” FCoVs can infect circulating mono cytes but are thought to be unable to replicate within these cells. The p recise mutation responsible for this different cell tropism has not yet be en identified. Nevertheless\, some polymorphic sequences of the viral geno me which are able to influence the host responses have been identified. Th is aspect is extremely important in the basis of the pathogenesis of FIP s ince ultimately the development of disease depends on the type of immune r esponse of the host: a strong cell-mediated immunity could protect FCoV-in fected cats from FIP\, whilst a weak cell-mediated immunity predisposes to FIP especially in the presence of hyperactivation of humoral immunity tha t induces an overproduction of anti-FCoV antibodies. In turn this induces the formation and deposition of immune complexes that determine a type II hypersensitivity reaction responsible for the vasculitis that characterize s the disease. \nInnate immunity is also thought to be involved in the pat hogenesis of FIP. The acute phase protein alpha1-acid glycoprotein (AGP) d ramatically increases and is hyposialylated in cats with FIP\, while hypes ialylated AGP transiently increases in clinically healthy cats when the nu mber of shedders in the cattery increases. This raised the hypothesis that AGP and AGP sialylation could play a role in protecting from or predispo sing FCoV infected cats to FIP. Recently this hypothesis has been supporte d by the finding that hyposialylated AGP depresses the phagocytic activity of feline phagocytes. \nDiagnosis\nBased on the pathogenesis described ab ove\, it is obvious that the simple detection of FCoV genome or of anti-FC oV antibodies is not useful for the diagnosis of FIP. FCov positive cats c ould actually be infected by “non mutated” viral variants and converse ly\, cats with FIP could have low antibody titers or low copies of viral g enome when deposition of immune complexes occurs. Conversely\, the detecti on of changes consistent with FCoV-induce tissue damage or with anti-FCoV responses could be diagnostic when FIP is clinically suspected. Specifical ly\, the following tests can be used (ranked in terms of diagnostic releva nce):\n- Histology: is considered the gold standard test and currently is the only method that confirms FIP\, especially if followed by immunohistoc hemistry (IHC) to detect FCoVs in the lesions. IHC on tru cut or FNA biop sies\, however\, has a low sensitivity.\n- Analysis of the effusions\, whe n present. The effusion is yellowish\, sticky\, contains fibrin clots and has a high specific gravity and a high protein content. This latter findin g is responsible for the positive Rivalta test\, for the electrophoretic p rofile found in effusion (increased alpha2 and gamma-globulin) and for the granular background detectable on cytological examination of the effusion s (other cytological findings are: non degenerated neutrophils\, macrophag es/mesothelial cells\, lymphocytes). If needed\, immunocytochemistry or im munofluorescence can be used to detect FCoVs within the macrophages detect ed cytologically. Conversely\, PCR on the effusions can provide both false positive and false negative results\, due to the kinetics of FCoV infecti on described above.\n- Serum protein electrophoresis: is one of the main d iagnostic findings for FIP. It is characterized by increased alpha 2 globu lins and by a polyclonal gammopathy \n- Serum AGP concentration. AGP incre ases in several inflammatory conditions\, including FIP. However\, increas ed of serum AGP are usually marked (higher than 1.5 mg/mL).\n- Other clini co-pathological findings reflect the inflammatory status associated with t he infection (e.g. normocytic normochromic non regenerative anemia\, lymph openia and neutrophilia) or the presence of tissue damage\, which is varia ble according to the organ(s) affected (e.g. increased creatinine/urea and /or increased hepatic enzymes\, etc…) \nNone of the above tests however \, is sufficient on it’s own\, to confirm the diagnosis of FIP. The diag nosis should be based on the pretest probability of disease\, which in tur n depends on a combination of history\, clinical findings and laboratory a bnormalities.\nTo date it is not possible to predict the probability of di sease in clinically healthy FCoV infected animals. Future studies should e stablish the possibility of using as biomarkers of resistance/susceptibili ty the quantitative and qualitative changes of molecules previously descri bed to be potentially involved in FCoV-host interactions.\nBibliografia\n1 . Addie D. D.\, Paltrinieri S.\, Pedersen N. C.: Reccommendations from wor kshops of the second international feline coronavirus/feline infectious pe ritonitis symposium. J. Feline Med. Surg. 6\; 125-130\, 2004.\n2. Addie D\ , Belák S\, Boucraut-Baralon C\, Egberink H\, Frymus T\, Gruffydd-Jones T \, Hartmann K\, Hosie MJ\, Lloret A\, Lutz H\, Marsilio F\, Pennisi MG\, R adford AD\, Thiry E\, Truyen U\, Horzinek MC.:Feline infectious peritoniti s. ABCD guidelines on prevention and management. J Feline Med. Surg. 11\; 594-604\, 2009.\n3. Paltrinieri S.\, Giordano A.\, Tranquillo V.\, Guazzet ti S.: Critical assessment of the diagnostic value of feline α1- acid gly coprotein for feline infectious peritonitis using likelihood ratios approa ch. J. Vet. Diagn. Invest. 29\; 266-272\, 2007.\n4. Pedersen N.C.: A revie w of feline infectious peritonitis virus infection: 1963 - 2008. J. Feline Med. Surg. 11\, 225-258\, 2009.\n5. Rossi G.\, Cornaro C.\, Battilani M.\ , Pocacqua V.\, Paltrinieri S.: Production of IFN-γ in feline whole blood after incubation with potential T-cell epitopes of the nucleocapsid prote in of feline coronavirus. Vet. Microbiol. 150\; 248–256\, 2011.\n6. Ritz S.\, Egberink H.\, Hartmann K.: Effect of feline interferon-omega on the survival time and quality of life of cats with feline infectious peritonit is. J. Vet. Intern. Med. 21\; 1193-1197\, 2007.\n7. Ishida T\, Shibanai A. \, Tanaka S.\, Uchida K.\, Mochizuki M.:“Use of recombinant feline inter feron and glucocorticoid in the treatment of feline infectious peritonitis . J Feline Med. Surg. 6\; 107-109\, 2004.\n8. Legendre A.M.\, Bartges J.W. : Effect of Polyprenyl Immunostimulant on the survival times of three cats with the dry form of feline infectious peritonitis. J. Feline Med. Surg. 11\; 624-626\, 2009.\n LOCATION:Lecture Theatre 1\, Department of Veterinary Medicine END:VEVENT END:VCALENDAR