Alphaherpesvirus-induced activation of plasmacytoid dendritic cells depends on the viral glycoprotein gD and is inhibited by non-infectious light particles

Plasmacytoid dendritic cells (pDC) are important innate immune cells during the onset of viral infections as they are specialized in the production of massive amounts of antiviral type I interferon (IFN). Alphaherpesviruses such as herpes simplex virus (HSV) or pseudorabies virus (PRV) are double st...

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Bibliographic Details
Published in:PLoS pathogens 2021-11, Vol.17 (11), p.e1010117-e1010117
Main Authors: Delva, Jonas L, Van Waesberghe, Cliff, Klupp, Barbara G, Mettenleiter, Thomas C, Favoreel, Herman W
Format: Article
Language:English
Subjects:
Acidification
Amino acids
Analysis
Animals
Antibiotics
Antibodies
Bacterial proteins
Biology and Life Sciences
Blood
Cell activation
Dendritic cells
Dendritic Cells - immunology
Dendritic Cells - metabolism
Dendritic Cells - virology
Deoxyribonucleic acid
Distribution
DNA
DNA viruses
Glycoproteins
Herpes simplex
Herpes Simplex - immunology
Herpes Simplex - metabolism
Herpes Simplex - virology
Herpes viruses
Herpesvirus 1, Human - physiology
Herpesvirus 1, Suid - physiology
Host-virus relationships
Immune system
Infections
Interferon
Interferon Type I - metabolism
Male
Medicine and Health Sciences
Pathogens
Physiological aspects
Proteins
Pseudorabies - immunology
Pseudorabies - metabolism
Pseudorabies - virology
Research and Analysis Methods
Sodium
Stimulators
Swine
Testis - immunology
Testis - metabolism
Testis - virology
Veterinary medicine
Viral Envelope Proteins - genetics
Viral Envelope Proteins - metabolism
Virion - physiology
Virions
Viruses
α-Interferon
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Summary:Plasmacytoid dendritic cells (pDC) are important innate immune cells during the onset of viral infections as they are specialized in the production of massive amounts of antiviral type I interferon (IFN). Alphaherpesviruses such as herpes simplex virus (HSV) or pseudorabies virus (PRV) are double stranded DNA viruses and potent stimulators of pDC. Detailed information on how PRV activates porcine pDC is lacking. Using PRV and porcine primary pDC, we report here that PRV virions, so-called heavy (H-)particles, trigger IFNα production by pDC, whereas light (L-) particles that lack viral DNA and capsid do not. Activation of pDC requires endosomal acidification and, importantly, depends on the PRV gD envelope glycoprotein and O-glycosylations. Intriguingly, both for PRV and HSV-1, we found that L-particles suppress H-particle-mediated activation of pDC, a process which again depends on viral gD. This is the first report describing that gD plays a critical role in alphaherpesvirus-induced pDC activation and that L-particles directly interfere with alphaherpesvirus-induced IFNα production by pDC.
ISSN:1553-7374
1553-7366
1553-7374
DOI:10.1371/journal.ppat.1010117