Publications by authors named "Ann Wyborny"

4 Publications

  • Page 1 of 1

Varicella zoster virus vasculopathy: The expanding clinical spectrum and pathogenesis.

J Neuroimmunol 2017 07 18;308:112-117. Epub 2017 Mar 18.

Department of Neurology, University of Colorado School of Medicine, Aurora, CO 80045, USA. Electronic address:

Varicella zoster virus (VZV) is a ubiquitous, human alphaherpesvirus that produces varicella on primary infection then becomes latent in ganglionic neurons along the entire neuraxis. In elderly and immunocompromised individuals, VZV reactivates and travels along nerve fibers peripherally resulting in zoster. However, VZV can also spread centrally and infect cerebral and extracranial arteries (VZV vasculopathy) to produce transient ischemic attacks, stroke, aneurysm, sinus thrombosis and giant cell arteritis, as well as granulomatous aortitis. The mechanisms of virus-induced pathological vascular remodeling are not fully elucidated; however, recent studies suggest that inflammation and dysregulation of programmed death ligand-1 play a significant role.
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http://dx.doi.org/10.1016/j.jneuroim.2017.03.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5489071PMC
July 2017

Differential regulation of matrix metalloproteinases in varicella zoster virus-infected human brain vascular adventitial fibroblasts.

J Neurol Sci 2015 Nov 16;358(1-2):444-6. Epub 2015 Sep 16.

Department of Neurology, University of Colorado School of Medicine, Aurora, CO, USA; Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, CO, USA.

Upon reactivation, varicella zoster virus (VZV) spreads transaxonally, infects cerebral arteries and causes ischemic or hemorrhagic stroke, as well as aneurysms. The mechanism(s) of VZV-induced aneurysm formation is unknown. However, matrix metalloproteinases (MMPs), which digest extracellular structural proteins in the artery wall, play a role in cerebral and aortic artery aneurysm formation and rupture. Here, we examined the effect of VZV infection on expression of MMP-1, -2, -3, and -9 in primary human brain vascular adventitial fibroblasts (BRAFS). At 6 days post-infection, VZV- and mock-infected BRAFs were analyzed for mRNA levels of MMP-1, -2, -3 and -9 by RT-PCR and for corresponding total intra- and extracellular protein levels by multiplex ELISA. The activity of MMP-1 was also measured in a substrate cleavage assay. Compared to mock-infected BRAFs, MMP-1, MMP-3 and MMP-9 transcripts, cell lysate protein and conditioned supernatant protein were all increased in VZV-infected BRAFs, whereas MMP-2 transcripts, cell lysate protein and conditioned supernatant protein were decreased. MMP-1 from the conditioned supernatant of VZV-infected BRAFs showed increased cleavage activity on an MMP-1-specific substrate compared to mock-infected BRAFs. Differential regulation of MMPs in VZV-infected BRAFs may contribute to aneurysm formation in VZV vasculopathy.
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http://dx.doi.org/10.1016/j.jns.2015.09.349DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4628845PMC
November 2015

Inhibition of phosphorylated-STAT1 nuclear translocation and antiviral protein expression in human brain vascular adventitial fibroblasts infected with varicella-zoster virus.

J Virol 2014 Oct 23;88(19):11634-7. Epub 2014 Jul 23.

Department of Neurology, University of Colorado School of Medicine, Aurora, Colorado, USA Department of Microbiology, University of Colorado School of Medicine, Aurora, Colorado, USA.

In varicella-zoster virus (VZV)-infected primary human brain vascular adventitial fibroblasts (BRAFs), levels of beta interferon (IFN-β,) STAT1, and STAT2 transcripts as well as STAT1 and STAT2 protein were decreased. IFN-α transcript levels were increased but not secreted IFN-α protein levels. Compared to IFN-α-treated control results, in VZV-infected BRAFs, phosphorylated STAT1 did not translocate to the nucleus, resulting in impaired downstream expression of interferon-inducible antiviral Mx1. Overall, VZV interference with the type I interferon pathway may promote virus persistence in cerebral arteries.
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http://dx.doi.org/10.1128/JVI.01945-14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4178816PMC
October 2014

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

J Neurovirol 2013 Apr 1;19(2):181-5. Epub 2013 Mar 1.

Department of Neurology, University of Colorado School of Medicine, 12700 E. 19th Avenue, Mail Stop B182, Aurora, CO 80045, USA.

Virological confirmation of varicella zoster virus (VZV) vasculopathy is provided by presence of virus in the 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; eight arteries from seven subjects contained leukocytes expressing CD45. Thus, the presence of VZV antigen in cerebral arteries of patients with stroke is likely to be clinically significant.
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http://dx.doi.org/10.1007/s13365-013-0155-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3644002PMC
April 2013