Search for varicella zoster virus and herpes simplex virus-1 in normal human cerebral arteries

Abstract

Virological confirmation of varicella zoster virus (VZV) vasculopathy is provided by presence of virus in cerebral arteries, frequently associated with inflammation. Yet cerebral arteries from normal subjects have never been studied for VZV DNA or antigen. We analyzed 63 human cerebral arteries from 45 subjects for VZV DNA and antigen, control herpes simplex virus (HSV)-1 DNA and antigen and leukocyte-specific CD45 antigen. No cerebral arteries contained VZV or HSV-1 DNA or antigen; 8 arteries from 7 subjects contained leukocytes expressing CD45. Thus, the presence of VZV antigen in cerebral arteries of patients with stroke is likely to be clinically significant.

Varicella zoster virus (VZV) in cerebral arteries of subjects at high risk for VZV reactivation

“…When VZV antigen was detected, VZV-positive sections were scraped with a scalpel, pooled if more than one section was positive and placed into 200 μl lysis buffer with proteinase K (DNeasy Blood and Tissue Kit; Qiagen; Germantown, MD), followed by DNA extraction per the manufacturer’s protocol and quantitative PCR analysis as described [3]. Positive and negative controls were provided by amplification of serial dilutions of known quantities of VZV DNA and by omission of VZV DNA from the PCR, respectively.…”

“…In particular, there is a 30% increased risk of stroke within one year after zoster [2]. A recent study of 63 human cerebral arteries from 45 subjects with no history of transient ischemic attacks or stroke showed no VZV DNA in any arteries, and immunohistochemical analysis of single sections from formalin-fixed, paraffin-embedded arteries revealed no VZV antigen [3]. Importantly, a similar study detected both VZV DNA and antigen in the cerebral artery of a diabetic subject with no history of TIAs or stroke [4], which is not surprising since diabetic subjects are at greater risk for zoster [5].…”

Varicella zoster virus vasculopathy: The expanding clinical spectrum and pathogenesis

“…Our studies of intracerebral VZV vasculopathy included examination of 63 cerebral arteries from 45 normal subjects (Nagel et al, 2013d). No VZV antigen was found when one formalin-fixed, paraffin-embedded (FFPE) section was analyzed from each sample, and no VZV DNA was detected by PCR from 20 mg of total DNA from each sample.…”

Varicella zoster virus vasculopathy: clinical features and pathogenesis

“…In a related study to determine the frequency of VZV antigen in the arteries of normal subjects, we analyzed 63 human cerebral arteries from 45 subjects for VZV DNA and antigen, control herpes simplex virus (HSV)-1 DNA and antigen, and leukocyte-specific CD45 antigen (Nagel et al 2013c). No cerebral arteries contained VZV or HSV-1 DNA or antigen, while 8 arteries from 7 subjects contained CD45+ leukocytes.…”