Table 2 Viral induced molecular/cellular changes related to PD pathology
ThemeCondition
PDHSV-IInfluenza A
Inflammation
Glial cellsActivated microglia and astrogliosis in PD midbrain [130,131]↑ microglia in HSV-I infected ependymal [132]H1N1 ↑ astrogliosis and activated microglia in SN and VTA [133]
T cellsT-cell modulation and recognition of α-synuclein epitopes in PD [93,134]Exhausted T cells in HSV-I infected brain stem and TG express HSV-I epitope [87,89,132]H5N1 causes excessive peripheral T-cell activation [92]
Cytokines↑ CSF and peripheral cytokines in PD [110,111]T-cell associated cytokines ↑ in HSV-infected TG [88,90,91]H5N1 ↑ astrocyte/neuronal cytokines [135,136]
Autophagy
DisruptionAutophagic and lysosomal defects in PD neurones [137,138]PKR inhibition disrupts autophagy/autophagosome formation [139,140,141]PKR inhibition and autophagosome/lysosome fusion blocked [142,143]
Synapse
ProteinsRedistribution of synaptic proteins in PD models [144,145]↓ synapsin-1 and synaptophysin in murine cortical neurones [146,147]H5N1 inhibits PSD-95; SNAP25 differentially expressed in neonatal infection [148,149]
Activity↓ synaptic connectivity and glutamatergic synapse loss in PD models [150,151]Reduced NMDAR and synaptic activity in HSE patients [146,152]↓ neuronal excitatory synaptic activity and amplitude [153]
  • As detailed above, multiple parallels can be drawn between PD pathology and the potential molecular and cellular consequences of HSV-I/influenza A infection. Abbreviations: NMDAR, N-methyl-d-aspartate receptor; PKR, protein kinase R; PSD-95, post-synaptic density protein-95; SNAP25, synaptosomal-associated protein 25; VTA, ventral tegmental area.