RNA-Seq analysis of chikungunya virus infection and identification of granzyme A as a major promoter of arthritic inflammation
Identifieur interne : 000508 ( Main/Exploration ); précédent : 000507; suivant : 000509RNA-Seq analysis of chikungunya virus infection and identification of granzyme A as a major promoter of arthritic inflammation
Auteurs : Jane A. C. Wilson [Australie] ; Natalie A. Prow [Australie] ; Wayne A. Schroder [Australie] ; Jonathan J. Ellis [Australie] ; Helen E. Cumming [Australie] ; Linden J. Gearing [Australie] ; Yee Suan Poo [Australie] ; Adam Taylor [Australie] ; Paul J. Hertzog [Australie] ; Francesca Di Giallonardo [Australie] ; Linda Hueston [Australie] ; Roger Le Grand [France] ; Bing Tang [Australie] ; Thuy T. Le [Australie] ; Joy Gardner [Australie] ; Suresh Mahalingam [Australie] ; Pierre Roques [France] ; Phillip I. Bird [Australie] ; Andreas Suhrbier [Australie]Source :
- PLoS Pathogens [ 1553-7366 ] ; 2017.
Descripteurs français
- KwdFr :
- ARN messager (analyse), Animaux, Arthrite (virologie), Fièvre chikungunya (génétique), Fièvre chikungunya (immunologie), Granzymes (analyse), Granzymes (biosynthèse), Granzymes (immunologie), Humains, Immunohistochimie, Inflammation (virologie), Macaca fascicularis, Modèles animaux de maladie humaine, Souris, Souris de lignée C57BL, Souris knockout, Transcriptome, Virus du chikungunya.
- MESH :
- analyse : ARN messager, Granzymes.
- biosynthèse : Granzymes.
- génétique : Fièvre chikungunya.
- immunologie : Fièvre chikungunya, Granzymes.
- virologie : Arthrite, Inflammation.
- Animaux, Humains, Immunohistochimie, Macaca fascicularis, Modèles animaux de maladie humaine, Souris, Souris de lignée C57BL, Souris knockout, Transcriptome, Virus du chikungunya.
English descriptors
- KwdEn :
- Animals, Arthritis (virology), Chikungunya Fever (genetics), Chikungunya Fever (immunology), Chikungunya virus, Disease Models, Animal, Granzymes (analysis), Granzymes (biosynthesis), Granzymes (immunology), Humans, Immunohistochemistry, Inflammation (virology), Macaca fascicularis, Mice, Mice, Inbred C57BL, Mice, Knockout, RNA, Messenger (analysis), Transcriptome.
- MESH :
- chemical , analysis : Granzymes, RNA, Messenger.
- chemical , biosynthesis : Granzymes.
- genetics : Chikungunya Fever.
- immunology : Chikungunya Fever, Granzymes.
- virology : Arthritis, Inflammation.
- Animals, Chikungunya virus, Disease Models, Animal, Humans, Immunohistochemistry, Macaca fascicularis, Mice, Mice, Inbred C57BL, Mice, Knockout, Transcriptome.
Abstract
Chikungunya virus (CHIKV) is an arthritogenic alphavirus causing epidemics of acute and chronic arthritic disease. Herein we describe a comprehensive RNA-Seq analysis of feet and lymph nodes at peak viraemia (day 2 post infection), acute arthritis (day 7) and chronic disease (day 30) in the CHIKV adult wild-type mouse model. Genes previously shown to be up-regulated in CHIKV patients were also up-regulated in the mouse model. CHIKV sequence information was also obtained with up to ≈8% of the reads mapping to the viral genome; however, no adaptive viral genome changes were apparent. Although day 2, 7 and 30 represent distinct stages of infection and disease, there was a pronounced overlap in up-regulated host genes and pathways. Type I interferon response genes (IRGs) represented up to ≈50% of up-regulated genes, even after loss of type I interferon induction on days 7 and 30. Bioinformatic analyses suggested a number of interferon response factors were primarily responsible for maintaining type I IRG induction. A group of genes prominent in the RNA-Seq analysis and hitherto unexplored in viral arthropathies were granzymes A, B and K. Granzyme A-/- and to a lesser extent granzyme K-/-, but not granzyme B-/-, mice showed a pronounced reduction in foot swelling and arthritis, with analysis of granzyme A-/- mice showing no reductions in viral loads but reduced NK and T cell infiltrates post CHIKV infection. Treatment with Serpinb6b, a granzyme A inhibitor, also reduced arthritic inflammation in wild-type mice. In non-human primates circulating granzyme A levels were elevated after CHIKV infection, with the increase correlating with viral load. Elevated granzyme A levels were also seen in a small cohort of human CHIKV patients. Taken together these results suggest granzyme A is an important driver of arthritic inflammation and a potential target for therapy.
Url:
DOI: 10.1371/journal.ppat.1006155
PubMed: 28207896
PubMed Central: 5312928
Affiliations:
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Le document en format XML
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</author>
<author><name sortKey="Di Giallonardo, Francesca" sort="Di Giallonardo, Francesca" uniqKey="Di Giallonardo F" first="Francesca" last="Di Giallonardo">Francesca Di Giallonardo</name>
<affiliation wicri:level="4"><nlm:aff id="aff005"><addr-line>Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia</addr-line>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Charles Perkins Centre, The University of Sydney, Sydney, NSW</wicri:regionArea>
<orgName type="university">Université de Sydney</orgName>
<placeName><settlement type="city">Sydney</settlement>
<region type="état">Nouvelle-Galles du Sud</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Hueston, Linda" sort="Hueston, Linda" uniqKey="Hueston L" first="Linda" last="Hueston">Linda Hueston</name>
<affiliation wicri:level="1"><nlm:aff id="aff006"><addr-line>Centre for Infectious Diseases and Microbiology Laboratory Services, Westmead Hospital, Sydney, NSW, Australia</addr-line>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Centre for Infectious Diseases and Microbiology Laboratory Services, Westmead Hospital, Sydney, NSW</wicri:regionArea>
<wicri:noRegion>NSW</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Le Grand, Roger" sort="Le Grand, Roger" uniqKey="Le Grand R" first="Roger" last="Le Grand">Roger Le Grand</name>
<affiliation wicri:level="1"><nlm:aff id="aff007"><addr-line>CEA, Inserm, Université Paris Sud; iMETI; UMR 1184 Immunology of Viral infections and Autoimmune diseases, Fontenay-aux-Roses, France</addr-line>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>CEA, Inserm, Université Paris Sud; iMETI; UMR 1184 Immunology of Viral infections and Autoimmune diseases, Fontenay-aux-Roses</wicri:regionArea>
<wicri:noRegion>Fontenay-aux-Roses</wicri:noRegion>
<wicri:noRegion>Fontenay-aux-Roses</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Tang, Bing" sort="Tang, Bing" uniqKey="Tang B" first="Bing" last="Tang">Bing Tang</name>
<affiliation wicri:level="1"><nlm:aff id="aff001"><addr-line>QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia</addr-line>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>QIMR Berghofer Medical Research Institute, Brisbane, Queensland</wicri:regionArea>
<wicri:noRegion>Queensland</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Le, Thuy T" sort="Le, Thuy T" uniqKey="Le T" first="Thuy T." last="Le">Thuy T. Le</name>
<affiliation wicri:level="1"><nlm:aff id="aff001"><addr-line>QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia</addr-line>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>QIMR Berghofer Medical Research Institute, Brisbane, Queensland</wicri:regionArea>
<wicri:noRegion>Queensland</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Gardner, Joy" sort="Gardner, Joy" uniqKey="Gardner J" first="Joy" last="Gardner">Joy Gardner</name>
<affiliation wicri:level="1"><nlm:aff id="aff001"><addr-line>QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia</addr-line>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>QIMR Berghofer Medical Research Institute, Brisbane, Queensland</wicri:regionArea>
<wicri:noRegion>Queensland</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Mahalingam, Suresh" sort="Mahalingam, Suresh" uniqKey="Mahalingam S" first="Suresh" last="Mahalingam">Suresh Mahalingam</name>
<affiliation wicri:level="1"><nlm:aff id="aff004"><addr-line>Institute for Glycomics, Griffith University, Gold Coast, Queensland, Australia</addr-line>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Institute for Glycomics, Griffith University, Gold Coast, Queensland</wicri:regionArea>
<wicri:noRegion>Queensland</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Roques, Pierre" sort="Roques, Pierre" uniqKey="Roques P" first="Pierre" last="Roques">Pierre Roques</name>
<affiliation wicri:level="1"><nlm:aff id="aff007"><addr-line>CEA, Inserm, Université Paris Sud; iMETI; UMR 1184 Immunology of Viral infections and Autoimmune diseases, Fontenay-aux-Roses, France</addr-line>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>CEA, Inserm, Université Paris Sud; iMETI; UMR 1184 Immunology of Viral infections and Autoimmune diseases, Fontenay-aux-Roses</wicri:regionArea>
<wicri:noRegion>Fontenay-aux-Roses</wicri:noRegion>
<wicri:noRegion>Fontenay-aux-Roses</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Bird, Phillip I" sort="Bird, Phillip I" uniqKey="Bird P" first="Phillip I." last="Bird">Phillip I. Bird</name>
<affiliation wicri:level="1"><nlm:aff id="aff008"><addr-line>Biomedicine Discovery Institute, Monash University, Victoria 3800, Australia</addr-line>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Biomedicine Discovery Institute, Monash University, Victoria 3800</wicri:regionArea>
<wicri:noRegion>Victoria 3800</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Suhrbier, Andreas" sort="Suhrbier, Andreas" uniqKey="Suhrbier A" first="Andreas" last="Suhrbier">Andreas Suhrbier</name>
<affiliation wicri:level="1"><nlm:aff id="aff001"><addr-line>QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia</addr-line>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>QIMR Berghofer Medical Research Institute, Brisbane, Queensland</wicri:regionArea>
<wicri:noRegion>Queensland</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff002"><addr-line>Australian Infectious Disease Research Centre, The University of Queensland, Brisbane, Queensland, Australia</addr-line>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Australian Infectious Disease Research Centre, The University of Queensland, Brisbane, Queensland</wicri:regionArea>
<wicri:noRegion>Queensland</wicri:noRegion>
</affiliation>
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</analytic>
<series><title level="j">PLoS Pathogens</title>
<idno type="ISSN">1553-7366</idno>
<idno type="eISSN">1553-7374</idno>
<imprint><date when="2017">2017</date>
</imprint>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term>
<term>Arthritis (virology)</term>
<term>Chikungunya Fever (genetics)</term>
<term>Chikungunya Fever (immunology)</term>
<term>Chikungunya virus</term>
<term>Disease Models, Animal</term>
<term>Granzymes (analysis)</term>
<term>Granzymes (biosynthesis)</term>
<term>Granzymes (immunology)</term>
<term>Humans</term>
<term>Immunohistochemistry</term>
<term>Inflammation (virology)</term>
<term>Macaca fascicularis</term>
<term>Mice</term>
<term>Mice, Inbred C57BL</term>
<term>Mice, Knockout</term>
<term>RNA, Messenger (analysis)</term>
<term>Transcriptome</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>ARN messager (analyse)</term>
<term>Animaux</term>
<term>Arthrite (virologie)</term>
<term>Fièvre chikungunya (génétique)</term>
<term>Fièvre chikungunya (immunologie)</term>
<term>Granzymes (analyse)</term>
<term>Granzymes (biosynthèse)</term>
<term>Granzymes (immunologie)</term>
<term>Humains</term>
<term>Immunohistochimie</term>
<term>Inflammation (virologie)</term>
<term>Macaca fascicularis</term>
<term>Modèles animaux de maladie humaine</term>
<term>Souris</term>
<term>Souris de lignée C57BL</term>
<term>Souris knockout</term>
<term>Transcriptome</term>
<term>Virus du chikungunya</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="analysis" xml:lang="en"><term>Granzymes</term>
<term>RNA, Messenger</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="biosynthesis" xml:lang="en"><term>Granzymes</term>
</keywords>
<keywords scheme="MESH" qualifier="analyse" xml:lang="fr"><term>ARN messager</term>
<term>Granzymes</term>
</keywords>
<keywords scheme="MESH" qualifier="biosynthèse" xml:lang="fr"><term>Granzymes</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Chikungunya Fever</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Fièvre chikungunya</term>
</keywords>
<keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Fièvre chikungunya</term>
<term>Granzymes</term>
</keywords>
<keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Chikungunya Fever</term>
<term>Granzymes</term>
</keywords>
<keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Arthrite</term>
<term>Inflammation</term>
</keywords>
<keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Arthritis</term>
<term>Inflammation</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Animals</term>
<term>Chikungunya virus</term>
<term>Disease Models, Animal</term>
<term>Humans</term>
<term>Immunohistochemistry</term>
<term>Macaca fascicularis</term>
<term>Mice</term>
<term>Mice, Inbred C57BL</term>
<term>Mice, Knockout</term>
<term>Transcriptome</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Animaux</term>
<term>Humains</term>
<term>Immunohistochimie</term>
<term>Macaca fascicularis</term>
<term>Modèles animaux de maladie humaine</term>
<term>Souris</term>
<term>Souris de lignée C57BL</term>
<term>Souris knockout</term>
<term>Transcriptome</term>
<term>Virus du chikungunya</term>
</keywords>
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<front><div type="abstract" xml:lang="en"><p>Chikungunya virus (CHIKV) is an arthritogenic alphavirus causing epidemics of acute and chronic arthritic disease. Herein we describe a comprehensive RNA-Seq analysis of feet and lymph nodes at peak viraemia (day 2 post infection), acute arthritis (day 7) and chronic disease (day 30) in the CHIKV adult wild-type mouse model. Genes previously shown to be up-regulated in CHIKV patients were also up-regulated in the mouse model. CHIKV sequence information was also obtained with up to ≈8% of the reads mapping to the viral genome; however, no adaptive viral genome changes were apparent. Although day 2, 7 and 30 represent distinct stages of infection and disease, there was a pronounced overlap in up-regulated host genes and pathways. Type I interferon response genes (IRGs) represented up to ≈50% of up-regulated genes, even after loss of type I interferon induction on days 7 and 30. Bioinformatic analyses suggested a number of interferon response factors were primarily responsible for maintaining type I IRG induction. A group of genes prominent in the RNA-Seq analysis and hitherto unexplored in viral arthropathies were granzymes A, B and K. Granzyme A<sup>-/-</sup>
and to a lesser extent granzyme K<sup>-/-</sup>
, but not granzyme B<sup>-/-</sup>
, mice showed a pronounced reduction in foot swelling and arthritis, with analysis of granzyme A<sup>-/-</sup>
mice showing no reductions in viral loads but reduced NK and T cell infiltrates post CHIKV infection. Treatment with Serpinb6b, a granzyme A inhibitor, also reduced arthritic inflammation in wild-type mice. In non-human primates circulating granzyme A levels were elevated after CHIKV infection, with the increase correlating with viral load. Elevated granzyme A levels were also seen in a small cohort of human CHIKV patients. Taken together these results suggest granzyme A is an important driver of arthritic inflammation and a potential target for therapy.</p>
<p><bold>Trial Registration:</bold>
ClinicalTrials.gov <ext-link ext-link-type="uri" xlink:href="https://clinicaltrials.gov/ct2/show/NCT00281294">NCT00281294</ext-link>
</p>
</div>
</front>
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<biblStruct><analytic><author><name sortKey="Trapnell, C" uniqKey="Trapnell C">C Trapnell</name>
</author>
<author><name sortKey="Roberts, A" uniqKey="Roberts A">A Roberts</name>
</author>
<author><name sortKey="Goff, L" uniqKey="Goff L">L Goff</name>
</author>
<author><name sortKey="Pertea, G" uniqKey="Pertea G">G Pertea</name>
</author>
<author><name sortKey="Kim, D" uniqKey="Kim D">D Kim</name>
</author>
<author><name sortKey="Kelley, Dr" uniqKey="Kelley D">DR Kelley</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Trapnell, C" uniqKey="Trapnell C">C Trapnell</name>
</author>
<author><name sortKey="Williams, Ba" uniqKey="Williams B">BA Williams</name>
</author>
<author><name sortKey="Pertea, G" uniqKey="Pertea G">G Pertea</name>
</author>
<author><name sortKey="Mortazavi, A" uniqKey="Mortazavi A">A Mortazavi</name>
</author>
<author><name sortKey="Kwan, G" uniqKey="Kwan G">G Kwan</name>
</author>
<author><name sortKey="Van Baren, Mj" uniqKey="Van Baren M">MJ van Baren</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Huang Da, W" uniqKey="Huang Da W">W Huang da</name>
</author>
<author><name sortKey="Sherman, Bt" uniqKey="Sherman B">BT Sherman</name>
</author>
<author><name sortKey="Lempicki, Ra" uniqKey="Lempicki R">RA Lempicki</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Thorvaldsdottir, H" uniqKey="Thorvaldsdottir H">H Thorvaldsdottir</name>
</author>
<author><name sortKey="Robinson, Jt" uniqKey="Robinson J">JT Robinson</name>
</author>
<author><name sortKey="Mesirov, Jp" uniqKey="Mesirov J">JP Mesirov</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Kearse, M" uniqKey="Kearse M">M Kearse</name>
</author>
<author><name sortKey="Moir, R" uniqKey="Moir R">R Moir</name>
</author>
<author><name sortKey="Wilson, A" uniqKey="Wilson A">A Wilson</name>
</author>
<author><name sortKey="Stones Havas, S" uniqKey="Stones Havas S">S Stones-Havas</name>
</author>
<author><name sortKey="Cheung, M" uniqKey="Cheung M">M Cheung</name>
</author>
<author><name sortKey="Sturrock, S" uniqKey="Sturrock S">S Sturrock</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Kel, Ae" uniqKey="Kel A">AE Kel</name>
</author>
<author><name sortKey="Gossling, E" uniqKey="Gossling E">E Gossling</name>
</author>
<author><name sortKey="Reuter, I" uniqKey="Reuter I">I Reuter</name>
</author>
<author><name sortKey="Cheremushkin, E" uniqKey="Cheremushkin E">E Cheremushkin</name>
</author>
<author><name sortKey="Kel Margoulis, Ov" uniqKey="Kel Margoulis O">OV Kel-Margoulis</name>
</author>
<author><name sortKey="Wingender, E" uniqKey="Wingender E">E Wingender</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Frith, Mc" uniqKey="Frith M">MC Frith</name>
</author>
<author><name sortKey="Fu, Y" uniqKey="Fu Y">Y Fu</name>
</author>
<author><name sortKey="Yu, L" uniqKey="Yu L">L Yu</name>
</author>
<author><name sortKey="Chen, Jf" uniqKey="Chen J">JF Chen</name>
</author>
<author><name sortKey="Hansen, U" uniqKey="Hansen U">U Hansen</name>
</author>
<author><name sortKey="Weng, Z" uniqKey="Weng Z">Z Weng</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Sun, J" uniqKey="Sun J">J Sun</name>
</author>
<author><name sortKey="Coughlin, P" uniqKey="Coughlin P">P Coughlin</name>
</author>
<author><name sortKey="Salem, Hh" uniqKey="Salem H">HH Salem</name>
</author>
<author><name sortKey="Bird, P" uniqKey="Bird P">P Bird</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Risso, D" uniqKey="Risso D">D Risso</name>
</author>
<author><name sortKey="Schwartz, K" uniqKey="Schwartz K">K Schwartz</name>
</author>
<author><name sortKey="Sherlock, G" uniqKey="Sherlock G">G Sherlock</name>
</author>
<author><name sortKey="Dudoit, S" uniqKey="Dudoit S">S Dudoit</name>
</author>
</analytic>
</biblStruct>
</listBibl>
</div1>
</back>
</TEI>
<affiliations><list><country><li>Australie</li>
<li>France</li>
</country>
<region><li>Nouvelle-Galles du Sud</li>
</region>
<settlement><li>Sydney</li>
</settlement>
<orgName><li>Université de Sydney</li>
</orgName>
</list>
<tree><country name="Australie"><noRegion><name sortKey="Wilson, Jane A C" sort="Wilson, Jane A C" uniqKey="Wilson J" first="Jane A. C." last="Wilson">Jane A. C. Wilson</name>
</noRegion>
<name sortKey="Bird, Phillip I" sort="Bird, Phillip I" uniqKey="Bird P" first="Phillip I." last="Bird">Phillip I. Bird</name>
<name sortKey="Cumming, Helen E" sort="Cumming, Helen E" uniqKey="Cumming H" first="Helen E." last="Cumming">Helen E. Cumming</name>
<name sortKey="Di Giallonardo, Francesca" sort="Di Giallonardo, Francesca" uniqKey="Di Giallonardo F" first="Francesca" last="Di Giallonardo">Francesca Di Giallonardo</name>
<name sortKey="Ellis, Jonathan J" sort="Ellis, Jonathan J" uniqKey="Ellis J" first="Jonathan J." last="Ellis">Jonathan J. Ellis</name>
<name sortKey="Gardner, Joy" sort="Gardner, Joy" uniqKey="Gardner J" first="Joy" last="Gardner">Joy Gardner</name>
<name sortKey="Gearing, Linden J" sort="Gearing, Linden J" uniqKey="Gearing L" first="Linden J." last="Gearing">Linden J. Gearing</name>
<name sortKey="Hertzog, Paul J" sort="Hertzog, Paul J" uniqKey="Hertzog P" first="Paul J." last="Hertzog">Paul J. Hertzog</name>
<name sortKey="Hueston, Linda" sort="Hueston, Linda" uniqKey="Hueston L" first="Linda" last="Hueston">Linda Hueston</name>
<name sortKey="Le, Thuy T" sort="Le, Thuy T" uniqKey="Le T" first="Thuy T." last="Le">Thuy T. Le</name>
<name sortKey="Mahalingam, Suresh" sort="Mahalingam, Suresh" uniqKey="Mahalingam S" first="Suresh" last="Mahalingam">Suresh Mahalingam</name>
<name sortKey="Poo, Yee Suan" sort="Poo, Yee Suan" uniqKey="Poo Y" first="Yee Suan" last="Poo">Yee Suan Poo</name>
<name sortKey="Poo, Yee Suan" sort="Poo, Yee Suan" uniqKey="Poo Y" first="Yee Suan" last="Poo">Yee Suan Poo</name>
<name sortKey="Prow, Natalie A" sort="Prow, Natalie A" uniqKey="Prow N" first="Natalie A." last="Prow">Natalie A. Prow</name>
<name sortKey="Schroder, Wayne A" sort="Schroder, Wayne A" uniqKey="Schroder W" first="Wayne A." last="Schroder">Wayne A. Schroder</name>
<name sortKey="Suhrbier, Andreas" sort="Suhrbier, Andreas" uniqKey="Suhrbier A" first="Andreas" last="Suhrbier">Andreas Suhrbier</name>
<name sortKey="Suhrbier, Andreas" sort="Suhrbier, Andreas" uniqKey="Suhrbier A" first="Andreas" last="Suhrbier">Andreas Suhrbier</name>
<name sortKey="Tang, Bing" sort="Tang, Bing" uniqKey="Tang B" first="Bing" last="Tang">Bing Tang</name>
<name sortKey="Taylor, Adam" sort="Taylor, Adam" uniqKey="Taylor A" first="Adam" last="Taylor">Adam Taylor</name>
<name sortKey="Wilson, Jane A C" sort="Wilson, Jane A C" uniqKey="Wilson J" first="Jane A. C." last="Wilson">Jane A. C. Wilson</name>
</country>
<country name="France"><noRegion><name sortKey="Le Grand, Roger" sort="Le Grand, Roger" uniqKey="Le Grand R" first="Roger" last="Le Grand">Roger Le Grand</name>
</noRegion>
<name sortKey="Roques, Pierre" sort="Roques, Pierre" uniqKey="Roques P" first="Pierre" last="Roques">Pierre Roques</name>
</country>
</tree>
</affiliations>
</record>
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