# US 2014/0154265 A1 · Arterivirus > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2014/0154265 A1 - Document ID: US20140154265A1 - Status: Published application - Kind: A1 - Application number: 14/035,415 - Filed: 2013-09-24 - Published: 2014-06-05 - Earliest claimed: 2012-09-26 - Assignees: University of Manitoba - Inventors: Marjolein Kikkert; Brian Leonard Mark; Puck Bertyne van Kasteren; Terrence William James; Eric John Snijder - Web page: https://patentgrep.com/patent/US20140154265A1 ## CPC - A61K 39/12: Viral antigens - A61K 39/02: Bacterial antigens - A61K 39/40: bacterial - A61K 39/42: viral - A61P 31/00: Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics - A61P 31/04: Antibacterial agents - A61P 31/14: for RNA viruses - A61P 31/16: for influenza or rhinoviruses - A61P 31/20: for DNA viruses - A61P 31/22: for herpes viruses - C12N 7/00: Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof (preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00) - A61K 2039/5254: {avirulent or attenuated} - A61K 2039/552: {Veterinary vaccine} - C07K 2299/00: Coordinates from 3D structures of peptides, e.g. proteins or enzymes - C12N 2770/10021: Viruses as such, e.g. new isolates, mutants or their genomic sequences - C12N 2770/10034: Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein - C12N 2770/10062: by genetic engineering - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00) - C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00) ## Abstract The present invention relates to replication-competent Arteriviruses having a decreased DUB/deISGylating activity due to a mutation in the PLP2 domain of the non-structural protein nsp2, to their use as a medicament, their use as a vaccine and in prophylaxis, to vaccines comprising such Arteriviruses and to Arteriviral PLP2-ubiquitin complexes. ## Claims ### Claim 1 A replication-competent Arterivirus, characterized in that said virus has a decreased DUB/deISGylating activity due to a mutation in the PLP2 domain of the non-structural protein nsp2. ### Claim 2 (depends on 1) A replication-competent Arterivirus according to claim 1, characterised in that said Arterivirus is selected from the group of viruses consisting of Equine arteritis virus (EAV) and Porcine respiratory and reproductive syndrome virus (PRRSV). ### Claim 3 (depends on 1) A replication-competent Arterivirus according to claim 1, characterised in that said mutation in the PLP2 domain is located at any of consensus positions 296-297 and/or 303-306 and/or 309-319 and/or 326-330 and/or 343-355 according to the EAV numbering as depicted in FIG. 3. ### Claim 4 (depends on 3) A replication-competent Arterivirus according to claim 3, characterized in that said mutation in the PLP2 domain is located at any of consensus positions position 296-297 and/or 303-306 and/or 310-318 and/or 327-329 and/or 343-354 according to the EAV numbering as depicted in FIG. 3. ### Claim 5 (depends on 4) A replication-competent Arterivirus according to claim 4, characterized in that said mutation in the PLP2 domain is located at consensus positions 296-297 and/or 303-306 and/or 311-317 and/or 328 and/or 343-346 and/or 347-348 and/or 350-353 according to the EAV numbering as depicted in FIG. 3. ### Claim 6 (depends on 5) A replication-competent Arterivirus according to claim 5, characterized in that said mutation in the PLP2 domain is at consensus position T312, I313 or I353. ### Claim 7 (depends on 6) A replication-competent Arterivirus according to claim 6, characterized in that said Arterivirus is EAV and said mutation in the PLP2 domain is T312A, I313V, I353A, I353R, I353S, I353T or I353W. ### Claim 8 (depends on 1) A replication-competent Arterivirus according to claim 1, characterized in that said virus comprises at least 2 mutations, each of which contributes to a decreased DUB/deISGylating activity. ### Claim 9 (depends on 1) A vaccine for the protection of mammals against Arteriviral infection, characterized in that said vaccine comprises the replication-competent Arterivirus of claim 1, and a pharmaceutically acceptable carrier. ### Claim 10 (depends on 8) A vaccine for the protection of mammals against Arteriviral infection, characterized in that said vaccine comprises a replication-competent Arterivirus according to claim 8, and a pharmaceutically acceptable carrier. ### Claim 11 (depends on 9) A vaccine according to claim 9, characterized in that said vaccine comprises an additional immunogen of a virus or micro-organism pathogenic to the animal to be vaccinated, an antibody against said immunogen or genetic information encoding an immunogen of said virus or micro-organism. ### Claim 12 (depends on 10) A vaccine according to claim 10, characterized in that said vaccine comprises an additional immunogen of a virus or micro-organism pathogenic to the animal to be vaccinated, an antibody against said immunogen or genetic information encoding an immunogen of said virus or micro-organism. ### Claim 13 (depends on 11) A vaccine according to claim 11, characterized in that said the virus or micro-organism pathogenic to the animal to be vaccinated is selected from the group of Brachyspira hyodysenteriae, African Swine Fever virus, Nipah virus, Porcine Circovirus, Porcine Torque Teno virus, Pseudorabies virus, Porcine influenza virus, Porcine Epidemic Diarrheal virus (PEDV), Foot and Mouth disease virus, Transmissible gastro-enteritis virus, Rotavirus, Escherichia coli, Erysipelo rhusiopathiae, Bordetella bronchiseptica, Salmonella cholerasuis, Haemophilus parasuis, Pasteurella multocida, Streptococcus suis, Mycoplasma hyopneumoniae and Actinobacillus pleuropneumoniae. ### Claim 14 (depends on 12) A vaccine according to claim 12, characterized in that said the virus or micro-organism pathogenic to the animal to be vaccinated is selected from the group of Brachyspira hyodysenteriae, African Swine Fever virus, Nipah virus, Porcine Circovirus, Porcine Torque Teno virus, Pseudorabies virus, Porcine influenza virus, Porcine Epidemic Diarrheal virus (PEDV), Foot and Mouth disease virus, Transmissible gastro-enteritis virus, Rotavirus, Escherichia coli, Erysipelo rhusiopathiae, Bordetella bronchiseptica, Salmonella cholerasuis, Haemophilus parasuis, Pasteurella multocida, Streptococcus suis, Mycoplasma hyopneumoniae and Actinobacillus pleuropneumoniae. ### Claim 15 (depends on 11) A vaccine according to claim 11, characterized in that said the virus or micro-organism pathogenic to the animal to be vaccinated is selected from the group consisting of Equine Influenza virus, Clostridium tetani, Equine Herpesvirus 1 and Equine Herpesvirus 4. ### Claim 16 (depends on 12) A vaccine according to claim 12, characterized in that said the virus or micro-organism pathogenic to the animal to be vaccinated is selected from the group consisting of Equine Influenza virus, Clostridium tetani, Equine Herpesvirus 1 and Equine Herpesvirus 4. ### Claim 17 A PLP2-ubiquitin complex comprising ubiquitin and at least the PLP2 domain of nsp2 of an Arterivirus, wherein said PLP2 domain is covalently bound to said ubiquitin, or a PLP2-ISG15 complex comprising ISG15 and at least the PLP2 domain of nsp2 of an Arterivirus, wherein said PLP2 domain is covalently bound to said ISG15. ### Claim 18 (depends on 17) A PLP2-ubiquitin complex or PLP2-ISG15 complex according to claim 17, characterized in that said Arterivirus is selected from the group of viruses consisting of EAV and PRRSV. ### Claim 19 (depends on 1) A method of providing prophylaxis for an Arteriviral infection in a mammal comprising administering to said animal the replication-competent Arterivirus of claim 1. ### Claim 20 (depends on 8) A method of providing prophylaxis for an Arteriviral infection in a mammal comprising administering the replication-competent Arterivirus of claim 8.