Reactivation of Human Herpesvirus 6 (HHV-6) in Diverticulitis

Background: Diverticular disease is a significant healthcare burden in the United States. Younger diverticulitis patients are at increased risk for recurrence. How the molecular pathophysiology differs from those that develop disease at an older age is not understood. We aimed to profile the colonic transcriptome from younger versus older diverticulitis patients to identify differential biological pathways contributing to disease. Methods: We performed RNA-seq on full-thickness sigmoid colon tissue obtained at the time of surgery on diverticulitis patients (n=26) diagnosed at a younger age (<42 years old) or at an older age (>65 years old). Viral reads were identified from the RNA-seq dataset and associated with clinical metadata and the host transcriptome. HHV-6 positivity was evaluated in diverticulitis patients by PCR and immunofluorescence. Patient sera was profiled for HHV-6 using qPCR and ELISA to detect anti-HHV-6 antibodies. Results: Using RNA-seq, diverticulitis patients were profiled for differential expression associated with age of diagnosis. A subset of younger diverticulitis patients (diverticulitis colonic transcriptome-viral signature (DCT-VS)) demonstrated increased expression of anti-viral response genes. We identified viral transcripts in the RNA-seq dataset and found HHV-6 transcripts negatively correlated with DCT-VS. Younger patients more frequently displayed evidence of HHV-6 infection through DNA analysis and immunofluorescence of colonic tissue. During acute disease, HHV-6 DNA was detected in the serum but was absent during disease quiescence. Conclusions: Patients diagnosed with diverticulitis at a younger age demonstrate reactivation of HHV-6 in the sigmoid colon that remains persistent. Future studies to assess the role of pathogenicity and the use of anti-virals for acute uncomplicated diverticulitis should be considered. Overall design: Examination of full-thickness sigmoid colon tissue from 26 diverticulitis patients, including 13 diagnosed at an younger age (<42 years old) and 13 diagnosed at an older age (>65 years old)

26

Schieffer KM, Kline BP, Harris LR, Deiling S, Koltun WA, Yochum GS