PMID- 33522421
OWN - NLM
STAT- MEDLINE
DCOM- 20210930
LR  - 20210930
IS  - 2150-5608 (Electronic)
IS  - 2150-5594 (Print)
IS  - 2150-5594 (Linking)
VI  - 12
IP  - 1
DP  - 2021 Dec
TI  - Hemagglutinin protein of Peste des Petits Ruminants virus (PPRV) activates the 
      innate immune response via Toll-like receptor 2 signaling.
PG  - 690-703
LID - 10.1080/21505594.2021.1882246 [doi]
AB  - The toll-like receptor (TLR) family comprises both cell-surface and intracellular 
      receptors that recognize different types of pathogen-associated molecular 
      patterns (PAMPs) leading to the production of pro-inflammatory cytokines and 
      subsequent development of adaptive immunity. TLR2 is a cell-surface receptor 
      initially thought to act as a bacterial sentinel but also shown to recognize a 
      number of viral glycoproteins. In this study, we sought to characterize the role 
      of TLR2 in the activation of the immune response by peste des petits ruminants 
      virus (PPRV), a morbillivirus of the Paramixoviridae family that causes an acute, 
      highly contagious disease in goats and sheep. Using human embryonic kidney (HEK) 
      293 cells stably expressing human (h)TLR2 but lacking any other TLR, we found 
      that PPRV induces IL-8 production in a dose-dependent manner. That activation is 
      only observed in cells expressing hTLR2 and is greatly reduced when the receptor 
      is blocked by pretreatment with specific antibody. We identified hemagglutinin 
      (H) as the viral protein responsible of TLR2 activation by performing the same 
      assays with purified recombinant mammalian-expressed H protein. Exogenous 
      addition of recombinant H protein to cell culture induces high levels of 
      interleukin (IL)-8 only in TLR2-expressing cells. Moreover, H engagement on TLR2 
      in the monocytic cell line THP-1 activates extracellular-signal-regulated kinase 
      (ERK) signaling. Stimulation of primary ovine dendritic cells with either 
      inactivated PPRV or purified recombinant H protein results in transcription of 
      pro-inflammatory cytokines and the secretion of the Th1-polarizing cytokine 
      IL-12. The role of these host immune mechanisms in the control of PPR is 
      discussed.
FAU - Rojas, Jose M
AU  - Rojas JM
AD  - Centro de Investigacion en Sanidad Animal (CISA-INIA), Instituto Nacional de 
      Investigacion Agraria y Alimentaria , Madrid, Spain.
FAU - Pascual, Elena
AU  - Pascual E
AD  - Centro de Investigacion en Sanidad Animal (CISA-INIA), Instituto Nacional de 
      Investigacion Agraria y Alimentaria , Madrid, Spain.
FAU - Wattegedera, Sean R
AU  - Wattegedera SR
AD  - Moredun Research Institute , Edinburgh, Scotland, UK.
FAU - Avia, Miguel
AU  - Avia M
AD  - Centro de Investigacion en Sanidad Animal (CISA-INIA), Instituto Nacional de 
      Investigacion Agraria y Alimentaria , Madrid, Spain.
FAU - Santiago, Cesar
AU  - Santiago C
AD  - Centro Nacional de Biotecnologia-CSIC , Madrid, Spain.
FAU - Martin, Veronica
AU  - Martin V
AD  - Centro de Investigacion en Sanidad Animal (CISA-INIA), Instituto Nacional de 
      Investigacion Agraria y Alimentaria , Madrid, Spain.
FAU - Entrican, Gary
AU  - Entrican G
AD  - College of Medicine and Veterinary Medicine, University of Edinburgh , Edinburgh, 
      Scotland, UK.
FAU - Sevilla, Noemi
AU  - Sevilla N
AUID- ORCID: 0000-0003-0118-0376
AD  - Centro de Investigacion en Sanidad Animal (CISA-INIA), Instituto Nacional de 
      Investigacion Agraria y Alimentaria , Madrid, Spain.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Virulence
JT  - Virulence
JID - 101531386
RN  - 0 (Cytokines)
RN  - 0 (Hemagglutinins, Viral)
RN  - 0 (TLR2 protein, human)
RN  - 0 (Toll-Like Receptor 2)
SB  - IM
MH  - Animals
MH  - Cytokines/immunology
MH  - Dendritic Cells/drug effects/immunology/virology
MH  - HEK293 Cells
MH  - Hemagglutinins, Viral/genetics/*immunology/pharmacology
MH  - Humans
MH  - Immunity, Innate/*drug effects
MH  - Peste-des-petits-ruminants virus/*genetics/*immunology
MH  - Sheep
MH  - Signal Transduction/drug effects/*immunology
MH  - THP-1 Cells
MH  - Toll-Like Receptor 2/*genetics/*metabolism
PMC - PMC7889028
OTO - NOTNLM
OT  - ERK
OT  - TLR2
OT  - dendritic cells
OT  - hemagglutinin
OT  - interleukin-8
OT  - macrophage
OT  - monocyte
OT  - morbillivirus
COIS- The authors declare no conflict of interest
EDAT- 2021/02/02 06:00
MHDA- 2021/10/01 06:00
PMCR- 2021/02/12
CRDT- 2021/02/01 08:43
PHST- 2021/02/02 06:00 [pubmed]
PHST- 2021/10/01 06:00 [medline]
PHST- 2021/02/01 08:43 [entrez]
PHST- 2021/02/12 00:00 [pmc-release]
AID - 1882246 [pii]
AID - 10.1080/21505594.2021.1882246 [doi]
PST - ppublish
SO  - Virulence. 2021 Dec;12(1):690-703. doi: 10.1080/21505594.2021.1882246.