Protegen ID Gene Name Sequence Strain (Species/Organism) NCBI Gene ID NCBI Nucleotide GI NCBI Protein GI Locus Tag Genbank Accession Protein Accession Protein Name Protein Annotation Molecule Role Molecule Role Annotation COG PMID 1909 C12L Vaccinia virus 3707582 66276002 VACWR205 YP_233087.1 temporal expression: early Virulence factor MUTATION: C12L mutant is attenuated in BALB/c mice when infected intranasally [Ref6598:Symons et al., 2002]. 12388820 1910 E3L Vaccinia virus 3707592 66275856 VACWR059 YP_232941.1 temporal expression: early Virulence factor MUTATION: VVDeltaE3L mutant is apathogenic in mice [Ref6599:Brandt and Jacobs, 2001]. 11134298 1911 N1L Vaccinia virus 3707643 66275825 VACWR028 YP_232910.1 temporal expression: early/late Virulence factor MUTATION: Deletion of N1L results in attenuation in culture and in intracranially infected mice [Ref6600:Cheltsov et al., 2010]. 20441222 1912 A35R Vaccinia virus 3707688 66275955 VACWR158 YP_233040.1 hypothetical protein Virulence factor MUTATION: vA35R deletion mutant was attenuated in intranasal challenge of mice compared to the wild-type virus [Ref6601:Roper, 2006]. ; 16352555 1913 A46R Vaccinia virus 3707702 66275969 VACWR172 YP_233054.1 Toll/IL1-receptor Virulence factor MUTATION: Vaccinia virus lacking the A46R gene was attenuated in a murine intranasal model [Ref6602:Stack et al., 2005]. 15767367 4828 B14R Vaccinia virus 335308 B14R 17.3K protein Virulence factor MUTATION: B14 deletion mutant is attenuated in C57BL6 mice infected intradermally [Ref7255:Chen et al., 2006].; 16690909 5020 F12L Vaccinia virus 3707508 66275848 VACWR051 AY243312 YP_232933 EEV maturation protein Virulence factor The vDeltaF12L virus was severely attenuated in vivo, such that a dose of vDeltaF12L 10,000-fold greater than the dose of wild-type virus that induced severe disease was unable to induce disease in mice infected intranasally [Ref7425:Zhang et al., 2000]. 11090164 5021 TI4L Vaccinia virus (strain Tian Tan) 6969720 TI4L Virulence factor 5029 VACVgp007 Vaccinia virus 1486315 9790910 VACVgp007 NP_063637 Hypothetical protein Virulence factor Skin lesions caused by the C21L deletion mutant were smaller than those caused by wild-type virus, demonstrating an important role for VCP in virulence. The C21L deletion mutant also was attenuated in C4-deficient guinea pigs. [Ref7433:Isaacs et al., 1992] 1731333 5035 VGF Cowpox virus 1485896 20178389 CPXV021 AF482758 NP_619810 CPXV021 protein or CPXV VGF protein Virulence factor MUTATION: Higher doses of VGF- virus than WT virus were required for intracranial lethality in mice and for production of skin lesions in rabbits. Thus, expression of the VGF gene is important to the virulence of vaccinia virus [Ref7439:Buller et al., 1988]. 3339716 5037 B5R Vaccinia virus 3707658 66275984 VACWR187 A22016 YP_233069 EEV membrane glycoprotein Virulence factor only 10% of WT levels of EEV were produced by I-delta B5R. deletion of B5R had a profound affect on the formation of the extracellular enveloped virus (EEV). shown to form very small plaques compared with the wild-type viruses. [Ref7441:Engelstad and Smith, 1993] 8503178 5038 A36R Vaccinia virus 3707689 66275956 VACWR159 X57318 YP_233041 IEV transmembrane phosphoprotein Virulence factor Thus the loss of the A36R protein from the EEV surface did not reduce EEV specific infectivity in vitro. Despite this, delta A36R showed striking attenuation compared with WT in a murine intranasal model. [Ref7443:Parkinson and Smith, 1994] 8091668 5039 A34R Vaccinia virus 3707687 66275954 VACWR157 JN654979 YP_233039 IEV and EEV membrane glycoprotein Virulence factor The WR delta A34R virus is highly attenuated in vivo compared with WR or a revertant virus in which the A34R gene was reinserted into WR delta A34R. [Ref7444:McIntosh and Smith, 1996] 8523536 5040 B7R Vaccinia virus 3707660 66275986 VACWR189 M58056 YP_233071 hypothetical protein Virulence factor A virus deletion mutant lacking the B7R gene and a revertant virus were constructed. Compared to wild-type and revertant viruses, the deletion mutant replicated normally in cell culture and had unaltered virulence in a murine intranasal model of infection. However, the deletion mutant was attenuated in a murine intradermal model where it induced a smaller lesion than the control viruses. [Ref7445:Price et al., 2000] 10648184 5041 H3L Vaccinia virus 3707557 66275898 VACWR101 AY243312 YP_232983 IMV heparin binding surface protein Virulence factor mice infected with H3L(-) mutant virus survive and recover faster, indicating that inactivation of the H3L gene attenuates virus virulence in vivo. [Ref7446:Lin et al., 2000] 10708453 5042 B8R Vaccinia virus 3707661 66275987 VACWR190 AF120160 YP_233072 soluble interferon-gamma receptor-like protein Virulence factor In rabbits, skin lesions produced by the WR B8R-deleted mutants were smaller and tended to disappear earlier than those caused by wild-type WR virus. Similar results were obtained with both independently prepared WR B8R-deleted mutants. These data strongly suggested that the product of B8R gene did play a role in virus virulence. [Ref7447:Sroller et al., 2001] 11315635 5043 A14.5L Vaccinia virus 3707532 66275931 VACWR134 JN654977 YP_233016 hydrophobic IMV membrane protein Virulence factor A mutant virus, in which the A14.5L ORF was largely deleted, produced normal-size plaques in several cell lines, and the yields of infectious intra- and extracellular viruses were similar to those of the parent. In contrast, with a mouse model, mutant viruses with the A14.5L ORF largely deleted were attenuated relative to that of the parental virus or a mutant virus with a restored A14.5L gene. [Ref7448:Betakova et al., 2000] 10756020 5044 Uracil DNA glycosylase (D4R/D5R) 402497 Virulence factor MUTATION: The conservation of the catalytic site in all poxvirus orthologs suggested an important role in vivo. This idea was confirmed by the decreased virulence of catalytic-site mutants when administered by the intranasal route to mice [Ref7449:De and Moss, 2003]. 12477821 5045 A53R Vaccinia virus 3707710 66275976 VACWR179 M58054 YP_233061 secreted TNF-receptor-like protein Virulence factor we constructed C12L (vIL-18 binding protein) and A53R (vTNF receptor homolog) gene-deleted mutants which are based on parental TV and VTKgpe (TV expressing HIV gagpol and env gene), respectively. The pathogenicity and immunogenicity were also evaluated. Deleting these two immunomodulatory genes lessened the virulence of the parental virus in both mice and rabbit models. Notably, C12L deletion mutant attenuated the skin virulence of parental virus by as high as approximate 2 logs. [Ref7450:Dai et al., 2008] 18573290 5046 A43R Vaccinia virus 3707698 66275965 VACWR168 M72474 YP_233050 putative type-I membrane glycoprotein Virulence factor Prevention of A43R expression had no effect on plaque size or virus replication in cell culture and little effect on virulence after mouse intranasal infection. Although the A43 mutant produced significantly smaller lesions in skin of mice than the control, the amounts of virus recovered from the lesions were similar. [Ref7451:Sood and Moss, 2010] 19900687 5047 C6L 137539 Protein C6 Virulence factor Mutant viruses in which the C6L gene is deleted, or mutated so that the C6 protein is not expressed, replicated normally in cell culture but were attenuated in two in vivo models of infection compared to wild type and revertant controls. [Ref7452:Unterholzner et al., 2011] 21931555 5048 J2R Vaccinia virus 3707550 66275891 VACWR094 JN654986 YP_232976 thymidine kinase Virulence factor We have shown that insertion of the three vaccinia virus (VACV) promoter-driven foreign gene expression cassettes encoding Renilla luciferase-Aequorea GFP fusion protein, β-galactosidase, and β-glucuronidase into the F14.5L, J2R, and A56R loci of the VACV LIVP genome, respectively, results in a highly attenuated mutant strain GLV-1h68. This strain shows tumor-specific replication and is capable of eradicating tumors with little or no virulence in mice. [Ref7453:Chen et al., 2011] 21951588 5049 A56R Vaccinia virus 3707652 66275978 VACWR181 M93956 YP_233063 hemagglutinin Virulence factor We have shown that insertion of the three vaccinia virus (VACV) promoter-driven foreign gene expression cassettes encoding Renilla luciferase-Aequorea GFP fusion protein, β-galactosidase, and β-glucuronidase into the F14.5L, J2R, and A56R loci of the VACV LIVP genome, respectively, results in a highly attenuated mutant strain GLV-1h68. This strain shows tumor-specific replication and is capable of eradicating tumors with little or no virulence in mice. [Ref7453:Chen et al., 2011] 21951588 5050 O1L Vaccinia virus 3707601 66275865 VACWR068 AY243312 YP_232950 Hypothetical protein Virulence factor CVA-ΔO1L showed reduced plaque size and an attenuated cytopathic effect (CPE) in infected cell cultures and reduced virulence and spread from lungs to ovaries in intranasally infected BALB/c mice. [Ref7454:Schweneker et al., 2012] 22171261 5051 N2L Vaccinia virus 3707644 66275826 VACWR029 M22812 YP_232911 putative alpha aminitin-sensitive protein Virulence factor A mutant VACV strain Western Reserve lacking the N2L gene (vΔN2) showed normal replication and spread in cultured cells compared to wild-type parental (vN2) and revertant (vN2-rev) viruses, but was attenuated in two murine models of infection. After intranasal infection, the vΔN2 mutant induced lower weight loss and signs of illness, and virus was cleared more rapidly from the infected tissue. In the intradermal model of infection, vΔN2 induced smaller lesions that were resolved more rapidly. In summary, the N2 protein is an intracellular virulence factor that inhibits IRF3 activity in the nucleus. [Ref7455:Ferguson et al., 2013] 23761407 5052 TE3L 6969701 TE3L Virulence factor The results suggested that deletion of the TE3L gene decreased the virulence and neurovirulence significantly in mice and rabbit models, yet retained the immunogenicity. Thus, the deletion of TE3L improved the safety of the VTT vector; this approach may yield a valuable resource for studies of recombinant VACV-vectored vaccines. [Ref7456:Wang et al., 2012] 23084929 5053 D10R Vaccinia virus 3707571 66275912 VACWR115 M15058 YP_232997 contains mutT-like motif of NTP-phosphohydrolase for DNA repair Virulence factor Despite the mild effects in vitro, both mutants were more attenuated than the revertants in intranasal and intraperitoneal mouse models, and less infectious virus was recovered from organs. In addition, there was less lung histopathology following intranasal infection with mutant viruses. [Ref7457:Liu et al., 2014] 24155373 5106 F14.5L Vaccinia virus 4557754 119223229 VACWR053.5 M57977 YP_910497 hypothetical protein Virulence factor We have shown that insertion of the three vaccinia virus (VACV) promoter-driven foreign gene expression cassettes encoding Renilla luciferase-Aequorea GFP fusion protein, β-galactosidase, and β-glucuronidase into the F14.5L, J2R, and A56R loci of the VACV LIVP genome, respectively, results in a highly attenuated mutant strain GLV-1h68. This strain shows tumor-specific replication and is capable of eradicating tumors with little or no virulence in mice. [Ref7453:Chen et al., 2011]; 21951588