Foot-and-mouth disease virus 12110 Foot-and-mouth disease Foot-and-mouth disease or hoof-and-mouth disease (Aphtae epizooticae) is an infectious and sometimes fatal viral disease that affects cloven-hoofed animals, including domestic and wild bovids. The virus causes a high fever for two or three days, followed by blisters inside the mouth and on the feet that may rupture and cause lameness. Foot-and-mouth disease is a severe plague for animal farming, since it is highly infectious and can be spread by infected animals through aerosols, through contact with contaminated farming equipment, vehicles, clothing or feed, and by domestic and wild predators. Its containment demands considerable efforts in vaccination, strict monitoring, trade restrictions and quarantines, and occasionally the elimination of millions of animals. Susceptible animals include cattle, water buffalo, sheep, goats, pigs, antelope, deer, and bison. It has also been known to infect hedgehogs and elephants, and llama and alpaca may develop mild symptoms, but are resistant to the disease and do not pass it on to others of the same species. In laboratory experiments, mice and rats and chickens have been successfully infected by artificial means, but it is not believed that they would contract the disease under natural conditions.Humans are very rarely affected. The virus responsible for the disease is a picornavirus, the prototypic member of the genus Aphthovirus. Infection occurs when the virus particle is taken into a cell of the host. The cell is then forced to manufacture thousands of copies of the virus, and eventually bursts, releasing the new particles in the blood. The virus is highly variable,which limits the effectiveness of vaccination (Wiki: Foot and mouth disease). 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 FMDV DNA Vaccine encoding P1 and non-structural proteins 2A, 3C, and 3D VO_0004553 DNA vaccine Research pcDNA3.1/P1-2A3C3D [Ref2674:Fowler et al., 2012] Intramuscular injection (i.m.) Intramuscular injection (i.m.) DNA vaccine construction DNA vaccine construction DNA vaccine construction DNA vaccine construction All DNA vaccinated cattle generated a detectable neutralising antibody response at 21 days post 1st vaccination (Fowler et al., 2012). Thirty-two cattle of 6–7 months of age were housed separately in six groups of five (vaccinated animals) and one group of two (un-vaccinated controls) within the isolation units at the Institute for Animal Health, Pirbright. The six groups of vaccinates were immunised as follows: Group 1 with 2 mg PLG-pcDNA3.1/P12A3C3D + 0.4 mg pcDNA3.1/bGM-CSF (DNA + PLG + GMCSF), Group 2 with 2 mg PLG-pcDNA3.1/P12A3C3D + 0.4 mg pcDNA3.1/bGM-CSF + electroporation (DNA + PLG + GMCSF + elec), Group 3 with 2 mg pcDNA3.1/P12A3C3D + 0.4 mg pcDNA3.1/bGM-CSF (DNA + GMCSF), Group 4 with 2 mg pcDNA3.1/P12A3C3D + 0.4 mg pcDNA3.1/bGM-CSF + electroporation (DNA + GMCSF + elec), Group 5 with 2 mg pcDNA3.1/P12A3C3D + electroporation (DNA + elec), and Group 6 with conventional vaccine (Fowler et al., 2012). VO_0003057 Conventionally vaccinated cattle were fully protected from experimental challenge, as determined by absence of generalised disease (Table 2). In addition 6 of the 8 DNA vaccinated cattle in groups 4 and 5 (DNA + GMCSF + elec and DNA + elec) were fully protected despite these DNA vaccinated animals being challenged 91 days after the protein boost (Fowler et al., 2012). On day 133 post primary vaccination, four cattle in each of vaccination groups 3–6 only were randomly selected, together with two un-vaccinated controls and intradermolingually challenged in two sites with 105 TCID50, 0.1 ml per site, of cattle adapted O1 Lausanne FMDV (Fowler et al., 2012). Foot and mouth disease DNA vaccine pWRMHX encoding a minimal self-cleaving ribozyme VO_0004320 DNA vaccine Research pWRM [Ref2153:Ward et al., 1997] Intramuscular injection (i.m.) Intramuscular injection (i.m.) DNA vaccine construction This vaccine encoded the genome of FMDV strain A12 and a minimal self-cleaving ribozyme from hepatitis delta virus (Ward et al., 1997), VO_0000286 Swine inoculated with pWRMHX did not show any signs of disease and produced neutralizing antibodies to FMDV, and 20% of the vaccinated animals were protected from FMDV challenge (Ward et al., 1997). Foot-and-Mouth Disease Virus Cationic Microparticle-coated DNA Vaccine VO_0004552 DNA vaccine Research pVAC-1D [Ref2673:Reddy et al., 2012] Intramuscular injection (i.m.) Intramuscular injection (i.m.) DNA vaccine construction Immunization with pVAC 1D-PLG elicited significantly enhanced neutralization antibody responses compared to naked DNA vaccine (Reddy et al., 2012). Sixty male guinea pigs of 10 weeks of age were divided in to three groups each containing 20 animals. Group I was inoculated with a 10 µg of pVAC- 1D (naked DNA vaccinated group), group II was inoculated with pVAC-1D coated on PLG microparticles (pVAC-1D + PLG group) and group III received PBS. All the animals were inoculated intramuscularly in the gluteal region of the right leg (Reddy et al., 2012). VO_0003057 Microparticles coated plasmid DNA-injected guinea pigs were protected when challenged with FMD virus (Reddy et al., 2012). Foot-and-Mouth Disease Virus DNA Vaccine pSinCMV-Vac-MEG990 VO_0004551 DNA vaccine Research Intramuscular injection (i.m.) Intramuscular injection (i.m.) the FMDV-specific MEG990 gene - 3 VP1 genes (Dar et al., 2012) DNA vaccine construction DNA vaccine construction DNA vaccine construction Immune responses included significant neutralizing antibody induction at all doses against all serotypes tested as compared to non-immunized controls, and delayed appearance and reduced severity of FMD lesions (Dar et al., 2012). Immunization of guinea pigs with the construct at dose rate of 10, 5, 2 and 1 μg per animal was through an intramuscular route (Dar et al., 2012). VO_0003057 Two of six and one of six guinea pigs were completely protected in 10 and 5 μg immunized groups (Dar et al., 2012). Viral challenge of guinea pigs was 4 week post-immunization with 1000 GPID(50) of FMDV serotype A (Dar et al., 2012). Foot-and-mouth disease virus vaccine rFMDVΔ3A^87-144 Recombinant vector vaccine Research Intradermal injection (i.d.) rFMDVΔ3A^87-144 vaccine induces potent immune response with 100% protective efficacy upon challenge with homologous virus in guinea pigs. (Dhanesh et al., 2020) MontanideISA-201 VG (Seppic, France) (Dhanesh et al., 2020) The rFMDVΔ3A^87-144 viruses were grown in BHK-21 monolayer in roller bottles and harvested after observing complete CPE. The virus supernatant was inactivated with 3 mM BEI for 24 h at room temperature after chloroform clarification. Three back passaging of the inactivated virus in BHK-21 were carried out to ensure the absence of residual infectivity. The inactivated virus was concentrated with PEG as described earlier and purified by cesium chloride density gradient ultracentrifugation to estimate the antigen content in the concentrated suspension by spectrophotometer. The vaccines were formulated by blending the PEG concentrated antigen and MontanideISA-201 VG adjuvant (Seppic, France) by homogenization to have 1.2 μg antigen per dose in 250 μl vaccine. (Dhanesh et al., 2020) Intradermal injection (i.d.) cDNA clone for FMDV serotype A Indian vaccine strain lacking 58 amino acid residues (87-144 amino acid position) in the carboxy-terminal region of the viral 3A protein. (Dhanesh et al., 2020) The FMDV^WT and rFMDVΔ3A^87-144 vaccinated group developed a mean serum titer of 1.38 log10SN50 and 1.35 log10SN50, respectively, on 28 dpv. Further, the serum titer of both the groups increased to 1.87 log10SN50 and 1.70 log10SN50, respectively, by 28 dpb, indicating a potent anamnestic immune response on second exposure with the antigen. Both conventional and the deletion mutant virus vaccine produced a similar immune response with no significant difference (p > 0.05). (Dhanesh et al., 2020) Thirty-six healthy male guinea pigs of 3 months age were randomly divided into three groups of 12 each. The first group received 1.2 μg of FMDV^WT virus antigen, and the second group received a similar dose of rFMDVΔ3A^87-144 virus antigen. The third group received phosphate-buffered saline to serve as the control. All the three groups received a similar dose of booster injections of respective antigen post 28 days of primary immunization. (Dhanesh et al., 2020) 100% protection was conferred by both vaccines as no systemic infection was noticed in any of the vaccinated animals. (Dhanesh et al., 2020) After 28 days post-booster, all the groups were challenged with 100 GPID50 of guinea pig adapted FMDV^WT in 50-μl volume by intradermal tracking in the left rear footpad. (Dhanesh et al., 2020) 1D Foot-and-mouth disease virus - type Asia 1 148800633 CDD:301302 CDD:119412 110195 ? 1D protein 9.49 22686.12 293 Picornavirus capsid protein domain_like. Picornaviruses are non-enveloped plus-strand ssRNA animal viruses with icosahedral capsids composed of 60 copies each of 4 virus encoded proteins; alignment includes picornaviridae, like poliovirus, hepatitis A...; cl13999 >ABR13034.1 1D protein, partial [Foot-and-mouth disease virus - type Asia 1] TTTTGESADPVTTTVENYGGETQTARRLHTDVAFVLDRFVKLTAPKNIQTLDLMQIPSHTLVGALLRSAT YYFSDLEVAIVHTGPITWVPNGSPKDALDNQTNPTAYQKQPVTRLALPYTAPHRVLATVYNGKTTYGETT ARRGDMAALAQRLSGRLPTSFNYGAVKAETITELLFRMKRAETYCPRPLLALDTTQDRRKQEIIAPEKQM M Protective antigen 1D Foot-and-mouth disease virus - type O 56675803 GOA:Q9DJ81 InterPro:IPR004080 UniProtKB/TrEMBL:Q9DJ81 12118 ? VP1 10.73 6939.818 126 >CAC22182.2 VP1, partial [Foot-and-mouth disease virus - type O] KAERALPTSFNYGAIKATRVTELLYRXKRAEXXXPRPXXAXHPSEARHKQKIVAPVXQX Protective antigen 1D Foot-and-mouth disease virus - type A 13399192 CDD:301302 CDD:119412 GOA:Q98VZ6 InterPro:IPR001676 InterPro:IPR004080 UniProtKB/TrEMBL:Q98VZ6 12111 ? VP1 9.7 22399.68 283 Picornavirus capsid protein domain_like. Picornaviruses are non-enveloped plus-strand ssRNA animal viruses with icosahedral capsids composed of 60 copies each of 4 virus encoded proteins; alignment includes picornaviridae, like poliovirus, hepatitis A...; cl13999 >CAC34727.1 VP1, partial [Foot-and-mouth disease virus - type A] TTATGESADPVTTTVENYGGETQVQRRHHTDIGFIMDRFVRIKNVSQTHVIDLMQTHQHGLVGALLRAAT YYFSDLEIVVKHDGNLTWVPNGAPESALSNTSNPTVYNKAPFTRLALPYTAPHRVLATVYNGTSKYAVGG SARRGDMGSLAARVARQLPSSFNYGAIKAENIHELLVRMKRAELYCPRPLLAIEVSSQDRHKQKIIAPAK QLL Protective antigen 2A Foot-and-mouth disease virus - type O 25121634 12118 ? 2A 3.88 2245.32 76 isolated from vesicular fluid of animals inoculated with field derived material in April 1997 >NP_740461.1 2A [Foot-and-mouth disease virus - type O] LLNFDLLKLAGDVESNPG Protective antigen 3C Foot-and-mouth disease virus - type O 25121639 CDD:201298 12118 ? 3C 8.06 21623.2 274 isolated from vesicular fluid of animals inoculated with field derived material in April 1997 >NP_740466.1 3C [Foot-and-mouth disease virus - type O] SGAPPTDLQKMVMGNTKPVELILDGKTVAICCATGVFGTAYLVPRHLFAEKYDKIMLDGRALTDSDYRVF EFEIKVKGQDMLSDAALMVLHRGNRVRDITKHFRDVARMKKGTPVVGVINNADVGRLIFSGEALTYKDIV VCMDGDTMPGLFAYRASTKAGYCGGAVLAKDGAETFIVGTHSAGGNGIGYCSCVSRSMLLKMKAHIDPEP HHE Protective antigen 3D Foot-and-mouth disease virus - type O 25121640 CDD:73158 12118 ? 3D 6.09 49457.15 534 isolated from vesicular fluid of animals inoculated with field derived material in April 1997 >NP_740467.1 3D [Foot-and-mouth disease virus - type O] GLIVDTRDVEERVHVMRKTKLAPTVAHGVFNPEFGPAALSNKDPRLNEGVVLDDVIFSKHKGDTRMSEED KALFRRCAADYASRLHSVLGTANAPLSVYEAIKGVDGLDAMEPDTAPGLPWALQGKRRGALIDFENGTVG PEVEAALKLMESREYKFVCQTFLKDEIRPLEKVRAGKTRIVDVLPVEHILYTRMMIGRFCAQMHSNNGPQ IGSAVGCNPDVDWQRFGTHFAQYKNVWDVDYSAFDANHCSDAMNIMFEEVFRTEFGFHPNAEWILKTLVN TEHAYENKRIVVEGGMPSGCSATSIINTILNNIYVLYALRRHYEGVELDTYTMISYGDDIVVASDYDLDF EALKPHFKSLGQTITPADKSDKGFVLGHSITDVTFLKRHFHMDYGTGFYKPVMASKTLEAILSFARRGTI QEKLISVAGLAVHSGPDEYRRLFEPFQGLFEIPSYRSLYLRWVNAVCGDA Protective antigen FMDV A12 genome Foot-and-mouth disease virus - type A strain A12-119 46810760 46810761 CDD:283147 CDD:286076 CDD:278501 CDD:119412 CDD:301302 CDD:279280 CDD:278947 CDD:279070 CDD:238843 12111 ? polyprotein 6.78 242060.45 2432 Plum Island Animal Disease Center Virus Collection, isolated 1932, vaccine >AAT01695.1 polyprotein [Foot-and-mouth disease virus - type A] MNTTNCFIALVHAIREIRAFFLSRATGKMEFTLYNGERKTFYSRPNNHDNCWLNTILQLFRYVDEPFFDW VYNSPENLTLAAIKQLEELTGLELHEGGPPALVIWNIKHLLQTGIGTASRPSEVCMVDGTDMCLADFHAG IFLKGQEHAVFACVTSNGWYAIDDEDFYPWTPDPSDVLVFVPYDQEPLNGGWKANVQRKLKGAGQSSPAT GSQNQSGNTGSIINNYYMQQYQNSMDTQLGDNAISGGSNEGSTDTTSTHTTNTQNNDWFSKLASSAFTGL FGALLADKKTEETTLLEDRILTTRNGHTTSTTQSSVGVTYGYSTEEDHVAGPNTSGLETRVVQAERFFKK FLFDWTTDKPFGHLEKLELPTDHHGVFGHLVDSYAYMRNGWDVEVSAVGNQFNGGCLLVAMVPEWKEFDK REKYQLTLFPHQFISPRTNMTAHITVPYLGVNRYDQYKKHKPWTLVIMVVSPLTVSNTAATQIKVYANIA PTYVHVAGELPSKEGIFPVACSDGYGGLVTTDPKTADPVYGKVYNPPRTNYPGRFTNLLDVAEACPTFLC FDDGKPYVVTRTDDTRLLAKFDVSLAAKHMSNTYLSGIAQYYTQYSGTINLHFMFTGSTDSKARYMVAYI PPGVETPPETPEGAAHCIHAEWDTGLNSKFTFSIPYVSAADYAYTASDTAETTNVQGWVCIYQITHGKAE GDTLVVSASAGKDFELRLPIDPRSQTTATGESADPVTTTVENYGGETQVQRRHHTDVSFIMDRFVKIKSL NPTHVIDLMQTHQHGLVGALLRAATYYFSDLEIVVRHDGNLTWVPNGAPEAALSNTGNPTAYNKAPFTRL ALPYTAPHRVLATVYNGTNKYSASGSGVRGDSGSLAPRVARQLPASFNYGAIKAETIHELLVRMKRAELY CPRPLLAIEVSSQDRHKQKIIAPGKQLLNFDLLKLAGDVESNPGPFFFADVRSNFSKLVDTINQMQEDMS TKHGPDFNRLVSAFEELATGVKAIRTGLDEAKPWYKLIKLLSRLSCMAAVAARSKDPVLVAIMLADTGLE ILDSTFVVKKISDSLSSLFHVPAPVFSFGAPVLLAGLVKVASSFFRSTPEDLERAEKQLKARDINDIFAI LKNGEWLVKLILAIRDWIKAWIASEEKFVTTTDLVPGILEKQRDLNDPSKYKEAKEWLDNARQACLKSGN VHIANLCKVVAPAPSKSRPEPVVVCLRGKSGQGKSFLANVLAQAISTHFTGRTDSVWYCPPDPDHFDGYN QQTVVVMDDLGQNPDGKDFKYFAQMVSTTGFIPPMASLEDKGKPFNSKVIIATTNLYSGFTPRTMVCPDA LNRRFHFDIDVSAKDGYKINNKLDIIKALEDTHTNPVAMFQYDCALLNGMAVEMKRMQQDMFKPQPPLQN VYQLVQEVIERVELHEKVSSHPIFKQISIPSQKSVLYFLIEKGQHEAAIEFFEGMVHDSIKEELRPLIQQ TSFVKRAFKRLKENFEIVALCLTLLANIVIMIRETRKRQKMVDDAVNEYIEKANITTDDTTLDEAEKNPL ETSGASTVGFRERTLTGQRACNDVNSEPARPAEEQPQAEGPYTGPLERQRPLKVRAKLPQQEGPYAGPLE RQKPLKVKAKAPVVKEGPYEGPVKKPVALKVKAKNLIVTESGAPPTDLQKMVMGNTKPVELILDGKTVAI CCATGVFGTAYLVPRHLFAEKYDKIMLDGRAMTDSDYRVFEFEIKVKGQDMLSDAALMVLHRGNRVRDIT KHFRDTARMKKGTPVVGVVNNADVGRLIFSGEALTYKDIVVCMDGDTMPGLFAYKAATKAGYCGGAVLAK DGADTFIVGTHSAGGNGVGYCSCVSRSMLLRMKAHVDPEPHHEGLIVDTRDVEERVHVMRKTKLAPTVAH GVFNPEFGPAALSNKDPRLNEGVVLDEVIFSKHKGDTKMSAEDKALFRRCAADYASRLHSVLGTANAPLS IYEAIKGVDGLDAMESDTAPGLPWAFQGKRRGALIDFENGTVGPEVEAALKLMEKREYKFACQTFLKDEI RPMEKVRAGKTRIVDVLPVEHILYTRMMIGRFCAQMHSNNGPQIGSAVGCNPDVDWQRFGTHFAQYRNVW DVDYSAFDANHCSDAMNIMFEEVFRTDFGFHPNAEWILKTLVNTEHAYENKRITVEGGMPSGCSATSIIN TILNNIYVLYALRRHYEGVELDTYTMISYGDDIVVASDYDLDFEALKPHFKSLGQTITPADKSDKGFVLG HSITDVTFLKRHFHIDYGTGFYKPVMASKTLEAILSFARRGTIQEKLTSVAGLAVHSGPDEYRRLFEPFQ GLFEIPSYRSLYLRWVNAVCGDA Protective antigen P1 Foot-and-mouth disease virus - type O 15419537 CDD:286076 CDD:278501 CDD:119412 CDD:301302 12118 ? polyprotein P1 6.71 75741.482 824 isolated from a field outbreak in 1979 >AAK97050.1 polyprotein P1, partial [Foot-and-mouth disease virus - type O] GAGQSSPATGSQNQSGNTGSIINNYYMQQYQNSMDTQLGDNAISGGSNEGSTDTTSTHTTNTQNNDWFSK LASSAFSGLFGALLADKKTEETTLLEDRILTTRNGHTTSTTQSSVGVTYGYATAEDFVRGPNTSGLETRV IQAERFFKTHLFDWVTSDSFGRCHLLELPTDHKGVYGSLTDSYAYMRNGWDVEVTAVGNQFNGGCLLVAM VPELCSIQKRELYQLTLFPHQFINPRTNLTAHITVPFIGVNRYDQYXVHKPWTLVVMVVAPLTVNTEGAP QIKVYANIAPTNVHVAGEFPSKEGIFPVACSDGYGGLVTTDPKTADPAYGKVFNPPRNMLPGRFTNFLDV AEACPTFLRFEGGVPYVTSKTESDRVLTRFDLSLAAKHMSNTFLAGLAQYYTQYSGTINLHFMFTGPTDA KARYMIAYAPPGMEPPKTPEAAAHCIHAEWDTGLNSKLTFSIPYLSAADYAYTASDTAETTNVQGWVCLF QITHGKADGDALVVLASAGKDFEVRLPVDARTQTTSAGESADPVTATVENYGGETQVQRRQHTDVSFILD RFVKVTPEDQINVLDLMQTPAHTLVGALLRTATYYFADLEVAVKHEGNLTWVPNGAPETALDNTTNPTAY HKAPLTRLALPYTAPHRVLATVYNGNCRYGESTVTNVRGDLQVLAQKAARTLPTSFNYGAIKATRVIELL YRMKRAETYCPRPLLAIHPNEARHKQKIVAPVKQLL Protective antigen Joyappa et al., 2009 journal Joyappa DH, Kumar CA, Banumathi N, Reddy GR, Suryanarayana VV 2009 139 1-2 58-66 Veterinary microbiology Shao et al., 2005 journal Shao HJ, Chen L, Su YB 2005 29 1 35-46 Veterinary research communications Wang et al., 2006 journal Wang F, He XW, Jiang L, Ren D, He Y, Li DA, Sun SH 2006 24 12 2017-2026 Vaccine Ward et al., 1997 journal Ward G, Rieder E, Mason PW 1997 71 10 7442-7447 Journal of virology Wiki: Foot and mouth disease website http://en.wikipedia.org/wiki/Foot-and-mouth_disease