Research fellow Massachusetts Gen. Hosp., Harvard Med. Sch. Charlestown, Massachusetts, United States
Disclosure(s):
YUN XIA, PhD: No financial relationships to disclose
Introduction/Rationale: Polyomaviruses are small double-stranded DNA viruses and can persist at low levels in the host, typically without causing symptoms in immunocompetent individuals. Emerging data have revealed the beneficial function of the human commensal virome in suppressing cancer and infectious diseases. Herein, we examined the role of polyomaviruses in modulating the immune response to inflammatory stimuli, offering valuable insights into autoimmune disease mechanisms and potential therapeutic approaches.
Methods: To assess the role of polyomaviruses in inflammation, we first infected mouse and human fibroblasts with mouse polyomavirus (MPyV) and human polyomavirus (HPyV), respectively, and then stimulated them with type I interferon-inducing agents. To investigate the role of MPyV in lupus development, MRL/LPR lupus-prone mice were colonized with MPyV and subsequently exposed to UV radiation to accelerate lupus onset. For human studies, facial skin lesion samples from lupus patients and healthy controls were used to detect and quantify HPyVs.
Results: Polyomavirus colonization did not significantly increase the expression of interferon-stimulated genes (ISGs) in fibroblasts. In contrast, polyomavirus markedly reduced interferon responses following stimulation with several agonists. MPyV colonization dramatically reduced systemic lupus phenotype in MRL/LPR mice, including decreased skin lesions, reduced epidermal thickness, and diminished skin immune cell infiltration. Additionally, MPyV-treated mice showed lower serum anti-dsDNA antibody levels and reduced proteinuria. Complement and immune complex deposition in the kidneys were also markedly diminished in MPyV-colonized mice. Lupus patients’ lesional skin exhibited reduced HPyV6 DNA level relative to normal skin.
Conclusion: This research demonstrates that commensal polyomavirus infection suppresses inflammation in the colonized organs. Our findings suggest that commensal polyomaviruses modulate host innate immune responses and mitigate inflammatory diseases.
