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Research Letter
Jan 2012

Varicella-Zoster Virus Expression in the Cerebral Arteries of Diabetic Subjects

Author Affiliations

Author Affiliations: Departments of Neurology (Drs Nagel and Gilden, Messrs Traktinskiy and Choe, and Ms Rempel) and Microbiology (Dr Gilden), University of Colorado School of Medicine, Aurora.

Arch Neurol. 2012;69(1):142-144. doi:10.1001/archneur.69.1.142

Primary varicella-zoster virus (VZV) infection causes varicella (chickenpox), after which VZV becomes latent in ganglionic neurons along the entire neuraxis. A decline in cell-mediated immunity to VZV in elderly and immunocompromised individuals results in zoster (shingles). Within the first year after herpes zoster, there is a 30% increased risk of stroke.1,2 Approximately one-third of patients with VZV vasculopathy do not have zoster rash and diabetic patients are at greater risk for both zoster3 and stroke; therefore, we examined the cerebral arteries of 4 diabetic subjects for the presence of VZV DNA and antigen.

Cerebral arteries obtained from 4 subjects with diabetes less than 24 hours after they died were analyzed. All subjects had diabetes and no history of zoster infection, transient ischemic attacks, stroke, or immunosuppression. Subject 1 was a 51-year-old woman with hypertension who died of drug overdose; subject 2 was a 60-year-old man with systemic lupus erythematosus who died of asphyxia; subject 3 was a 51-year-old woman who died of myocardial infarction; and subject 4 was a 60-year-old woman with melanoma, hypertension, and hyperlipidemia who died of a drug overdose. An average of 17 pieces of cerebral arteries (about 10 mm/piece) from each subject were analyzed (total of 68). Each piece was cut in half. DNA was extracted from the first half and analyzed by real-time polymerase chain reaction for the presence of VZV DNA using VZV gene 63 specific primers (gene 63-forward 5′-GCTTACGCGCTACTTTAATGGAA-3′ and gene 63-reverse 5′-GCCTCAATGAACCCGTCTTC-3′) and probes (gene 63 5′-TGTCCCATCGACCCCCTCGG-3′).4 Positive controls were provided by amplification of serial dilutions of known quantities of VZV DNA. Negative controls were provided by omission of VZV DNA from the polymerase chain reaction, which was performed 3 times. The other half was formalin-fixed and paraffin-embedded. If VZV DNA was detected, immunohistochemical analysis was performed on the remaining formalin-fixed, paraffin-embedded arterial sections for VZV gene 63 protein and leukocyte CD45 antigen. Limited arterial tissue precluded a search for additional antigens. Slides were viewed by Nikon Eclipse E800 microscopy with AxioVision digital imaging software (Carl Zeiss MicroImaging GmbH).

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