Hepatitis delta virus detected in Sjögren’s syndrome salivary gland tissue.

Objectives: Persistent, low-level viral infections have been suspected as a trigger in the development of primary Sjögren’s syndrome (pSS). While prior studies have detected the presence of viruses in salivary glands of pSS patients, a clear cause-and-effect relationship has been difficult to establish. Therefore, a study was designed to globally identify potential viral signatures in the pathogenesis of Sjögren’s syndrome and to evaluate the capacity of identified virus(es) to recapitulate the disease phenotype in vivo.
Methods: A custom viral microarray was designed to identify low-level transcripts from actively replicating viruses present within salivary gland tissue of 15 pSS patients compared to 14 healthy controls. Presence of hepatitis delta virus (HDV) was confirmed by RT-PCR and immunodetection of HDV antigens. HDV antigens were expressed in salivary glands of female C57BL/6 mice using adeno-associated viral (AAV) vectors and were monitored for changes in stimulated saliva flow, lymphocytic infiltrate formation and development of autoantibodies.
Results: Hepatitis delta virus (HDV) was detected in 50% of the pSS patients compared to healthy controls. Presence of HDV sequence and antigens were confirmed in initial cohort, a secondary cohort and by an independent lab. Patients testing positive for HDV in salivary gland tissue lacked evidence of a past or current HBV co-infection. Transaminase levels were within normal range suggesting absence of active hepatitis. In vivo expression of HDV antigens in murine salivary glands resulted in the reduction of stimulated saliva flow, development of autoantibodies and increased lymphocytic focal infiltrates.
Conclusions: This study identified the presence of HDV in affected salivary gland tissue from pSS patients and capacity of HDV antigens to trigger a pSS-like phenotype in vivo. Detection of HDV in the absence of HBV points to a unique tissue tropism and/or mechanism of persistence not previously identified for HDV.