Targeted RNA Sequencing of Formalin-Fixed, Paraffin-Embedded Temporal Arteries From Giant Cell Arteritis Cases Reveals Viral Signatures

Neurol Neuroimmunol Neuroinflamm. 2021 Sep 7;8(6):e0178. doi: 10.1212/NXI.0000000000001078. Print 2021 Nov.


Background and objectives: Varicella zoster virus (VZV) antigen has been detected in temporal arteries (TAs) of individuals with giant cell arteritis (GCA), the most common systemic vasculitis in older adults. Thus, we explored the contribution of VZV to GCA pathogenesis.

Methods: Formalin-fixed, paraffin-embedded TA sections from biopsy-positive GCA participants with VZV antigen (GCA/VZV-positive; n = 20) and without (GCA/VZV-negative, n = 20) and from normal participants with VZV antigen (control/VZV-positive, n = 11) and without (control/VZV-negative, n = 20) were analyzed by targeted RNA sequencing of the whole human transcriptome (BioSpyder TempO-Seq). Ingenuity pathway analysis and R-computational program were used to identify differentially expressed genes and pathways between groups.

Results: Compared with control/VZV-negative TAs, GCA/VZV-negative and GCA/VZV-positive TAs were significantly enriched for human transcripts specific for pathways involved in viral infections, including viral entry, nuclear factor kappa B activation by viruses, and other pathogen-related immune activation pathways. Similarly, human gene sets supporting viral infection were found in control/VZV-positive TAs that showed no morphological signs of inflammation, suggesting that the enriched pathways were not nonspecific signatures of infiltrating immune cells. All GCA TAs and control/VZV-positive TAs showed enrichment of transcripts involved in vascular remodeling, including smooth muscle cell migration.

Discussion: The detection of viral and immune activation pathways in GCA TAs supports a role for virus infection in GCA pathogenesis. In addition, the detection of viral pathways in control/VZV-positive TAs, along with vascular remodeling pathways, suggests that these samples may represent early infection with progression to clinical disease, depending on host and other environmental factors.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Antigens, Viral / isolation & purification*
  • DNA, Viral / isolation & purification*
  • Female
  • Formaldehyde
  • Gene Expression Profiling
  • Giant Cell Arteritis / pathology
  • Giant Cell Arteritis / virology*
  • Herpesvirus 3, Human*
  • Humans
  • Male
  • Middle Aged
  • Paraffin Embedding
  • Sequence Analysis, RNA
  • Temporal Arteries / pathology
  • Temporal Arteries / virology*
  • Tissue Fixation


  • Antigens, Viral
  • DNA, Viral
  • Formaldehyde