Autophagy is a critically important component of cellular physiology, a catabolic process required to maintain cellular homeostasis. It eliminates molecules that are potentially damaging to the cell, such as reactive oxygen species and unfolded proteins. It is important in the immune response to microbes: dysregulated autophagy can compromise the activation of pro-survival pathways such as mitogen-activated protein kinases (MAPKs), signal transducer and activator of transcription 3 (STAT3), and nuclear factor-κB, as well as the production and release of cytokines. Autophagy also can eliminate damaged organelles (such as mitochondria) as well as intracellular pathogens, like viruses. Dysregulation of autophagy may predispose to autoimmune diseases, such as Alzheimer’s disease and Parkinson’s disease, or cancer.
Romeo et al. of the Sapienza University of Rome summarized the overall impact HHV-6 and other herpesviruses have on autophagy. The authors have previously shown that infection by HHV-6B leads to dysregulation of autophagy in monocytes (Granato et al 2019). The reduction of autophagy in monocytes can impair their differentiation into dendritic cells (Figure 1). The virus may have evolved this capability as a means of evading immune attack.
Romeo also reviews recent research finding that when HHV-6A infects neurons and astrocytes, it promotes neuroinflammation, the accumulation of amyloid-β and the hyperphosphorylation of tau protein—all cardinal features of Alzheimer’s disease. The authors have previously linked protein kinase R-like endoplasmic reticulum kinase (PERK) to the HHV-6A induced hyper-phosphorylation of tau-protein. PERK is hypothesized to active glycogen synthase kinase-3 beta, which has been known to phosphorylate tau protein. These effect of HHV-6 infection are summarized in Figure 1.
Figure 1: Representation of the impacts of autophagy by various herpesviruses - Romeo et al. 2020
Read the full article: Romeo 2020