Reticuloendotheliosis Virus 11636 Tumors, wasting syndrome REV is a group of avian viruses in the family Retroviridae, specifically gammaretroviruses in the same genus as mammalian C-type retroviruses. The viruses included in this group are REV strains such as REV-T (replication defective and tumorigenic); REV-A (REV-T helper, replication competent); spleen necrosis virus; chick syncytial virus; duck infectious anemia virus; and other isolates obtained from turkeys, chickens, ducks, pheasants, geese, and prairie chickens. Notably, REV infection of captive prairie chicken can result in a high incidence (up to 100% of infected birds in some outbreaks) of tumors and wasting syndrome, and this infection has had a severe impact on the APC recovery program (Collisson, pers. obs.). Once detected, infected birds were removed from breeding populations, significantly reducing the genetic pool and the number of birds that can be released or kept as breeders. REV infection has been associated with acute reticular cell neoplasia, wasting disease, and chronic cell neoplasia of lymphoid and nonlymphoid tissues (Drechsler et al., 2013). 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 REV DNA vaccine VP22/gag and VP22/env VO_0004588 DNA vaccine Research pcDNA3.1 [Ref2727:Drechsler et al., 2013] Intramuscular injection (i.m.) Intramuscular injection (i.m.) DNA vaccine construction DNA vaccine construction DNA vaccine construction Four birds (two males, two females) were vaccinated four times with a combination of 500 μg of VP22/gag and 250 μg of VP22/env plasmids expressing the fusion proteins (Drechsler et al., 2013). VO_0003057 The DNA vaccine containing REV proteins env and gag protected against infection early after birds were repeatedly inoculated with large doses of vaccine (500 μg) as evidenced by the lack of proviral DNA in lymphocytes of the vaccinated birds at 4 wk postchallenge. In contrast, nested PCR 4 wk postinfection showed REV proviral DNA in several of the PBS and vector mock-vaccinated control birds. However, 8 wk postinfection, two out of three vaccinated birds tested positive for REV, and all birds were positive 12 wk postinfection, showing that the vaccine delayed, thus inhibited, the onset of viral replication (Drechsler et al., 2013). REV gp90 Vaccine Recombinant vector vaccine Research Intramuscular injection (i.m.) gp90 protein-based vaccine derived from a Reticuloendotheliosis virus strain isolated from a contaminated IBD vaccine induces protection in chicks. (Ren et al., 2018) CpG-ODN Intramuscular injection (i.m.) gp90 (Ren et al., 2018) Recombinant protein preparation encodes the surface glycoprotein (gp90) (Ren et al., 2018) Starting from the second week post-immunization, the REV antibody titer of the immunized hens increased rapidly, especially from weeks 6 to 8 post-immunization. The positive rate of antibody reached 100% and the antibody titer peaked at week 9 post-immunization. Three eggs were collected from each hen to determine if the egg yolks contained REV-specific antibody were consistent with the serum antibody test results. Hens in the control group were always antibody negative. (Ren et al., 2018) Twenty 150-day-old SPF chickens were obtained from SPAFAS and randomly divided into two groups. Each chicken of immune group was immunized with 600 μg gp90 protein and 300 μg CPG-ODN. The control group was immunized with an equal volume of PBS and immunized once every two weeks (150, 164, 178, 182 days age). Eggs were collected from the immunized hens and REV-specific antibody was measured in the egg yolk. (Ren et al., 2018) At the sixth week after challenge, compared to five chicks in the control group, only one chick in the immunized group was viremic. One of the chicks in the control group died without any specific symptom during the sixth week. The presence of maternal antibodies in the chicks significantly affected the health and survival of chicks after REV infection, as supported by chicks in the control group always having a lower bodyweight than chicks in the immunized group. (Ren et al., 2018) Ten hatched 1-day-old chicks from the two experimental cohorts, which were REV maternal antibody positive or negative, were challenged intraperitoneally with 102.7 TCID50 of the REV-LN1201 strain. (Ren et al., 2018) env Reticuloendotheliosis virus strain APC-566 88605105 CDD:278837 CDD:197368 11636 ? env protein 6.13 60964.83 650 ENV polyprotein (coat polyprotein); pfam00429 >ABD46830.1 env protein [Reticuloendotheliosis virus] MDCLTNLRSAEGKVDQAGKTLILLVVWWGFGTTAEGYPLQQLWGLPCDCSGGYVFSIPTYYTNSLDCGSS TAYLTYGSGTGSWGWGGGFRQQWECVFKPKIIPSVQGQPGPCPSECLTIATQMHSTCYEKAQECTLLGKT YFTAILQKTKLGSYEDGPNKLLQASCTGTIGKPVCWDPVAPVYVSDGGGPTDMIREESVRERLEEIIRHS YPSVQYHPLALPRPRGVDLDPQTYDILEATHQVLNATNPQLAENCWLCMTLGTPIPAAIPANGNVTLDGN CSLSLPFRVQPTGSIDVNCYAGEADNRTGIPIGYVHFTNCTSIQEVSNETSHIRNLTRLCPPPGHVFVCG NNMAYTALPNKWIGLCILASIVPDMSIISGEEPIPLPSIEYTAGRHKRAVQFIPLLVGLGITGATLAGGT GLGVSVHTYHKLSNQLIEDVQALSGTINDLQDQIDSLAEVVLQNRRGLDLLTAEQGGICLALQEKCCFYA NKSGIVRDKIRKLQEDLIARKRALYDNPLWNGLNGFLPYLLPLLGPLFGLILFLTLGPCIIKTLTRIIHD KIQAVKILALVPQYKPLPTEMDTLGQ Protective antigen gag Reticuloendotheliosis virus strain APC-566 88605103 CDD:307339 CDD:307969 CDD:197667 11636 ? gag protein 8.36 53536.51 562 Matrix protein (MA), p15; pfam01140 >ABD46828.1 gag protein [Reticuloendotheliosis virus] MGQAGSKGLLTPLECILKNFSDFKKRAGDYGEDVDSFTLRKLCELEWPTFGVGWPKEGTLDFRVVAAVRN IVFGNPGHPDQVIYITVWIDITIERPKYLKDCGCKPTGPSKVLLASQKVNPRRPVLPSAPESPPRMRRAQ FLDERPLSPAPAPPPPYPEVPAIAEEGEEGQQPDSTVMASPPHTRSGLEFGAQGPSGMYPLRETGERDMG GRPMRTYVPFTTSDLYNWKNQNPSFSQAPDEVISLLESVFYTHQPTWDDCQQLLRTLFTTEERERVRTES RREVRNDQGVQVTDEREIEAQFPATRPDWDPNTGRGNDNLERYRQILLRGLRAAARKPTNLSKITEVRQG ADESPTAYLERLYQAYRTWSPIDPRAPENQAAIVIQFVSQSAPDIRKKIQKIDGFQGKSLSELVAIAQKV FDQREDPAKATHELTQKMAKVLLAQESRAERGSKKTPPGKGRPPLGKNQCAYCKEEGHWKKNCPKLVSGA TPVLVEELQ Protective antigen VP22 Gallid herpesvirus 2 strain CVI988/Rispens 33090005 CDD:309800 10390 ? VP22 10.7 26320.06 293 Herpesvirus UL49 tegument protein; pfam04823 >AAP93873.1 VP22 [Gallid alphaherpesvirus 2] MGDSERRKSERRRSLGYPSAYDDVSIPARRPSTRTQRNLNQDDLSKHGPFTDHPTQKYKSAKAVSEDVSS TTRGGFTNKPRAKPGVRAVQSNKFAFSTAPSSASSTWRSNTVAFNQRMFCGAVATVAQYHAYQGALALWR QDPPRTNEELDAFLSRAVIKITIQEGPNLMGEAETCARKLLEESGLSQGNENVKSKSERTRRGGEIEIKS PDPGSHRTHNPRTPATSRRHHSSARGYRGSDSE Protective antigen