Feline infectious peritonitis virus 11135 The pathogenesis of FIP may be explained by an increased number of mutants, stochastically arising during bursts of replication (eg, under immune suppression), some of them growing to high concentrations in monocytes and macrophages. Mutations have been identified in non-structural genes, and more may remain to be identified. These highly virulent FPIV mutants have consistently induced FIP under experimental conditions, but their virulence has not been traced to a molecular source. The viral load and the cat’s immune response determine whether FIP will develop. Both viral genetics and host immunity are likely to play a role in the development of FIP. The pathology of FIP has been classified into two forms: an effusive (wet) FIP characterised by polyserositis (eg, thoracic and abdominal effusion)and vasculitis, and a non-effusive (dry) FIP characterised by granulomatous lesions in organs (Addie et al., 2009). Feline infectious peritonitis (FIP) It has been suggested that cats mounting a strong cell-mediated immune response do not develop FIP, whereas cats showing a predominantly humoral response progress to disease. Hypergammaglobulinaemia is common in cats with FIP. Also, a drastic depletion of T cells from blood and lymphoid tissues has been described (Addie et al., 2009). Domestic cats Feline infectious peritonitis virus (FIPV) is a feline coronavirus that causes feline infectious peritonitis. Infection is ubiquitous in domestic cats, especially where conditions are crowded. FIPV can survive in for 7 weeks in a dry environment and may be transmitted indirectly via fomites. FPIV is an enveloped single stranded RNA virus. Most FIPV-infected cats either stay healthy or show only a mild enteritis. Only a proportion of FPIV-infected cats will develop FIP, a pyogranulomatous vasculitis (Addie et al., 2009). Baboon Papio cynocephalus 9556 Bank vole Clethrionomys glareolus 447135 Bear Ursus americanus 9643 Birds Passeroidea 175121 Brown Trout Salmo trutta 8032 Buffalo Bison bison 9901 Carnivores Vulpes 9625 Cat Felis catus 9685 Catfishes Siluriformes 7995 Cattle Bos taurus 9913 Chicken Gallus gallus 9031 Chimpanzee Pan troglodytes 9598 chinchillas Chinchillidae 10150 Copper Pheasant Syrmaticus soemmerringii 9067 Deer Cervus elaphus 9860 Deer mouse Peromyscus maniculatus 10042 Dog Canis familiaris 9615 Ducks Anas 8835 Ferret Mustela putorius furo 9669 Fish Hyperotreti 117565 Gerbil Gerbillina 10045 Goat Capra hircus 9925 Gray wolf Canis lupus 9612 Guinea pig Cavia porcellus 10141 Hamster Mesocricetus auratus 10036 Horse Equus caballus 9796 Human Homo sapiens 9606 Macaque Macaca fascicularis 9541 Mongolian Gerbil Meriones unguiculatus 10047 Monkey Platyrrhini 9479 Mouse Mus musculus 10090 None None Parrot Psittacidae 9224 Pig Sus scrofa 9823 Rabbit Oryctolagus cuniculus 9986 Rainbow trout Oncorhynchus mykiss 8022 Rat Rattus 10114 Raven Corvus corax 56781 sei whale Balaenoptera borealis 9768 Sheep Ovis aries 9940 Squirrel Spermophilus richardsonii 37591 Tree shrew Tupaiidae 9393 Trouts, salmons & chars Salmoninae 504568 Turkey Meleagris gallopavo 9103 Vole Microtus ochrogaster 79684 Water buffalo Bubalus bubalis 391902 Feline infectiors peritonitis serum vaccine Serum contianing ant-FIPV. Research Intravenous injection (i.v.) A serum containing anti-FIBV produced by an asymptomatic cat was injected into other cats.(Weiss and Scott, 1981) A healthy 5-month-old kitten with an F1PV serum antibody titer greater than 1:1600 served as the immune serum donor. This animal was an SPF kitten who had seroconverted by natural exposure to FIPV-shedding contact cats and had remained asymptomatic.(Weiss and Scott, 1981) Intravenous injection (i.v.) FIPV (Weiss and Scott, 1981) Serum was administered by slow intravenous injection and given at a dosage of 11 ml/kg per cat.(Weiss and Scott, 1981) Not protected, higher fatality rate than unvaccinated cats. (Weiss and Scott, 1981) Six hr after administration of serum, the experimental kittens were inoculated intraperitoneally with 0.5 ml of FIPV- infected liver homogenate. Feline infectiour peritonitis virus 3abc mutant vaccine VO_0002961 Live, attenuated vaccine Research Oronasal immunization Oronasal immunization Gene mutation This 3abc mutant is from Feline infectious peritonitis virus (Haijema et al., 2004). Gene mutation This 3abc mutant is from Feline infectious peritonitis virus (Haijema et al., 2004). Gene mutation This 3abc mutant is from Feline infectious peritonitis virus (Haijema et al., 2004). A 3abc mutant is attenuated in kittens (Haijema et al., 2004). A 3abc mutant induces protection in kittens from challenge with wild type FIPV (Haijema et al., 2004). Feline Infectious Peritonitis Modified Live Virus Vaccine (USDA: 15A1.20) Pfizer, Inc. VO_0001544 Live, attenuated vaccine Licensed USA Feline infectious peritonitis virus 7ab mutant vaccine VO_0002964 Live, attenuated vaccine Research Oronasal immunization Oronasal immunization Gene mutation This 7ab mutant is from Feline infectious peritonitis virus (Haijema et al., 2004). Gene mutation This 7ab mutant is from Feline infectious peritonitis virus (Haijema et al., 2004). A 7ab mutant is attenuated in kittens (Haijema et al., 2004). A 7ab mutant induces protection in kittens from challenge with wild type FIPV (Haijema et al., 2004). Feline infectious peritonitis virus recombinant N proteins vaccine Recombinant vector vaccine Research subcutaneous injection Cell lysate with baculovirus-expressed N protein of the Type I FIPV strain KU-2 recombinant vaccine was effective in preventing the progression of FIP without inducing antibody-dependent enhancement of FIPV infection in cats. (Hohdatsu et al., 2003) 2% aluminum hydroxide gels and L80 SF-9 cells cultured for 2 days were inoculated with the recombinant baculovirus. After absorption for 1 h, serum-free TC-100 medium was added to the cells and the cells were cultured at 27 °C. After culture for 96 h, the infected cells were recovered and washed with PBS. One milliliter of RSB buffer containing 0.2% NP-40 (0.01 M NaCl, 0.0015 M MgCl2, 0.01 M Tris–HCl, pH 7.4) was added to 1×107 cells and the cell suspension was kept at 4 °C for 30 min with occasional shaking. The cells were centrifuged at 800×g for 10 min. The precipitate was resuspended in PBS and used as recombinant N protein. Feline inactivated trivalent vaccine (Felidovac PCR; Intervet, The Netherlands), which is commercially available in Japan, was added to the recombinant N protein as an adjuvant. This feline inactivated trivalent vaccine contains 2% aluminum hydroxide gels and L80 as an adjuvant. (Hohdatsu et al., 2003) subcutaneous injection baculovirus-expressed N protein of the Type I FIPV strain KU-2 (Hohdatsu et al., 2003) Recombinant protein preparation (Hohdatsu et al., 2003) In all vaccinated cats, the ELISA value against N protein began to increase on Day 6 after the challenge and the antibody responded earlier than that in the control cats. The anti-challenge virus (strain 79-1146) neutralizing antibody production converted to positive on Day 12 after the challenge in the vaccination and control groups, showing no significant difference between the two groups. (Hohdatsu et al., 2003) Eight SPF cats aged 6 months and eight SPF cats aged 7–9 months were used in the first and second experiments, respectively. In both experiments, four cats were subcutaneously vaccinated three times with 3-week intervals. The same vaccination/challenge experiment was repeated twice. (Hohdatsu et al., 2003) Combining the results of the first and second experiments, the survival rates were 75% (6/8) and 12.5% (1/8) for the immunized and control groups, respectively. These survival rates were analyzed using the X2-test, and there was a significant difference (P<0.05). (Hohdatsu et al., 2003) As a challenge control, four cats received a subcutaneous administration of the SF-9 cell-derive d antigen, which was prepared as the recombinant N protein described above, with the adjuvant. Four weeks after the third vaccination, all cats were challenged oronasally with 105 TCID50 FIPV strain 79-1146. (Hohdatsu et al., 2003) 3a Feline infectious peritonitis virus 10040181 315192965 FIPV_gp03 AY994055 YP_004070195 11135 24860 25075 ? putative 3a protein 4.49 6974.53 71 >gi|315192962:24860-25075 Feline infectious peritonitis virus, complete genome TATGGACATTGTCAAATCTATTGACATATTCGTAGACGCTGTACTTGACGAACTTGACCGTGCATACTTT GCTGTAACTCTTAAAGTAGAATTTAAGACTGGTAAACTACTTGTGTGTATAGGTTTTGGTGACACACTTC TTGAGGCTAAGGACAAAGCGTATGCTAAGCTTGGTCTCTCCTTTATTGAAGAAGTCAATAGTCATACAGT TGTTTA >gi|315192965|ref|YP_004070195.1| putative 3a protein [Feline infectious peritonitis virus] MDIVKSIDIFVDAVLDELDRAYFAVTLKVEFKTGKLLVCIGFGDTLLEAKDKAYAKLGLSFIEEVNSHTV V Virmugen A 3abc deletion mutant in Feline infectious peritonitis virus (FIPV) was attenuated and provided protection against virulent FIPV strain 79-1146 challenge in kittens [Ref1986:Haijema et al., 2004]. 3b Feline infectious peritonitis virus 10040182 315192966 FIPV_gp04 AY994055 YP_004070196 11135 25020 25235 ? putative 3b protein 11.43 7960.26 71 >gi|315192962:25020-25235 Feline infectious peritonitis virus, complete genome TATGCTAAGCTTGGTCTCTCCTTTATTGAAGAAGTCAATAGTCATACAGTTGTTTAGTATTACTGTTTAC AAGTTTAAAGCCAAATTTTGGTATAAACTACCTTTTGAAACTAGACTTTGTATCATTAAACACACAAGAC CCAAAGCATTAAGTGTTACAAAACAAGTAAAGAGAGATTATAGAAAAATTGCCATTCTAAATTCCATGCG AAAATG >gi|315192966|ref|YP_004070196.1| putative 3b protein [Feline infectious peritonitis virus] MLSLVSPLLKKSIVIQLFSITVYKFKAKFWYKLPFETRLCIIKHTRPKALSVTKQVKRDYRKIAILNSMR K Virmugen A 3abc deletion mutant in Feline infectious peritonitis virus (FIPV) was attenuated and provided protection against virulent FIPV strain 79-1146 challenge in kittens [Ref1986:Haijema et al., 2004]. 3c Feline infectious peritonitis virus 10040183 FIPV_gp05 11135 25232 25966 ? >gi|315192962:25232-25966 Feline infectious peritonitis virus, complete genome AATGATTGGTGGACTTTTTCTTAACACTCTTAGTTTTGTAATTGTTAGTAACCATGTTATTGTTAATAAC ACAGCAAATGTGCATACTACACAACATGAAAATGTTATAGTACAACAGCATTAGGTTGTTAGTGCTAGAA CACAAAATTATTACCCAGAGTTCAGCATCGCTGTACTCTTTGTATCATTTTTGGCTTTGTACCGTAGTAC AAACTTTAAGACGTGTGTCGGCATCTTAATGTTTAAGATTGTATCAATGACACTTGTAGGGCCTATGCTT ATAGCATATGGTTACTACATTGATGGCATTGTTACAATAACTGTCTTAGCTTTAAGATTTTTCTACTTAG CATACTTTTGGTATGTTAATAGTAGGTCCGAATTTATTTTATACAATACAACGACACTCATGTTTGTACA TGGCAGAGCTGCACCGTTTATGAGAAGTTCTCACAGCTCTATTTATGTCACATTGTATGGTGGCATAAAT TATATGTTTGTGAATGACCTCACGTTGCATTTTGTAGACCCTATGCTTGTAAGAATAGCAATACGTGGCT TAGCTCATGCTGATCTAACTGTTTTTAGAGCAGTTGAACTTCTCAATGGTGATTTTATATATGTATTTTC ACAGGAGCCCGTAGCCGGTGTTTACAATGCAGCCTCTTCTCAGGCGGTTCTAAACGAAATTGACTTAAAA GAAGAAGAAGAAGACCATAACTATGACGTTCCCTA Virmugen A 3abc deletion mutant in Feline infectious peritonitis virus (FIPV) was attenuated and provided protection against virulent FIPV strain 79-1146 challenge in kittens [Ref1986:Haijema et al., 2004]. 7a Feline infectious peritonitis virus 10040187 315192970 FIPV_gp09 AY994055 YP_004070200 11135 28151 28456 ? non-structural protein 7a 8.52 9843.18 101 >gi|315192962:28151-28456 Feline infectious peritonitis virus, complete genome CATGCTCGTTTTCGTCCATGCTGTACTTGTAACAGCTTTAATCTTACTACTAATTGGTAGAATCCAATTA CTAGAAAGGTTGTTACTCAGTCATCTGCTTAATCTTACAACAGTCAGTAATGTTTTAGGTGTGCCTGACA GTAGTCTGCGTGTAAATTGTTTGCAGCTTTTGAAACCAGACTGCCTTGATTTTAATATCTTACATAAAGT TTTAGCAGAAACCAGGTTACTAGTAGTAGTACTGCGAGTGATCTTTCTAGTTCTTCTAGGGTTTTCCTGC TATACATTGTTGGGTGCATTATTTTA >gi|315192970|ref|YP_004070200.1| non-structural protein 7a [Feline infectious peritonitis virus] MLVFVHAVLVTALILLLIGRIQLLERLLLSHLLNLTTVSNVLGVPDSSLRVNCLQLLKPDCLDFNILHKV LAETRLLVVVLRVIFLVLLGFSCYTLLGALF Virmugen A 7ab deletion mutant in Feline infectious peritonitis virus is attenuated and provides protection against virulent FIPV strain 79-1146 challenge in kittens [Ref1986:Haijema et al., 2004]. 7b Feline infectious peritonitis virus 10040188 315192971 FIPV_gp10 AY994055 YP_004070201 11135 28461 29081 ? non-structural protein 7b 7.25 22221.54 206 >gi|315192962:28461-29081 Feline infectious peritonitis virus, complete genome CATGATTGTTGTAATCCTTGTGTGTATCTTTTTGGCTAATGGAATTAAAGCTACTGCTGTGCAAAATGAC CTTCATGAACATCCCGTTCTTACCTGGGATTTATTACAGCATTTCATAGGACATACCCTCTACATTACAA CACACCAGGTCTTAGCACTACCGCTTGGATCTCGTGTTGAGTGTGAGGGTATCGAAGGTTTCAATTGCAC ATGGCCTGGCTTTCAAGATCCTGCACATGATCATATTGATTTCTACTTTGATCTTTCTAATCCTTTCTAT TCATTTGTAGATAATTTTTATATTGTAAGTGAGGGAAATCAAAGAATCAATCTCAGATTGGTTGGTGCTG TGCCAAAACAAAAGAGATTAAATGTTGGTTGTCATACATCATTTGCTGTTGATCTTCCATTTGGGATTCA GATATACCATGACAGGGATTTTCAACACCCTGTTGATGGCAGACATCTAGATTGTACTCACAGAGTGTAC TTTGTGAAGTACTGTCCACATAACCTGCATGGTTATTGCTTTAATGAGAGGCTGAAAGTTTATGACTTGA AGCAATTCAGAAGCAAGAAGGTCTTCGACAAAATCAACCAACATCATAAAACTGAGTTATA >gi|315192971|ref|YP_004070201.1| non-structural protein 7b [Feline infectious peritonitis virus] MIVVILVCIFLANGIKATAVQNDLHEHPVLTWDLLQHFIGHTLYITTHQVLALPLGSRVECEGIEGFNCT WPGFQDPAHDHIDFYFDLSNPFYSFVDNFYIVSEGNQRINLRLVGAVPKQKRLNVGCHTSFAVDLPFGIQ IYHDRDFQHPVDGRHLDCTHRVYFVKYCPHNLHGYCFNERLKVYDLKQFRSKKVFDKINQHHKTEL Virmugen A 7ab deletion mutant in Feline infectious peritonitis virus is attenuated and provides protection against virulent FIPV strain 79-1146 challenge in kittens [Ref1986:Haijema et al., 2004]. N Feline infectious peritonitis virus BAC01159 CDD:279305 11135 nucleocapsid 10.35 40532.64 447 Coronavirus nucleocapsid protein; pfam00937 >BAC01159.1 nucleocapsid [Feline infectious peritonitis virus] MATQGQRVNWGDEPSKRRDRSNSRGRKNGNIPLSYFNPITLESGSKFWNICPRDFVPKGIGNKDQQIGYW NRQVRYRIVRGQRKELPERWFFYFSGTGPHADAKFKDKIDGVFWVARDGAMNKPTTLGTRGTNNESKPLK FDGKIPPQFQLEVNRSRNNSRSGSQPRSVSRSRSQSRGRQQSNNQNTNVEDTIVAVLSKLGVTDKQRSRS KSGERNQSKPRDTTPKNANKHTWKKTAGKGDVTNFYGARSSSANFGDSDLVANGNAAKCYPQIAECVPSA SSILFGSQWSAEEAGDQVKVTLTHTYYLPKDDAKTSQFLEQIDAYKQPSEVAKDQRQRKSRSKSADKKPE ELSVTLVEAYTDVFDDTQVEMIDEVTN Protective antigen [Ref4956:Takano et al., 2014] Addie et al., 2009 journal 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, Radford AD, Thiry E, Truyen U, Horzinek MC 2009 11 7 594-604 Journal of feline medicine and surgery Haijema et al., 2004 journal Haijema BJ, Volders H, Rottier PJ 2004 78 8 3863-3871 Journal of virology Satoh et al., 2011 journal Satoh R, Furukawa T, Kotake M, Takano T, Motokawa K, Gemma T, Watanabe R, Arai S, Hohdatsu T 2011 29 9 1791-1800 Vaccine Takano et al., 2014 journal Takano T, Tomizawa K, Morioka H, Doki T, Hohdatsu T 2014 19 7 645-650 Antiviral therapy