Amyloid Potentially Involved in VZV Vasculopathy


Varicella zoster virus (VZV) vasculopathy may be an amyloid disease, according to a study published in Neurology Neuroimmunology & Neuroinflammation. The researchers based this conclusion on the analysis of VZV-infected primary human brain vascular adventitial fibroblasts (HBVAFs), which are among the first arterial cells infected in VZV vasculopathy.

According to the investigators, patients with VZV vasculopathy have increased amyloid in cerebrospinal fluid compared to stroke controls, as well as increased amylin and anti-VZV antibodies. The study was designed to determine whether VZV-infected HBVAFs are a potential source of amyloid that could disrupt vasculature and cause inflammation. To conduct the study, Mock- and VZV-infected quiescent HBVAFs were harvested 3 days following VZV infection. Targeted RNA sequencing of the whole-human transcriptome was conducted, followed by gene set enrichment and pathway analysis.

The analysis showed that, compared to the control, VZV-infected HBVAFs had significantly enriched gene expression pathways involved in vascular remodeling and vascular diseases. Further, the investigators identified significantly enriched pathways involved in amyloid-associated diseases, including diabetes mellitus, amyloidosis, and Alzheimer disease, as well as tauopathy and progressive neurologic disorder.

“Given the evidence that VZV vasculopathy may be an amyloid-associated disease, by extension, VZV vasculopathy may also increase the amyloid burden of other amyloid-associated diseases, such as Alzheimer disease, and accelerate clinical decline,” the researchers said in the study. “This is further supported by epidemiologic studies showing that VZV reactivation (herpes zoster) increases the risk of dementia, and antiviral therapy reduces the risk, and increased the risk of neovascular macular degeneration, both characterized by Aβ42/amylin and Aβ42 aggregates, respectively.”

Based on their findings, the investigators suggest that future studies examine VZV antigen and amyloid in postmortem virus-infected arteries from patients with VZV vasculopathy. They also concluded that, in patients with amyloid-associated diseases, VZV reactivation should be considered a potential accelerator of disease progression. These patients could potentially benefit from zoster vaccination to prevent the virus from reactivating, or from rapid antiviral therapy during reactivation.

“Overall, there is mounting evidence that VZV vasculopathy is an amyloid-associated disease and virus-induced deposition of amyloid may serve as a nidus for persistent inflammation and cytotoxicity, depending on host and environmental factors that contribute to efficient or deficient amyloid clearance,” the investigators wrote.


Bubak AN, Como CN, Hassell JE, et al. Targeted RNA sequencing of VZV-infected brain vascular adventitial fibroblasts indicates that amyloid may be involved in VZV vasculopathy. Neurol Neuroimmunol Neuroinflamm. 2022 Jan; 9(1): e1103. doi: 10.1212/NXI.0000000000001103

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