Evidence for possible role of toll-like receptor 3 mediating virus-induced progression of pituitary adenomas

• HPV16 and HHV6B infection rate are higher in invasive human pituitary adenoma(PA) samples.
• Toll-like receptor 3 expresses highly in invasive human PA samples.
• Activation of the TLR3 by viral mimic Poly(I:C) enhances proliferation, survival and invasion of GH3 PA cell line.
• Activation of NF-κB and downstream cytokines may involve in the process.

Tumor-related viruses are known to be involved in initiation and progression of certain tumors. However, the relationship between virus and pituitary adenomas (PAs) remains unknown. Here, we investigated infection status of three types of viruses (HPV16, HHV6B and HSV1) and expression level of toll-like receptor 3 (TLR3) in 60 human PA samples. We also determined the role of TLR3 signaling pathway on a PA cell line (GH3). We firstly found that positive rates of HPV16 and HHV6B infection were significantly higher in invasive PA samples than in noninvasive samples (P < 0.01). Similarly, TLR3 mRNA and protein expression also increased in invasive PA samples (P < 0.01). In vitro analysis indicated that GH3 cell proliferation and survival were enhanced by TLR3 activation, which was accompanied by NF-κB activation. Our data indicate that HPV16 and HHV6B viruses may be involved in promoting the progression of PA by activating the TLR3 signaling pathway.