Chin-Yi Chu1,2, Xing Qiu3, Matthew N McCall3, Lu Wang3, Anthony Corbett3,4, Jeanne Holden-Wiltse3,4, Christopher Slaunwhite1,2, Alex Grier5, Steven R Gill5, Gloria S Pryhuber2, Ann R Falsey6,7, David J Topham5,8, Mary T Caserta2, Edward E Walsh6,7, Thomas J Mariani1,2. 1. Division of Neonatology and Pediatric Molecular and Personalized Medicine Program, University of Rochester Medical Center, Rochester, New York, USA. 2. Departments of Pediatrics, University of Rochester Medical Center, Rochester, New York, USA. 3. Department of Biostatistics and Computational Biology, University of Rochester Medical Center, Rochester, New York, USA. 4. Clinical and Translational Science Institute, University of Rochester Medical Center, Rochester, New York, USA. 5. Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, New York, USA. 6. Department of Medicine, University of Rochester Medical Center, Rochester, New York, USA. 7. Department of Medicine, Rochester General Hospital, Rochester, New York, USA. 8. David H. Smith Center for Vaccine Biology and Immunology, University of Rochester Medical Center, Rochester, New York, USA.
Abstract
BACKGROUND: Respiratory syncytial virus (RSV) is the leading cause of severe respiratory disease in infants. The causes and correlates of severe illness in the majority of infants are poorly defined. METHODS: We recruited a cohort of RSV-infected infants and simultaneously assayed the molecular status of their airways and the presence of airway microbiota. We used rigorous statistical approaches to identify gene expression patterns associated with disease severity and microbiota composition, separately and in combination. RESULTS: We measured comprehensive airway gene expression patterns in 106 infants with primary RSV infection. We identified an airway gene expression signature of severe illness dominated by excessive chemokine expression. We also found an association between Haemophilus influenzae, disease severity, and airway lymphocyte accumulation. Exploring the time of onset of clinical symptoms revealed acute activation of interferon signaling following RSV infection in infants with mild or moderate illness, which was absent in subjects with severe illness. CONCLUSIONS: Our data reveal that airway gene expression patterns distinguish mild/moderate from severe illness. Furthermore, our data identify biomarkers that may be therapeutic targets or useful for measuring efficacy of intervention responses.
BACKGROUND: Respiratory syncytial virus (RSV) is the leading cause of severe respiratory disease in infants. The causes and correlates of severe illness in the majority of infants are poorly defined. METHODS: We recruited a cohort of RSV-infected infants and simultaneously assayed the molecular status of their airways and the presence of airway microbiota. We used rigorous statistical approaches to identify gene expression patterns associated with disease severity and microbiota composition, separately and in combination. RESULTS: We measured comprehensive airway gene expression patterns in 106 infants with primary RSV infection. We identified an airway gene expression signature of severe illness dominated by excessive chemokine expression. We also found an association between Haemophilus influenzae, disease severity, and airway lymphocyte accumulation. Exploring the time of onset of clinical symptoms revealed acute activation of interferon signaling following RSV infection in infants with mild or moderate illness, which was absent in subjects with severe illness. CONCLUSIONS: Our data reveal that airway gene expression patterns distinguish mild/moderate from severe illness. Furthermore, our data identify biomarkers that may be therapeutic targets or useful for measuring efficacy of intervention responses.
Authors: Kohei Hasegawa; Rachel W Linnemann; Jonathan M Mansbach; Nadim J Ajami; Janice A Espinola; Joseph F Petrosino; Pedro A Piedra; Michelle D Stevenson; Ashley F Sullivan; Amy D Thompson; Carlos A Camargo Journal: Pediatr Infect Dis J Date: 2017-11 Impact factor: 2.129
Authors: Mary T Caserta; Xing Qiu; Brenda Tesini; Lu Wang; Amy Murphy; Anthony Corbett; David J Topham; Ann R Falsey; Jeanne Holden-Wiltse; Edward E Walsh Journal: J Infect Dis Date: 2017-03-01 Impact factor: 5.226
Authors: Matthew E Ritchie; Belinda Phipson; Di Wu; Yifang Hu; Charity W Law; Wei Shi; Gordon K Smyth Journal: Nucleic Acids Res Date: 2015-01-20 Impact factor: 16.971
Authors: Claire M Midgley; Amber K Haynes; Jason L Baumgardner; Christina Chommanard; Sara W Demas; Mila M Prill; Glen R Abedi; Aaron T Curns; John T Watson; Susan I Gerber Journal: J Infect Dis Date: 2017-08-01 Impact factor: 5.226
Authors: Alfonso Eduardo Alvarez; Fernando Augusto Lima Marson; Carmen Sílvia Bertuzzo; Juliana Cristina Santiago Bastos; Emilio Carlos Elias Baracat; Marcelo Barciela Brandão; Antônia Teresinha Tresoldi; Mariana Tresoldi das Neves Romaneli; Celize Cruz Bresciani Almeida; Therezinha de Oliveira; Patricia Godano Schlodtmann; Ester Corrêa; Maria Luisa Ferreira de Miranda; Marcelo Conrado Dos Reis; José Vicente De Pieri; Clarice Weis Arns; José Dirceu Ribeiro Journal: Gene Date: 2017-12-15 Impact factor: 3.688
Authors: Alex Grier; Ann L Gill; Haeja A Kessler; Anthony Corbett; Sanjukta Bandyopadhyay; James Java; Jeanne Holden-Wiltse; Ann R Falsey; David J Topham; Thomas J Mariani; Mary T Caserta; Edward E Walsh; Steven R Gill Journal: J Infect Dis Date: 2021-05-20 Impact factor: 5.226
Authors: Carter Merenstein; Guanxiang Liang; Samantha A Whiteside; Ana G Cobián-Güemes; Madeline S Merlino; Louis J Taylor; Abigail Glascock; Kyle Bittinger; Ceylan Tanes; Jevon Graham-Wooten; Layla A Khatib; Ayannah S Fitzgerald; Shantan Reddy; Amy E Baxter; Josephine R Giles; Derek A Oldridge; Nuala J Meyer; E John Wherry; John E McGinniss; Frederic D Bushman; Ronald G Collman Journal: mBio Date: 2021-08-17 Impact factor: 7.786
Authors: Lu Wang; Chin-Yi Chu; Matthew N McCall; Christopher Slaunwhite; Jeanne Holden-Wiltse; Anthony Corbett; Ann R Falsey; David J Topham; Mary T Caserta; Thomas J Mariani; Edward E Walsh; Xing Qiu Journal: BMC Med Genomics Date: 2021-02-25 Impact factor: 3.063
Authors: Matthew N McCall; Chin-Yi Chu; Lu Wang; Lauren Benoodt; Juilee Thakar; Anthony Corbett; Jeanne Holden-Wiltse; Christopher Slaunwhite; Alex Grier; Steven R Gill; Ann R Falsey; David J Topham; Mary T Caserta; Edward E Walsh; Xing Qiu; Thomas J Mariani Journal: PLoS Comput Biol Date: 2021-12-28 Impact factor: 4.779
Authors: Seesandra V Rajagopala; Nicole G Bakhoum; Suman B Pakala; Meghan H Shilts; Christian Rosas-Salazar; Annie Mai; Helen H Boone; Rendie McHenry; Shibu Yooseph; Natasha Halasa; Suman R Das Journal: Cell Rep Methods Date: 2021-10-25
Authors: Clarissa M Koch; Andrew D Prigge; Leah Setar; Kishore R Anekalla; Hahn Chi Do-Umehara; Hiam Abdala-Valencia; Yuliya Politanska; Avani Shukla; Jairo Chavez; Grant R Hahn; Bria M Coates Journal: Front Immunol Date: 2022-09-23 Impact factor: 8.786
Authors: Alex Grier; Ann L Gill; Haeja A Kessler; Anthony Corbett; Sanjukta Bandyopadhyay; James Java; Jeanne Holden-Wiltse; Ann R Falsey; David J Topham; Thomas J Mariani; Mary T Caserta; Edward E Walsh; Steven R Gill Journal: J Infect Dis Date: 2021-05-20 Impact factor: 5.226