title: Patient-based transcriptome-wide analysis identify interferon and ubiquination pathways as potential predictors of influenza A disease severity.
abstract: BACKGROUND
  The influenza A virus is an RNA virus that is responsible for seasonal epidemics worldwide with up to five million cases of severe illness and 500,000 deaths annually according to the World Health Organization estimates. The factors associated with severe diseases are not well defined, but more severe disease is more often seen among persons aged >65 years, infants, pregnant women, and individuals of any age with underlying health conditions.
  
  
  RESULTS
  Using gene expression microarrays, the transcriptomic profiles of influenza-infected patients with severe (N = 11), moderate (N = 40) and mild (N = 83) symptoms were compared with the febrile patients of unknown etiology (N = 73). We found that influenza-infected patients, regardless of their clinical outcomes, had a stronger induction of antiviral and cytokine responses and a stronger attenuation of NK and T cell responses in comparison with those with unknown etiology. More importantly, we found that both interferon and ubiquitination signaling were strongly attenuated in patients with the most severe outcomes in comparison with those with moderate and mild outcomes, suggesting the protective roles of these pathways in disease pathogenesis.
  The attenuation of interferon and ubiquitination pathways may associate with the clinical outcomes of influenza patients.
authors.affiliation: Genome Institute of Singapore, Singapore, Singapore.
authors.forename: Long Truong
authors.initials: LT
authors.lastname: Hoang
authors.affiliation: Infection Immunology, Respiratory Infections, Karolinska Institutet, Solna, Sweden.
authors.forename: Thomas
authors.initials: T
authors.lastname: Tolfvenstam
authors.affiliation: Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Eng Eong
authors.initials: EE
authors.lastname: Ooi
authors.affiliation: Genome Institute of Singapore, Singapore, Singapore.
authors.forename: Chiea Chuen
authors.initials: CC
authors.lastname: Khor
authors.affiliation: Genome Institute of Singapore, Singapore, Singapore.
authors.forename: Ahmand Nazri Mohamed
authors.initials: AN
authors.lastname: Naim
authors.affiliation: Genome Institute of Singapore, Singapore, Singapore.
authors.forename: Eliza Xin Pei
authors.initials: EX
authors.lastname: Ho
authors.affiliation: Genome Institute of Singapore, Singapore, Singapore.
authors.forename: Swee Hoe
authors.initials: SH
authors.lastname: Ong
authors.affiliation: National Hospital of Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Hanoi, Vietnam, and Centre for Tropical Medicine, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
authors.forename: Heiman F
authors.initials: HF
authors.lastname: Wertheim
authors.affiliation: National Hospital of Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Hanoi, Vietnam, and Centre for Tropical Medicine, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
authors.forename: Annette
authors.initials: A
authors.lastname: Fox
authors.affiliation: Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam.
authors.forename: Chau
authors.initials: C
authors.lastname: Van Vinh Nguyen
authors.affiliation: Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam.
authors.forename: Ngoc My
authors.initials: NM
authors.lastname: Nghiem
authors.affiliation: Children Hospital 2, Ho Chi Minh City, Vietnam.
authors.forename: Tuan Manh
authors.initials: TM
authors.lastname: Ha
authors.affiliation: Children Hospital 2, Ho Chi Minh City, Vietnam.
authors.forename: Anh
authors.initials: A
authors.lastname: Thi Ngoc Tran
authors.affiliation: National University Hospital, Singapore, Singapore.
authors.forename: Paul
authors.initials: P
authors.lastname: Tambayah
authors.affiliation: National University Hospital, Singapore, Singapore.
authors.forename: Raymond
authors.initials: R
authors.lastname: Lin
authors.affiliation: Bamrasnaradura Infectious Disease Institute, Nonthaburi, Thailand.
authors.forename: Chariya
authors.initials: C
authors.lastname: Sangsajja
authors.affiliation: Bamrasnaradura Infectious Disease Institute, Nonthaburi, Thailand.
authors.forename: Weerawat
authors.initials: W
authors.lastname: Manosuthi
authors.affiliation: Chest Disease Institute, Nonthaburi, Thailand.
authors.forename: Chareon
authors.initials: C
authors.lastname: Chuchottaworn
authors.affiliation: Chest Disease Institute, Nonthaburi, Thailand.
authors.forename: Piamlarp
authors.initials: P
authors.lastname: Sansayunh
authors.affiliation: Queen Sirikit National Institute of Child Health, Bangkok, Thailand.
authors.forename: Tawee
authors.initials: T
authors.lastname: Chotpitayasunondh
authors.affiliation: Queen Sirikit National Institute of Child Health, Bangkok, Thailand.
authors.forename: Piyarat
authors.initials: P
authors.lastname: Suntarattiwong
authors.affiliation: Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Kulkanya
authors.initials: K
authors.lastname: Chokephaibulkit
authors.affiliation: Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Pilaipan
authors.initials: P
authors.lastname: Puthavathana
authors.affiliation: The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam, and Centre for Tropical Medicine, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom; Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Menno D
authors.initials: MD
authors.lastname: de Jong
authors.affiliation: The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam, and Centre for Tropical Medicine, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Farrar
authors.affiliation: The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam, and Centre for Tropical Medicine, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
authors.forename: H Rogier
authors.initials: HR
authors.lastname: van Doorn
authors.affiliation: Genome Institute of Singapore, Singapore, Singapore.
authors.forename: Martin Lloyd
authors.initials: ML
authors.lastname: Hibberd
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019295:Computational Biology; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D009980:Influenza A virus / Q000276:immunology; D007251:Influenza, Human / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D007372:Interferons / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012720:Severity of Illness Index; D015398:Signal Transduction; D059467:Transcriptome; D054875:Ubiquitination; D055815:Young Adult
chemical_list: D007372:Interferons