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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 J+Virol
2017 ; 91
(7
): ä Nephropedia Template TP
gab.com Text
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The Pseudorabies Virus Glycoprotein gE/gI Complex Suppresses Type I Interferon
Production by Plasmacytoid Dendritic Cells
#MMPMID28122975
Lamote JAS
; Kestens M
; Van Waesberghe C
; Delva J
; De Pelsmaeker S
; Devriendt B
; Favoreel HW
J Virol
2017[Apr]; 91
(7
): ä PMID28122975
show ga
Plasmacytoid dendritic cells (pDC) play a central role in the antiviral immune
response, both in the innate response and in shaping the adaptive response,
mainly because of their ability to produce massive amounts of type I interferon
(TI-IFN). Here, we report that cells infected with the live attenuated Bartha
vaccine strain of porcine alphaherpesvirus pseudorabies virus (PRV) trigger a
dramatically increased TI-IFN response by porcine primary pDC compared to cells
infected with wild-type PRV strains (Becker and Kaplan). Since Bartha is one of
the relatively few examples of a highly successful alphaherpesvirus vaccine,
identification of factors that may contribute to its efficacy may provide
insights for the rational design of other alphaherpesvirus vaccines. The Bartha
vaccine genome displays several mutations compared to the genome of wild-type PRV
strains, including a large deletion in the unique short (US) region, encompassing
the glycoprotein E (gE), gI, US9, and US2 genes. Using recombinant PRV Becker
strains harboring the entire Bartha US deletion or single mutations in the four
affected US genes, we demonstrate that the absence of the viral gE/gI complex
contributes to the observed increased IFN-? response. Furthermore, we show that
the absence of gE leads to an enhanced extracellular signal-regulated kinase 1/2
(ERK1/2) phosphorylation in pDC, which correlates with a higher TI-IFN production
by pDC. In conclusion, the PRV Bartha vaccine strain triggers strongly increased
TI-IFN production by porcine pDC. Our data further indicate that the gE/gI
glycoprotein complex suppresses TI-IFN production by pDC, which represents the
first alphaherpesvirus factor that suppresses pDC activity.IMPORTANCE Several
alphaherpesviruses, including herpes simpex virus, still lack effective vaccines.
However, the highly successful Bartha vaccine has contributed substantially to
eradication of the porcine alphaherpesvirus pseudorabies virus (PRV) in several
countries. The impact of Bartha on the immune response is still poorly
understood. Type I interferon (TI-IFN)-producing plasmacytoid dendritic cells
(pDC) may play an important role in vaccine development. Here, we show that
Bartha elicits a dramatically increased type I interferon (TI-IFN) response in
primary porcine pDC compared to wild-type strains. In addition, we found that the
gE/gI complex, which is absent in Bartha, inhibits the pDC TI-IFN response. This
is the first description of an immune cell type that is differentially affected
by Bartha versus wild-type PRV and is the first report describing an
alphaherpesvirus protein that inhibits the TI-IFN response by pDC. These data may
therefore contribute to the rational design of other alphaherpesvirus vaccines.