RNA-Seq analysis of chikungunya virus infection and identification of granzyme A as a major promoter of arthritic inflammation.
Identifieur interne : 001138 ( PubMed/Corpus ); précédent : 001137; suivant : 001139RNA-Seq analysis of chikungunya virus infection and identification of granzyme A as a major promoter of arthritic inflammation.
Auteurs : Jane A C. Wilson ; Natalie A. Prow ; Wayne A. Schroder ; Jonathan J. Ellis ; Helen E. Cumming ; Linden J. Gearing ; Yee Suan Poo ; Adam Taylor ; Paul J. Hertzog ; Francesca Di Giallonardo ; Linda Hueston ; Roger Le Grand ; Bing Tang ; Thuy T. Le ; Joy Gardner ; Suresh Mahalingam ; Pierre Roques ; Phillip I. Bird ; Andreas SuhrbierSource :
- PLoS pathogens [ 1553-7374 ] ; 2017.
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.
DOI: 10.1371/journal.ppat.1006155
PubMed: 28207896
Links to Exploration step
pubmed:28207896Le document en format XML
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Schroder</name><affiliation><nlm:affiliation>QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Ellis, Jonathan J" sort="Ellis, Jonathan J" uniqKey="Ellis J" first="Jonathan J" last="Ellis">Jonathan J. Ellis</name><affiliation><nlm:affiliation>QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Cumming, Helen E" sort="Cumming, Helen E" uniqKey="Cumming H" first="Helen E" last="Cumming">Helen E. Cumming</name><affiliation><nlm:affiliation>Hudson Institute of Medical Research, Clayton, Victoria, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Gearing, Linden J" sort="Gearing, Linden J" uniqKey="Gearing L" first="Linden J" last="Gearing">Linden J. Gearing</name><affiliation><nlm:affiliation>Hudson Institute of Medical Research, Clayton, Victoria, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Poo, Yee Suan" sort="Poo, Yee Suan" uniqKey="Poo Y" first="Yee Suan" last="Poo">Yee Suan Poo</name><affiliation><nlm:affiliation>QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Taylor, Adam" sort="Taylor, Adam" uniqKey="Taylor A" first="Adam" last="Taylor">Adam Taylor</name><affiliation><nlm:affiliation>Institute for Glycomics, Griffith University, Gold Coast, Queensland, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Hertzog, Paul J" sort="Hertzog, Paul J" uniqKey="Hertzog P" first="Paul J" last="Hertzog">Paul J. Hertzog</name><affiliation><nlm:affiliation>Hudson Institute of Medical Research, Clayton, Victoria, Australia.</nlm:affiliation></affiliation></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><nlm:affiliation>Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Hueston, Linda" sort="Hueston, Linda" uniqKey="Hueston L" first="Linda" last="Hueston">Linda Hueston</name><affiliation><nlm:affiliation>Centre for Infectious Diseases and Microbiology Laboratory Services, Westmead Hospital, Sydney, NSW, Australia.</nlm:affiliation></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><nlm:affiliation>CEA, Inserm, Université Paris Sud; iMETI; UMR 1184 Immunology of Viral infections and Autoimmune diseases, Fontenay-aux-Roses, France.</nlm:affiliation></affiliation></author><author><name sortKey="Tang, Bing" sort="Tang, Bing" uniqKey="Tang B" first="Bing" last="Tang">Bing Tang</name><affiliation><nlm:affiliation>QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.</nlm:affiliation></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><nlm:affiliation>QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Gardner, Joy" sort="Gardner, Joy" uniqKey="Gardner J" first="Joy" last="Gardner">Joy Gardner</name><affiliation><nlm:affiliation>QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Mahalingam, Suresh" sort="Mahalingam, Suresh" uniqKey="Mahalingam S" first="Suresh" last="Mahalingam">Suresh Mahalingam</name><affiliation><nlm:affiliation>Institute for Glycomics, Griffith University, Gold Coast, Queensland, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Roques, Pierre" sort="Roques, Pierre" uniqKey="Roques P" first="Pierre" last="Roques">Pierre Roques</name><affiliation><nlm:affiliation>CEA, Inserm, Université Paris Sud; iMETI; UMR 1184 Immunology of Viral infections and Autoimmune diseases, Fontenay-aux-Roses, France.</nlm:affiliation></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><nlm:affiliation>Biomedicine Discovery Institute, Monash University, Victoria 3800, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Suhrbier, Andreas" sort="Suhrbier, Andreas" uniqKey="Suhrbier A" first="Andreas" last="Suhrbier">Andreas Suhrbier</name><affiliation><nlm:affiliation>QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.</nlm:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2017">2017</date><idno type="RBID">pubmed:28207896</idno><idno type="pmid">28207896</idno><idno type="doi">10.1371/journal.ppat.1006155</idno><idno type="wicri:Area/PubMed/Corpus">001138</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">001138</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">RNA-Seq analysis of chikungunya virus infection and identification of granzyme A as a major promoter of arthritic inflammation.</title><author><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><affiliation><nlm:affiliation>QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Prow, Natalie A" sort="Prow, Natalie A" uniqKey="Prow N" first="Natalie A" last="Prow">Natalie A. Prow</name><affiliation><nlm:affiliation>QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Schroder, Wayne A" sort="Schroder, Wayne A" uniqKey="Schroder W" first="Wayne A" last="Schroder">Wayne A. Schroder</name><affiliation><nlm:affiliation>QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Ellis, Jonathan J" sort="Ellis, Jonathan J" uniqKey="Ellis J" first="Jonathan J" last="Ellis">Jonathan J. Ellis</name><affiliation><nlm:affiliation>QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Cumming, Helen E" sort="Cumming, Helen E" uniqKey="Cumming H" first="Helen E" last="Cumming">Helen E. Cumming</name><affiliation><nlm:affiliation>Hudson Institute of Medical Research, Clayton, Victoria, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Gearing, Linden J" sort="Gearing, Linden J" uniqKey="Gearing L" first="Linden J" last="Gearing">Linden J. Gearing</name><affiliation><nlm:affiliation>Hudson Institute of Medical Research, Clayton, Victoria, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Poo, Yee Suan" sort="Poo, Yee Suan" uniqKey="Poo Y" first="Yee Suan" last="Poo">Yee Suan Poo</name><affiliation><nlm:affiliation>QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Taylor, Adam" sort="Taylor, Adam" uniqKey="Taylor A" first="Adam" last="Taylor">Adam Taylor</name><affiliation><nlm:affiliation>Institute for Glycomics, Griffith University, Gold Coast, Queensland, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Hertzog, Paul J" sort="Hertzog, Paul J" uniqKey="Hertzog P" first="Paul J" last="Hertzog">Paul J. Hertzog</name><affiliation><nlm:affiliation>Hudson Institute of Medical Research, Clayton, Victoria, Australia.</nlm:affiliation></affiliation></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><nlm:affiliation>Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Hueston, Linda" sort="Hueston, Linda" uniqKey="Hueston L" first="Linda" last="Hueston">Linda Hueston</name><affiliation><nlm:affiliation>Centre for Infectious Diseases and Microbiology Laboratory Services, Westmead Hospital, Sydney, NSW, Australia.</nlm:affiliation></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><nlm:affiliation>CEA, Inserm, Université Paris Sud; iMETI; UMR 1184 Immunology of Viral infections and Autoimmune diseases, Fontenay-aux-Roses, France.</nlm:affiliation></affiliation></author><author><name sortKey="Tang, Bing" sort="Tang, Bing" uniqKey="Tang B" first="Bing" last="Tang">Bing Tang</name><affiliation><nlm:affiliation>QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.</nlm:affiliation></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><nlm:affiliation>QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Gardner, Joy" sort="Gardner, Joy" uniqKey="Gardner J" first="Joy" last="Gardner">Joy Gardner</name><affiliation><nlm:affiliation>QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Mahalingam, Suresh" sort="Mahalingam, Suresh" uniqKey="Mahalingam S" first="Suresh" last="Mahalingam">Suresh Mahalingam</name><affiliation><nlm:affiliation>Institute for Glycomics, Griffith University, Gold Coast, Queensland, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Roques, Pierre" sort="Roques, Pierre" uniqKey="Roques P" first="Pierre" last="Roques">Pierre Roques</name><affiliation><nlm:affiliation>CEA, Inserm, Université Paris Sud; iMETI; UMR 1184 Immunology of Viral infections and Autoimmune diseases, Fontenay-aux-Roses, France.</nlm:affiliation></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><nlm:affiliation>Biomedicine Discovery Institute, Monash University, Victoria 3800, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Suhrbier, Andreas" sort="Suhrbier, Andreas" uniqKey="Suhrbier A" first="Andreas" last="Suhrbier">Andreas Suhrbier</name><affiliation><nlm:affiliation>QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.</nlm:affiliation></affiliation></author></analytic><series><title level="j">PLoS pathogens</title><idno type="eISSN">1553-7374</idno><imprint><date when="2017" type="published">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><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="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="genetics" xml:lang="en"><term>Chikungunya Fever</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Chikungunya Fever</term><term>Granzymes</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></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">28207896</PMID><DateCreated><Year>2017</Year><Month>02</Month><Day>16</Day></DateCreated><DateCompleted><Year>2017</Year><Month>08</Month><Day>03</Day></DateCompleted><DateRevised><Year>2017</Year><Month>08</Month><Day>03</Day></DateRevised><Article PubModel="Electronic-eCollection"><Journal><ISSN IssnType="Electronic">1553-7374</ISSN><JournalIssue CitedMedium="Internet"><Volume>13</Volume><Issue>2</Issue><PubDate><Year>2017</Year><Month>Feb</Month></PubDate></JournalIssue><Title>PLoS pathogens</Title><ISOAbbreviation>PLoS Pathog.</ISOAbbreviation></Journal><ArticleTitle>RNA-Seq analysis of chikungunya virus infection and identification of granzyme A as a major promoter of arthritic inflammation.</ArticleTitle><Pagination><MedlinePgn>e1006155</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1371/journal.ppat.1006155</ELocationID><Abstract><AbstractText>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.</AbstractText><AbstractText Label="TRIAL REGISTRATION" NlmCategory="BACKGROUND">ClinicalTrials.gov NCT00281294.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Wilson</LastName><ForeName>Jane A C</ForeName><Initials>JA</Initials><AffiliationInfo><Affiliation>QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Australian Infectious Disease Research Centre, The University of Queensland, Brisbane, Queensland, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Prow</LastName><ForeName>Natalie A</ForeName><Initials>NA</Initials><AffiliationInfo><Affiliation>QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Schroder</LastName><ForeName>Wayne A</ForeName><Initials>WA</Initials><AffiliationInfo><Affiliation>QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ellis</LastName><ForeName>Jonathan J</ForeName><Initials>JJ</Initials><AffiliationInfo><Affiliation>QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cumming</LastName><ForeName>Helen E</ForeName><Initials>HE</Initials><AffiliationInfo><Affiliation>Hudson Institute of Medical Research, Clayton, Victoria, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gearing</LastName><ForeName>Linden J</ForeName><Initials>LJ</Initials><Identifier Source="ORCID">http://orcid.org/0000-0003-3508-3056</Identifier><AffiliationInfo><Affiliation>Hudson Institute of Medical Research, Clayton, Victoria, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Poo</LastName><ForeName>Yee Suan</ForeName><Initials>YS</Initials><AffiliationInfo><Affiliation>QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Australian Infectious Disease Research Centre, The University of Queensland, Brisbane, Queensland, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Taylor</LastName><ForeName>Adam</ForeName><Initials>A</Initials><Identifier Source="ORCID">http://orcid.org/0000-0002-7159-3961</Identifier><AffiliationInfo><Affiliation>Institute for Glycomics, Griffith University, Gold Coast, Queensland, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hertzog</LastName><ForeName>Paul J</ForeName><Initials>PJ</Initials><AffiliationInfo><Affiliation>Hudson Institute of Medical Research, Clayton, Victoria, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Di Giallonardo</LastName><ForeName>Francesca</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hueston</LastName><ForeName>Linda</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Centre for Infectious Diseases and Microbiology Laboratory Services, Westmead Hospital, Sydney, NSW, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Le Grand</LastName><ForeName>Roger</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>CEA, Inserm, Université Paris Sud; iMETI; UMR 1184 Immunology of Viral infections and Autoimmune diseases, Fontenay-aux-Roses, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Tang</LastName><ForeName>Bing</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Le</LastName><ForeName>Thuy T</ForeName><Initials>TT</Initials><Identifier Source="ORCID">http://orcid.org/0000-0001-9134-0104</Identifier><AffiliationInfo><Affiliation>QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gardner</LastName><ForeName>Joy</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Mahalingam</LastName><ForeName>Suresh</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Institute for Glycomics, Griffith University, Gold Coast, Queensland, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Roques</LastName><ForeName>Pierre</ForeName><Initials>P</Initials><Identifier Source="ORCID">http://orcid.org/0000-0003-1825-1054</Identifier><AffiliationInfo><Affiliation>CEA, Inserm, Université Paris Sud; iMETI; UMR 1184 Immunology of Viral infections and Autoimmune diseases, Fontenay-aux-Roses, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bird</LastName><ForeName>Phillip I</ForeName><Initials>PI</Initials><AffiliationInfo><Affiliation>Biomedicine Discovery Institute, Monash University, Victoria 3800, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Suhrbier</LastName><ForeName>Andreas</ForeName><Initials>A</Initials><Identifier Source="ORCID">http://orcid.org/0000-0001-8986-9025</Identifier><AffiliationInfo><Affiliation>QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Australian Infectious Disease Research Centre, The University of Queensland, Brisbane, Queensland, Australia.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2017</Year><Month>02</Month><Day>16</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>PLoS Pathog</MedlineTA><NlmUniqueID>101238921</NlmUniqueID><ISSNLinking>1553-7366</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D012333">RNA, Messenger</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 3.4.21.-</RegistryNumber><NameOfSubstance UI="D053804">Granzymes</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><CommentsCorrectionsList><CommentsCorrections 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MajorTopicYN="N">Transcriptome</DescriptorName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2016</Year><Month>07</Month><Day>07</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2016</Year><Month>12</Month><Day>28</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2017</Year><Month>2</Month><Day>17</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2017</Year><Month>2</Month><Day>17</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2017</Year><Month>8</Month><Day>5</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>epublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">28207896</ArticleId><ArticleId IdType="doi">10.1371/journal.ppat.1006155</ArticleId><ArticleId IdType="pii">PPATHOGENS-D-16-01536</ArticleId><ArticleId 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