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Human herpes simplex viruses in benign and malignant thyroid tumours
Kirk Jensen1, Aneeta Patel, Alexander Larin
1Department of Pediatrics, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, USA.
The Journal of Pathology
|May 11, 2010
Summary
Herpes simplex virus (HSV) DNA is frequently found in thyroid tumors. Increased expression of the HSV entry receptor nectin-1 and activated signaling pathways enhance thyroid cancer cell susceptibility to HSV during tumor progression.
Area of Science:
- Oncology
- Virology
- Molecular Biology
Background:
- Thyroid neoplasia is a significant health concern.
- The potential role of viral infections, specifically herpes viruses, in thyroid cancer development remains under investigation.
Purpose of the Study:
- To investigate the presence and role of herpes simplex virus 1 (HSV1) and herpes simplex virus 2 (HSV2) in benign and malignant thyroid lesions.
- To explore the molecular mechanisms underlying thyroid cancer cell susceptibility to HSV.
Main Methods:
- Analysis of thyroid tissues for HSV1 and HSV2 DNA using PCR and sequencing.
- Examination of viral gene expression, viral-inducible signaling pathways (e.g., interferon-beta, NFkappaB), and lymphocyte infiltration.
- Assessment of the viral entry receptor nectin-1 expression in patient samples and thyroid cancer cell lines.
- In vitro experiments to determine the impact of signaling pathways on HSV susceptibility.
Main Results:
- HSV DNA was detected in 39.4% of examined thyroid samples.
- HSV capsid protein expression correlated with HSV DNA presence.
- HSV-positive tumors showed activated virus-inducible signaling, lymphocyte infiltration, and oncocytic features.
- HSV2 was significantly associated with papillary thyroid cancer and lymph node metastasis.
- Nectin-1 expression was upregulated in thyroid tumors, particularly papillary thyroid cancer, and correlated with HSV susceptibility in cancer cell lines.
- Inhibition of PI3K/AKT or MAPK/ERK signaling reduced but did not eliminate HSV susceptibility.
Conclusions:
- Herpes simplex virus is frequently detected in thyroid cancer.
- Thyroid tumor progression involves increased susceptibility to HSV, mediated by elevated nectin-1 expression and activated mitogenic signaling pathways in cancer cells.
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