Precision engineering for PRRSV resistance in pigs: Macrophages from genome edited pigs lacking CD163 SRCR5 domain are fully resistant to both PRRSV genotypes while maintaining biological function
Porcine Reproductive and Respiratory Syndrome (PRRS) is a panzootic infectious disease of pigs, causing major economic losses to the world-wide pig industry. PRRS manifests differently in pigs of all ages but primarily causes late-term abortions and stillbirths in sows and respiratory disease in pig...
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| description | Porcine Reproductive and Respiratory Syndrome (PRRS) is a panzootic infectious disease of pigs, causing major economic losses to the world-wide pig industry. PRRS manifests differently in pigs of all ages but primarily causes late-term abortions and stillbirths in sows and respiratory disease in piglets. The causative agent of the disease is the positive-strand RNA PRRS virus (PRRSV). PRRSV has a narrow host cell tropism, limited to cells of the monocyte/macrophage lineage. CD163 has been described as a fusion receptor for PRRSV, whereby the scavenger receptor cysteine-rich domain 5 (SRCR5) region was shown to be an interaction site for the virus in vitro. CD163 is expressed at high levels on the surface of macrophages, particularly in the respiratory system. Here we describe the application of CRISPR/Cas9 to pig zygotes, resulting in the generation of pigs with a deletion of Exon 7 of the CD163 gene, encoding SRCR5. Deletion of SRCR5 showed no adverse effects in pigs maintained under standard husbandry conditions with normal growth rates and complete blood counts observed. Pulmonary alveolar macrophages (PAMs) and peripheral blood monocytes (PBMCs) were isolated from the animals and assessed in vitro. Both PAMs and macrophages obtained from PBMCs by CSF1 stimulation (PMMs) show the characteristic differentiation and cell surface marker expression of macrophages of the respective origin. Expression and correct folding of the SRCR5 deletion CD163 on the surface of macrophages and biological activity of the protein as hemoglobin-haptoglobin scavenger was confirmed. Challenge of both PAMs and PMMs with PRRSV genotype 1, subtypes 1, 2, and 3 and PMMs with PRRSV genotype 2 showed complete resistance to viral infections assessed by replication. Confocal microscopy revealed the absence of replication structures in the SRCR5 CD163 deletion macrophages, indicating an inhibition of infection prior to gene expression, i.e. at entry/fusion or unpacking stages. |
| doi_str_mv | 10.1371/journal.ppat.1006206 |
| format | Article |
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PRRS manifests differently in pigs of all ages but primarily causes late-term abortions and stillbirths in sows and respiratory disease in piglets. The causative agent of the disease is the positive-strand RNA PRRS virus (PRRSV). PRRSV has a narrow host cell tropism, limited to cells of the monocyte/macrophage lineage. CD163 has been described as a fusion receptor for PRRSV, whereby the scavenger receptor cysteine-rich domain 5 (SRCR5) region was shown to be an interaction site for the virus in vitro. CD163 is expressed at high levels on the surface of macrophages, particularly in the respiratory system. Here we describe the application of CRISPR/Cas9 to pig zygotes, resulting in the generation of pigs with a deletion of Exon 7 of the CD163 gene, encoding SRCR5. Deletion of SRCR5 showed no adverse effects in pigs maintained under standard husbandry conditions with normal growth rates and complete blood counts observed. Pulmonary alveolar macrophages (PAMs) and peripheral blood monocytes (PBMCs) were isolated from the animals and assessed in vitro. Both PAMs and macrophages obtained from PBMCs by CSF1 stimulation (PMMs) show the characteristic differentiation and cell surface marker expression of macrophages of the respective origin. Expression and correct folding of the SRCR5 deletion CD163 on the surface of macrophages and biological activity of the protein as hemoglobin-haptoglobin scavenger was confirmed. Challenge of both PAMs and PMMs with PRRSV genotype 1, subtypes 1, 2, and 3 and PMMs with PRRSV genotype 2 showed complete resistance to viral infections assessed by replication. Confocal microscopy revealed the absence of replication structures in the SRCR5 CD163 deletion macrophages, indicating an inhibition of infection prior to gene expression, i.e. at entry/fusion or unpacking stages.</description><identifier>ISSN: 1553-7374</identifier><identifier>ISSN: 1553-7366</identifier><identifier>EISSN: 1553-7374</identifier><identifier>DOI: 10.1371/journal.ppat.1006206</identifier><identifier>PMID: 28231264</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Abortion ; Animals ; Antigens, CD - genetics ; Antigens, Differentiation, Myelomonocytic - genetics ; Biology and Life Sciences ; Biomedical engineering ; Blotting, Western ; Flow Cytometry ; Fluorescent Antibody Technique ; Funding ; Gene Editing - methods ; Gene expression ; Genetic aspects ; Genome ; Genomes ; Genotype ; Genotype & phenotype ; Genotypes ; Health aspects ; Hogs ; Identification and classification ; Infections ; Infectious diseases ; Macrophages - immunology ; Macrophages - metabolism ; Macrophages - virology ; Medicine and Health Sciences ; Microscopy, Confocal ; Polymerase Chain Reaction ; Porcine reproductive and respiratory syndrome ; Porcine Reproductive and Respiratory Syndrome - immunology ; Porcine respiratory and reproductive syndrome virus - immunology ; Receptors, Cell Surface - deficiency ; Receptors, Cell Surface - genetics ; Research and Analysis Methods ; Respiratory diseases ; Respiratory system ; Risk factors ; Studies ; Swine ; Viral infections</subject><ispartof>PLoS pathogens, 2017-02, Vol.13 (2), p.e1006206-e1006206</ispartof><rights>COPYRIGHT 2017 Public Library of Science</rights><rights>2017 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Burkard C, Lillico SG, Reid E, Jackson B, Mileham AJ, Ait-Ali T, et al. (2017) Precision engineering for PRRSV resistance in pigs: Macrophages from genome edited pigs lacking CD163 SRCR5 domain are fully resistant to both PRRSV genotypes while maintaining biological function. PLoS Pathog 13(2): e1006206. doi:10.1371/journal.ppat.1006206</rights><rights>2017 Burkard et al 2017 Burkard et al</rights><rights>2017 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Burkard C, Lillico SG, Reid E, Jackson B, Mileham AJ, Ait-Ali T, et al. (2017) Precision engineering for PRRSV resistance in pigs: Macrophages from genome edited pigs lacking CD163 SRCR5 domain are fully resistant to both PRRSV genotypes while maintaining biological function. PLoS Pathog 13(2): e1006206. doi:10.1371/journal.ppat.1006206</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c727t-9b854766b7c90749cbf32830668570df918a3a4af0705a961d60e4e65390cccf3</citedby><cites>FETCH-LOGICAL-c727t-9b854766b7c90749cbf32830668570df918a3a4af0705a961d60e4e65390cccf3</cites><orcidid>0000-0003-4806-0902 ; 0000-0001-9213-1830 ; 0000-0002-5101-2277 ; 0000-0002-0471-3230</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5322883/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5322883/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28231264$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Burkard, Christine</creatorcontrib><creatorcontrib>Lillico, Simon G</creatorcontrib><creatorcontrib>Reid, Elizabeth</creatorcontrib><creatorcontrib>Jackson, Ben</creatorcontrib><creatorcontrib>Mileham, Alan J</creatorcontrib><creatorcontrib>Ait-Ali, Tahar</creatorcontrib><creatorcontrib>Whitelaw, C Bruce A</creatorcontrib><creatorcontrib>Archibald, Alan L</creatorcontrib><title>Precision engineering for PRRSV resistance in pigs: Macrophages from genome edited pigs lacking CD163 SRCR5 domain are fully resistant to both PRRSV genotypes while maintaining biological function</title><title>PLoS pathogens</title><addtitle>PLoS Pathog</addtitle><description>Porcine Reproductive and Respiratory Syndrome (PRRS) is a panzootic infectious disease of pigs, causing major economic losses to the world-wide pig industry. PRRS manifests differently in pigs of all ages but primarily causes late-term abortions and stillbirths in sows and respiratory disease in piglets. The causative agent of the disease is the positive-strand RNA PRRS virus (PRRSV). PRRSV has a narrow host cell tropism, limited to cells of the monocyte/macrophage lineage. CD163 has been described as a fusion receptor for PRRSV, whereby the scavenger receptor cysteine-rich domain 5 (SRCR5) region was shown to be an interaction site for the virus in vitro. CD163 is expressed at high levels on the surface of macrophages, particularly in the respiratory system. Here we describe the application of CRISPR/Cas9 to pig zygotes, resulting in the generation of pigs with a deletion of Exon 7 of the CD163 gene, encoding SRCR5. Deletion of SRCR5 showed no adverse effects in pigs maintained under standard husbandry conditions with normal growth rates and complete blood counts observed. Pulmonary alveolar macrophages (PAMs) and peripheral blood monocytes (PBMCs) were isolated from the animals and assessed in vitro. Both PAMs and macrophages obtained from PBMCs by CSF1 stimulation (PMMs) show the characteristic differentiation and cell surface marker expression of macrophages of the respective origin. Expression and correct folding of the SRCR5 deletion CD163 on the surface of macrophages and biological activity of the protein as hemoglobin-haptoglobin scavenger was confirmed. Challenge of both PAMs and PMMs with PRRSV genotype 1, subtypes 1, 2, and 3 and PMMs with PRRSV genotype 2 showed complete resistance to viral infections assessed by replication. Confocal microscopy revealed the absence of replication structures in the SRCR5 CD163 deletion macrophages, indicating an inhibition of infection prior to gene expression, i.e. at entry/fusion or unpacking stages.</description><subject>Abortion</subject><subject>Animals</subject><subject>Antigens, CD - genetics</subject><subject>Antigens, Differentiation, Myelomonocytic - genetics</subject><subject>Biology and Life Sciences</subject><subject>Biomedical engineering</subject><subject>Blotting, Western</subject><subject>Flow Cytometry</subject><subject>Fluorescent Antibody Technique</subject><subject>Funding</subject><subject>Gene Editing - methods</subject><subject>Gene expression</subject><subject>Genetic aspects</subject><subject>Genome</subject><subject>Genomes</subject><subject>Genotype</subject><subject>Genotype & phenotype</subject><subject>Genotypes</subject><subject>Health aspects</subject><subject>Hogs</subject><subject>Identification and classification</subject><subject>Infections</subject><subject>Infectious diseases</subject><subject>Macrophages - immunology</subject><subject>Macrophages - metabolism</subject><subject>Macrophages - virology</subject><subject>Medicine and Health Sciences</subject><subject>Microscopy, Confocal</subject><subject>Polymerase Chain Reaction</subject><subject>Porcine reproductive and respiratory syndrome</subject><subject>Porcine Reproductive and Respiratory Syndrome - immunology</subject><subject>Porcine respiratory and reproductive syndrome virus - immunology</subject><subject>Receptors, Cell Surface - deficiency</subject><subject>Receptors, Cell Surface - genetics</subject><subject>Research and Analysis Methods</subject><subject>Respiratory diseases</subject><subject>Respiratory system</subject><subject>Risk factors</subject><subject>Studies</subject><subject>Swine</subject><subject>Viral infections</subject><issn>1553-7374</issn><issn>1553-7366</issn><issn>1553-7374</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqVk81u1DAQgCMEoqXwBggscYHDLnbs2AkHpGr5q1Sg2gJXy3EmWZfEDrYX6PvxYDhtWnVRLyiKEsXffDNjZ7LsMcFLQgV5eea23qp-OY4qLgnGPMf8TrZPioIuBBXs7o33vexBCGcYM0IJv5_t5WVOSc7ZfvbnxIM2wTiLwHbGAnhjO9Q6j07W69NvyEMwISqrARmLRtOFV-ij0t6NG9VBQK13A-rAugEQNCZCcwGhXunvk2n1hnCKTterdYEaN6gkUR5Qu-3782t5RNGh2sXNnHTyxfMx6X9tTA9oCovpnoS1cb3rjFZ9klgdU-kPs3ut6gM8mp8H2dd3b7-sPiyOP78_Wh0eL7TIRVxUdVkwwXktdIUFq3Td0rykmPOyELhpK1IqqphqscCFqjhpOAYGvKAV1lq39CB7eukdexfkfABBklKUWOSsook4uiQap87k6M2g_Ll0ysiLD853UvlodA9S01oxhnGpc8YqXqmcYEhViKYqySQ7yF7P2bb1AI0GG73qd6S7K9ZsZOd-yoLmeVlOxTyfBd792EKIcjBBQ98rC257UXdeiNQ8Tuizf9Dbu5upTqUGjG1dyqsnqTxM6yXhTJBELW-h0tXAYLSz0KYj3Q14sROQmAi_Y6e2Icij0_V_sJ92WXbJpr81BA_t9d4RLKcZumpSTjMk5xlKYU9u7vt10NXQ0L-vdBjK</recordid><startdate>20170223</startdate><enddate>20170223</enddate><creator>Burkard, Christine</creator><creator>Lillico, Simon G</creator><creator>Reid, Elizabeth</creator><creator>Jackson, Ben</creator><creator>Mileham, Alan J</creator><creator>Ait-Ali, Tahar</creator><creator>Whitelaw, C Bruce A</creator><creator>Archibald, Alan L</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>ISN</scope><scope>ISR</scope><scope>3V.</scope><scope>7QL</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0003-4806-0902</orcidid><orcidid>https://orcid.org/0000-0001-9213-1830</orcidid><orcidid>https://orcid.org/0000-0002-5101-2277</orcidid><orcidid>https://orcid.org/0000-0002-0471-3230</orcidid></search><sort><creationdate>20170223</creationdate><title>Precision engineering for PRRSV resistance in pigs: Macrophages from genome edited pigs lacking CD163 SRCR5 domain are fully resistant to both PRRSV genotypes while maintaining biological function</title><author>Burkard, Christine ; Lillico, Simon G ; Reid, Elizabeth ; Jackson, Ben ; Mileham, Alan J ; Ait-Ali, Tahar ; Whitelaw, C Bruce A ; Archibald, Alan L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c727t-9b854766b7c90749cbf32830668570df918a3a4af0705a961d60e4e65390cccf3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Abortion</topic><topic>Animals</topic><topic>Antigens, CD - 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immunology</topic><topic>Porcine respiratory and reproductive syndrome virus - immunology</topic><topic>Receptors, Cell Surface - deficiency</topic><topic>Receptors, Cell Surface - genetics</topic><topic>Research and Analysis Methods</topic><topic>Respiratory diseases</topic><topic>Respiratory system</topic><topic>Risk factors</topic><topic>Studies</topic><topic>Swine</topic><topic>Viral infections</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Burkard, Christine</creatorcontrib><creatorcontrib>Lillico, Simon G</creatorcontrib><creatorcontrib>Reid, Elizabeth</creatorcontrib><creatorcontrib>Jackson, Ben</creatorcontrib><creatorcontrib>Mileham, Alan J</creatorcontrib><creatorcontrib>Ait-Ali, Tahar</creatorcontrib><creatorcontrib>Whitelaw, C Bruce A</creatorcontrib><creatorcontrib>Archibald, Alan L</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Canada</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PLoS pathogens</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Burkard, Christine</au><au>Lillico, Simon G</au><au>Reid, Elizabeth</au><au>Jackson, Ben</au><au>Mileham, Alan J</au><au>Ait-Ali, Tahar</au><au>Whitelaw, C Bruce A</au><au>Archibald, Alan L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Precision engineering for PRRSV resistance in pigs: Macrophages from genome edited pigs lacking CD163 SRCR5 domain are fully resistant to both PRRSV genotypes while maintaining biological function</atitle><jtitle>PLoS pathogens</jtitle><addtitle>PLoS Pathog</addtitle><date>2017-02-23</date><risdate>2017</risdate><volume>13</volume><issue>2</issue><spage>e1006206</spage><epage>e1006206</epage><pages>e1006206-e1006206</pages><issn>1553-7374</issn><issn>1553-7366</issn><eissn>1553-7374</eissn><abstract>Porcine Reproductive and Respiratory Syndrome (PRRS) is a panzootic infectious disease of pigs, causing major economic losses to the world-wide pig industry. PRRS manifests differently in pigs of all ages but primarily causes late-term abortions and stillbirths in sows and respiratory disease in piglets. The causative agent of the disease is the positive-strand RNA PRRS virus (PRRSV). PRRSV has a narrow host cell tropism, limited to cells of the monocyte/macrophage lineage. CD163 has been described as a fusion receptor for PRRSV, whereby the scavenger receptor cysteine-rich domain 5 (SRCR5) region was shown to be an interaction site for the virus in vitro. CD163 is expressed at high levels on the surface of macrophages, particularly in the respiratory system. Here we describe the application of CRISPR/Cas9 to pig zygotes, resulting in the generation of pigs with a deletion of Exon 7 of the CD163 gene, encoding SRCR5. Deletion of SRCR5 showed no adverse effects in pigs maintained under standard husbandry conditions with normal growth rates and complete blood counts observed. Pulmonary alveolar macrophages (PAMs) and peripheral blood monocytes (PBMCs) were isolated from the animals and assessed in vitro. Both PAMs and macrophages obtained from PBMCs by CSF1 stimulation (PMMs) show the characteristic differentiation and cell surface marker expression of macrophages of the respective origin. Expression and correct folding of the SRCR5 deletion CD163 on the surface of macrophages and biological activity of the protein as hemoglobin-haptoglobin scavenger was confirmed. Challenge of both PAMs and PMMs with PRRSV genotype 1, subtypes 1, 2, and 3 and PMMs with PRRSV genotype 2 showed complete resistance to viral infections assessed by replication. Confocal microscopy revealed the absence of replication structures in the SRCR5 CD163 deletion macrophages, indicating an inhibition of infection prior to gene expression, i.e. at entry/fusion or unpacking stages.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>28231264</pmid><doi>10.1371/journal.ppat.1006206</doi><orcidid>https://orcid.org/0000-0003-4806-0902</orcidid><orcidid>https://orcid.org/0000-0001-9213-1830</orcidid><orcidid>https://orcid.org/0000-0002-5101-2277</orcidid><orcidid>https://orcid.org/0000-0002-0471-3230</orcidid><oa>free_for_read</oa></addata></record> |
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| source | Public Library of Science (PLoS) Journals Open Access; MEDLINE; DOAJ Directory of Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central; PubMed Central Open Access |
| subjects | Abortion Animals Antigens, CD - genetics Antigens, Differentiation, Myelomonocytic - genetics Biology and Life Sciences Biomedical engineering Blotting, Western Flow Cytometry Fluorescent Antibody Technique Funding Gene Editing - methods Gene expression Genetic aspects Genome Genomes Genotype Genotype & phenotype Genotypes Health aspects Hogs Identification and classification Infections Infectious diseases Macrophages - immunology Macrophages - metabolism Macrophages - virology Medicine and Health Sciences Microscopy, Confocal Polymerase Chain Reaction Porcine reproductive and respiratory syndrome Porcine Reproductive and Respiratory Syndrome - immunology Porcine respiratory and reproductive syndrome virus - immunology Receptors, Cell Surface - deficiency Receptors, Cell Surface - genetics Research and Analysis Methods Respiratory diseases Respiratory system Risk factors Studies Swine Viral infections |
| title | Precision engineering for PRRSV resistance in pigs: Macrophages from genome edited pigs lacking CD163 SRCR5 domain are fully resistant to both PRRSV genotypes while maintaining biological function |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-07T20%3A21%3A14IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Precision%20engineering%20for%20PRRSV%20resistance%20in%20pigs:%20Macrophages%20from%20genome%20edited%20pigs%20lacking%20CD163%20SRCR5%20domain%20are%20fully%20resistant%20to%20both%20PRRSV%20genotypes%20while%20maintaining%20biological%20function&rft.jtitle=PLoS%20pathogens&rft.au=Burkard,%20Christine&rft.date=2017-02-23&rft.volume=13&rft.issue=2&rft.spage=e1006206&rft.epage=e1006206&rft.pages=e1006206-e1006206&rft.issn=1553-7374&rft.eissn=1553-7374&rft_id=info:doi/10.1371/journal.ppat.1006206&rft_dat=%3Cgale_plos_%3EA493816471%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1878072493&rft_id=info:pmid/28231264&rft_galeid=A493816471&rft_doaj_id=oai_doaj_org_article_c3ba44008c244969a210e0df7d981249&rfr_iscdi=true |