{"id":{"repo_id":"uiuc","oai_identifier":"oai:www.ideals.illinois.edu:2142/78732"},"canonical_url":"https://search.dev.ndltd.org/etd/uiuc/oai:www.ideals.illinois.edu:2142/78732","repository":{"repo_id":"uiuc","name":"University of Illinois - Urbana-Champaign","base_url":"https://www.ideals.illinois.edu/oai-pmh"},"display":{"title":"Molecular basis of porcine reproductive and respiratory syndrome virus-mediated innate immune suppression","abstract":"Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2017-05-01","abstract_html":"Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2017-05-01","abstract_has_math":false,"creators":["Han, Mingyuan"],"institution":"University of Illinois at Urbana-Champaign","degree_name":"Ph.D.","degree_level":"Dissertation","degree_discipline":"VMS - Pathobiology","degree_department":null,"school":null,"contributors":["Yoo, Dongwan","Gaskins, H. Rex","Rock, Daniel","Zuckermann, Federico","Shisler, Joanna"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2015,"date_issued":"2015-07-22T22:45:15Z","date_published":"2015-07-22T22:45:15Z","updated_at":"2026-07-22T22:26:12Z","subjects":["Arterivirus","Porcine reproductive and respiratory syndrome (PRRSV)","Non-structural protein (nsp)1","Innate immunity","Interferon"],"languages":["en"],"rights":["Copyright 2015 Mingyuan Han"],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/2142/78732","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Yoo, Dongwan","Gaskins, H. Rex","Rock, Daniel","Zuckermann, Federico","Shisler, Joanna"]},{"key":"dc:creator","label":"Author","values":["Han, Mingyuan"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2015-07-22T22:45:15Z","2017-07-23T09:15:24Z","2015-05","2015-04-17","2015-5"]},{"key":"dc:type","label":"Dc Type","values":["text"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["VMS - Pathobiology"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Ph.D."]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["University of Illinois at Urbana-Champaign"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Arterivirus","Porcine reproductive and respiratory syndrome (PRRSV)","Non-structural protein (nsp)1","Innate immunity","Interferon"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en"]},{"key":"dc:rights","label":"Dc Rights","values":["Copyright 2015 Mingyuan Han"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://hdl.handle.net/2142/78732"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2017-05-01","The student, Mingyuan Han, accepted the attached license on 2015-04-16 at 09:06.","The student, Mingyuan Han, submitted this Dissertation for approval on 2015-04-16 at 09:08.","This Dissertation was approved for publication on 2015-04-17 at 09:40.","DSpace SAF Submission Ingestion Package generated from Vireo submission #7850 on 2015-07-22 at 14:24:24","Made available in DSpace on 2015-07-22T22:45:15Z (GMT). No. of bitstreams: 2 HAN-DISSERTATION-2015.pdf: 3792442 bytes, checksum: 73390e0e75671ad926a9576fb0607ee3 (MD5) LICENSE.txt: 4209 bytes, checksum: 4281067cee6c0c081ef5e85ddbd01bf7 (MD5) Previous issue date: 2015-04-17","Embargo set by: Seth Robbins for item 79973 Lift date: 2017-07-22T22:46:21Z Reason: Author requested closed access (OA after 2yrs) in Vireo ETD system","Limited Restriction Lifted for Item 79973 on 2017-07-23T09:15:24Z.","Porcine reproductive and respiratory syndrome (PRRS) is an emerged and re-emerging swine disease featured by severe reproductive losses, post-weaning pneumonia, and increased mortality. During infection of PRRS virus, poor induction of pro-inflammatory cytokines and type I IFNs are observed, and PRRSV seems to have a capacity to escape the immune surveillance for survival. Non-structural protein (nsp) 1 of PRRSV has been identified as a viral IFN antagonist, and nsp1 has been shown to degrade the CREB-binding protein (CBP) and to inhibit the formation of enhanceosome thus resulting in the suppression of IFN production. Nsp1 is auto-processed into nsp1α and nsp1β subunits, and individual subunits (nsp1α and nsp1β) of nsp1 suppress type I IFN production. In the present study, the nsp1α subunit was shown to be responsible for CBP degradation. PRRSV-nsp1β was mainly distributed in the nucleus and played roles for host cell mRNA nuclear retention leading to subversion of host protein synthesis and suppression of type I IFN production. This study was expanded to other member viruses in the family Arteriviridae, and all subunits of arterivirus nsp1 presented the IFN suppressive activity. Similar to PRRSV-nsp1α, CBP degradation was evident in cells expressing LDV-nsp1α and SHFV-nsp1γ. PRRSV-nsp1β-mediated mRNA nuclear accumulation was also observed for LDV-nsp1β and SHFV-nsp1β, but for EAV-nsp1. To study the structure function of PRRSV-nsp1 and its IFN antagonism, motifs for PLP1α (papain-like proteinase 1α), ZF1 (zinc-finger domain 1), and ZF2 within the nsp1α subunit were individually mutated and the mutant proteins were examined for their IFN suppressive ability. Single or double mutations of C8S, C10S, C25S, and/or C28S for the ZF1 motif impaired the IFN antagonism, demonstrating that ZF1 is the essential element of nsp1α for IFN suppression. The ZF1 mutants did not induce CBP degradation and nor IFN suppression. For nsp1β, a SAP motif was identified with the consensus sequence of 126-LQxxLxxxGL-135 by bioinformatics analysis. Cytoplasmic staining was observed for SAP mutants L126, R129A, L130A, and L135A, and these mutants did not cause the nuclear retention of host cell mRNAs, and were unable to inhibit IFN signaling. Using reverse genetics, SAP mutant viable viruses vK124A, vL126A, vG134A, and vL135A were recovered. nsp1β protein was retained in the cytoplasm in cells infected with vL126A and vL135A. Accordingly, no mRNA nuclear retention was observed in these cells, and also no suppression of IFN production was identified. My study demonstrates nsp1 as the type I IFN antagonist in the family Arteriviridae and the molecular basis for this antagonism."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Molecular basis of porcine reproductive and respiratory syndrome virus-mediated innate immune suppression"]}]}],"canonical_facts":{"dc:contributor":["Yoo, Dongwan","Gaskins, H. Rex","Rock, Daniel","Zuckermann, Federico","Shisler, Joanna"],"dc:creator":["Han, Mingyuan"],"dc:date":["2015-07-22T22:45:15Z","2017-07-23T09:15:24Z","2015-05","2015-04-17","2015-5"],"dc:description":["Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2017-05-01","The student, Mingyuan Han, accepted the attached license on 2015-04-16 at 09:06.","The student, Mingyuan Han, submitted this Dissertation for approval on 2015-04-16 at 09:08.","This Dissertation was approved for publication on 2015-04-17 at 09:40.","DSpace SAF Submission Ingestion Package generated from Vireo submission #7850 on 2015-07-22 at 14:24:24","Made available in DSpace on 2015-07-22T22:45:15Z (GMT). No. of bitstreams: 2 HAN-DISSERTATION-2015.pdf: 3792442 bytes, checksum: 73390e0e75671ad926a9576fb0607ee3 (MD5) LICENSE.txt: 4209 bytes, checksum: 4281067cee6c0c081ef5e85ddbd01bf7 (MD5) Previous issue date: 2015-04-17","Embargo set by: Seth Robbins for item 79973 Lift date: 2017-07-22T22:46:21Z Reason: Author requested closed access (OA after 2yrs) in Vireo ETD system","Limited Restriction Lifted for Item 79973 on 2017-07-23T09:15:24Z.","Porcine reproductive and respiratory syndrome (PRRS) is an emerged and re-emerging swine disease featured by severe reproductive losses, post-weaning pneumonia, and increased mortality. During infection of PRRS virus, poor induction of pro-inflammatory cytokines and type I IFNs are observed, and PRRSV seems to have a capacity to escape the immune surveillance for survival. Non-structural protein (nsp) 1 of PRRSV has been identified as a viral IFN antagonist, and nsp1 has been shown to degrade the CREB-binding protein (CBP) and to inhibit the formation of enhanceosome thus resulting in the suppression of IFN production. Nsp1 is auto-processed into nsp1α and nsp1β subunits, and individual subunits (nsp1α and nsp1β) of nsp1 suppress type I IFN production. In the present study, the nsp1α subunit was shown to be responsible for CBP degradation. PRRSV-nsp1β was mainly distributed in the nucleus and played roles for host cell mRNA nuclear retention leading to subversion of host protein synthesis and suppression of type I IFN production. This study was expanded to other member viruses in the family Arteriviridae, and all subunits of arterivirus nsp1 presented the IFN suppressive activity. Similar to PRRSV-nsp1α, CBP degradation was evident in cells expressing LDV-nsp1α and SHFV-nsp1γ. PRRSV-nsp1β-mediated mRNA nuclear accumulation was also observed for LDV-nsp1β and SHFV-nsp1β, but for EAV-nsp1. To study the structure function of PRRSV-nsp1 and its IFN antagonism, motifs for PLP1α (papain-like proteinase 1α), ZF1 (zinc-finger domain 1), and ZF2 within the nsp1α subunit were individually mutated and the mutant proteins were examined for their IFN suppressive ability. Single or double mutations of C8S, C10S, C25S, and/or C28S for the ZF1 motif impaired the IFN antagonism, demonstrating that ZF1 is the essential element of nsp1α for IFN suppression. The ZF1 mutants did not induce CBP degradation and nor IFN suppression. For nsp1β, a SAP motif was identified with the consensus sequence of 126-LQxxLxxxGL-135 by bioinformatics analysis. Cytoplasmic staining was observed for SAP mutants L126, R129A, L130A, and L135A, and these mutants did not cause the nuclear retention of host cell mRNAs, and were unable to inhibit IFN signaling. Using reverse genetics, SAP mutant viable viruses vK124A, vL126A, vG134A, and vL135A were recovered. nsp1β protein was retained in the cytoplasm in cells infected with vL126A and vL135A. Accordingly, no mRNA nuclear retention was observed in these cells, and also no suppression of IFN production was identified. My study demonstrates nsp1 as the type I IFN antagonist in the family Arteriviridae and the molecular basis for this antagonism."],"dc:format":["application/pdf"],"dc:identifier":["http://hdl.handle.net/2142/78732"],"dc:language":["en"],"dc:rights":["Copyright 2015 Mingyuan Han"],"dc:subject":["Arterivirus","Porcine reproductive and respiratory syndrome (PRRSV)","Non-structural protein (nsp)1","Innate immunity","Interferon"],"dc:title":["Molecular basis of porcine reproductive and respiratory syndrome virus-mediated innate immune suppression"],"dc:type":["text"],"thesis:degree_discipline":["VMS - Pathobiology"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Ph.D."],"thesis:institution_name":["University of Illinois at Urbana-Champaign"]},"updated_at":"2026-07-22T22:26:12Z"}