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Stage-specific IFN-induced and IFN gene expression reveal convergence of type I and type II IFN and highlight their role in both acute and chronic stage of pathogenic SIV infection.

Abstract Interferons (IFNs) play a major role in controlling viral infections including HIV/SIV infections. Persistent up-regulation of interferon stimulated genes (ISGs) is associated with chronic immune activation and progression in SIV/HIV infections, but the respective contribution of different IFNs is unclear. We analyzed the expression of IFN genes and ISGs in tissues of SIV infected macaques to understand the respective roles of type I and type II IFNs. Both IFN types were induced in lymph nodes during early stage of primary infection and to some extent in rectal biopsies but not in PBMCs. Induction of Type II IFN expression persisted during the chronic phase, in contrast to undetectable induction of type I IFN expression. Global gene expression analysis with a major focus on ISGs revealed that at both acute and chronic infection phases most differentially expressed ISGs were inducible by both type I and type II IFNs and displayed the highest increases, indicating strong convergence and synergy between type I and type II IFNs. The analysis of functional signatures of ISG expression revealed temporal changes in IFN expression patterns identifying phase-specific ISGs. These results suggest that IFN-γ strongly contribute to shape ISG upregulation in addition to type I IFN.
PMID
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Authors

Mayor MeshTerms

Gene Expression

Keywords
Journal Title plos one
Publication Year Start




PMID- 29324751
OWN - NLM
STAT- MEDLINE
DCOM- 20180206
LR  - 20180206
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 13
IP  - 1
DP  - 2018
TI  - Stage-specific IFN-induced and IFN gene expression reveal convergence of type I
      and type II IFN and highlight their role in both acute and chronic stage of
      pathogenic SIV infection.
PG  - e0190334
LID - 10.1371/journal.pone.0190334 [doi]
AB  - Interferons (IFNs) play a major role in controlling viral infections including
      HIV/SIV infections. Persistent up-regulation of interferon stimulated genes
      (ISGs) is associated with chronic immune activation and progression in SIV/HIV
      infections, but the respective contribution of different IFNs is unclear. We
      analyzed the expression of IFN genes and ISGs in tissues of SIV infected macaques
      to understand the respective roles of type I and type II IFNs. Both IFN types
      were induced in lymph nodes during early stage of primary infection and to some
      extent in rectal biopsies but not in PBMCs. Induction of Type II IFN expression
      persisted during the chronic phase, in contrast to undetectable induction of type
      I IFN expression. Global gene expression analysis with a major focus on ISGs
      revealed that at both acute and chronic infection phases most differentially
      expressed ISGs were inducible by both type I and type II IFNs and displayed the
      highest increases, indicating strong convergence and synergy between type I and
      type II IFNs. The analysis of functional signatures of ISG expression revealed
      temporal changes in IFN expression patterns identifying phase-specific ISGs.
      These results suggest that IFN-gamma strongly contribute to shape ISG
      upregulation in addition to type I IFN.
FAU - Echebli, Nadia
AU  - Echebli N
AD  - CEA, Universite Paris Sud, INSERM U1184, Immunology of Viral Infections and
      Autoimmune Diseases (IMVA), IDMIT Department / IBFJ, Fontenay-aux-Roses, France.
FAU - Tchitchek, Nicolas
AU  - Tchitchek N
AD  - CEA, Universite Paris Sud, INSERM U1184, Immunology of Viral Infections and
      Autoimmune Diseases (IMVA), IDMIT Department / IBFJ, Fontenay-aux-Roses, France.
FAU - Dupuy, Stephanie
AU  - Dupuy S
AD  - CEA, Universite Paris Sud, INSERM U1184, Immunology of Viral Infections and
      Autoimmune Diseases (IMVA), IDMIT Department / IBFJ, Fontenay-aux-Roses, France.
FAU - Bruel, Timothee
AU  - Bruel T
AD  - CEA, Universite Paris Sud, INSERM U1184, Immunology of Viral Infections and
      Autoimmune Diseases (IMVA), IDMIT Department / IBFJ, Fontenay-aux-Roses, France.
FAU - Peireira Bittencourt Passaes, Caroline
AU  - Peireira Bittencourt Passaes C
AD  - CEA, Universite Paris Sud, INSERM U1184, Immunology of Viral Infections and
      Autoimmune Diseases (IMVA), IDMIT Department / IBFJ, Fontenay-aux-Roses, France.
FAU - Bosquet, Nathalie
AU  - Bosquet N
AD  - CEA, Universite Paris Sud, INSERM U1184, Immunology of Viral Infections and
      Autoimmune Diseases (IMVA), IDMIT Department / IBFJ, Fontenay-aux-Roses, France.
FAU - Le Grand, Roger
AU  - Le Grand R
AD  - CEA, Universite Paris Sud, INSERM U1184, Immunology of Viral Infections and
      Autoimmune Diseases (IMVA), IDMIT Department / IBFJ, Fontenay-aux-Roses, France.
FAU - Bourgeois, Christine
AU  - Bourgeois C
AD  - CEA, Universite Paris Sud, INSERM U1184, Immunology of Viral Infections and
      Autoimmune Diseases (IMVA), IDMIT Department / IBFJ, Fontenay-aux-Roses, France.
FAU - Favier, Benoit
AU  - Favier B
AD  - CEA, Universite Paris Sud, INSERM U1184, Immunology of Viral Infections and
      Autoimmune Diseases (IMVA), IDMIT Department / IBFJ, Fontenay-aux-Roses, France.
FAU - Cheynier, Remi
AU  - Cheynier R
AD  - Cytokines and Viral Infections, Immunology Infection and Inflammation Department,
      Institut Cochin, INSERM U1016, Paris, France.
AD  - CNRS, UMR8104, Paris, France.
AD  - Universite Paris Descartes, Paris, France.
FAU - Lambotte, Olivier
AU  - Lambotte O
AD  - CEA, Universite Paris Sud, INSERM U1184, Immunology of Viral Infections and
      Autoimmune Diseases (IMVA), IDMIT Department / IBFJ, Fontenay-aux-Roses, France.
AD  - APHP, Service de Medecine Interne-Immunologie Clinique, Hopitaux Universitaires
      Paris Sud, Le Kremlin-Bicetre, France.
FAU - Vaslin, Bruno
AU  - Vaslin B
AUID- ORCID: 0000-0003-1758-9037
AD  - CEA, Universite Paris Sud, INSERM U1184, Immunology of Viral Infections and
      Autoimmune Diseases (IMVA), IDMIT Department / IBFJ, Fontenay-aux-Roses, France.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180111
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Interferon Type I)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Acute Disease
MH  - Animals
MH  - Chronic Disease
MH  - *Gene Expression
MH  - Interferon Type I/*genetics
MH  - Interferon-gamma/*genetics
MH  - Macaca fascicularis
MH  - Simian Acquired Immunodeficiency Syndrome/*immunology
MH  - Simian Immunodeficiency Virus/immunology/physiology
MH  - Transcriptome
MH  - Virus Replication
PMC - PMC5764266
EDAT- 2018/01/13 06:00
MHDA- 2018/02/07 06:00
CRDT- 2018/01/12 06:00
PHST- 2017/09/26 00:00 [received]
PHST- 2017/12/12 00:00 [accepted]
PHST- 2018/01/12 06:00 [entrez]
PHST- 2018/01/13 06:00 [pubmed]
PHST- 2018/02/07 06:00 [medline]
AID - 10.1371/journal.pone.0190334 [doi]
AID - PONE-D-17-34856 [pii]
PST - epublish
SO  - PLoS One. 2018 Jan 11;13(1):e0190334. doi: 10.1371/journal.pone.0190334.
      eCollection 2018.