Differential Reliance on Autophagy for Protection from HSV Encephalitis between Newborns and Adults


Disease after infection with a pathogen results from an intersection between the infectious agent and the host. Newborns are particularly susceptible to infectious illness compared to adults, and HSV infection commonly results in devastating encephalitis. We studied the interaction of HSV with the type I interferon pathway and found that a specific activity of the viral protein γ34.5, which counters host autophagy to promote encephalitis in adults, was not required to cause disease in newborns. Furthermore, autophagy was not inhibited by HSV in the neonate and was not activated by type I interferon signaling, unlike in the adult. Activated autophagy was associated with increased apoptosis, which may contribute to the increased pathology in newborns. Our findings reveal development-specific differences in the pathogenesis of HSV encephalitis, including a distinct role for autophagy in the neonatal brain.


Vyšlo v časopise: Differential Reliance on Autophagy for Protection from HSV Encephalitis between Newborns and Adults. PLoS Pathog 11(1): e32767. doi:10.1371/journal.ppat.1004580
Kategorie: Research Article
prolekare.web.journal.doi_sk: 10.1371/journal.ppat.1004580

Souhrn

Disease after infection with a pathogen results from an intersection between the infectious agent and the host. Newborns are particularly susceptible to infectious illness compared to adults, and HSV infection commonly results in devastating encephalitis. We studied the interaction of HSV with the type I interferon pathway and found that a specific activity of the viral protein γ34.5, which counters host autophagy to promote encephalitis in adults, was not required to cause disease in newborns. Furthermore, autophagy was not inhibited by HSV in the neonate and was not activated by type I interferon signaling, unlike in the adult. Activated autophagy was associated with increased apoptosis, which may contribute to the increased pathology in newborns. Our findings reveal development-specific differences in the pathogenesis of HSV encephalitis, including a distinct role for autophagy in the neonatal brain.


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Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

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PLOS Pathogens


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