Infection and persistence of erythrovirus B19 in benign and cancerous thyroid tissues.

Human erythrovirus B19 (EVB19) is a small, pathogenic DNA virus that has been associated with a wide range of illnesses. The primary site of replication is in bone marrow-derived erythroid progenitor cells, but EVB19 DNA has been detected in a wide range of organs. Recently, studies have linked EVB19 to thyroid cancers and other thyroid diseases. Previous studies from multiple laboratories have detected EVB19 capsid proteins in Graves' disease, Hashimoto's thyroiditis, and thyroid cancer tissues. Data on viral gene expression and mechanism of infection in the thyroid are lacking. To investigate EVB19 infection and persistence in the thyroid, previously archived adult and pediatric tissue sections were examined for EVB19 DNA, RNA, and capsid proteins, as well as EVB19 receptor P-antigen and co-receptor α5ß1 integrin. EVB19 DNA and protein were detected in a majority of tissues examined (87% and 68%, respectively). Detection was similar in adult and pediatric samples. Quantification of viral genomes revealed no significant difference in the amount of viral DNA in benign, cancerous, or metastatic thyroid tissues. EVB19 capsid RNA was detected in 67% of the tissues examined, confirming at least low-level viral gene expression. Immunohistochemical staining for P-antigen and α5ß1 detected the receptor and co-receptor most frequently on normal thyroid epithelial cells. EVB19 capsid staining could be detected in tumors lacking viral receptors. These results suggest that normal thyroid epithelial cells are the initial target for EVB19 infection in the thyroid and allow for continued persistence in both normal and cancerous thyroid tissues.

Increased IL-6 detection in adult and pediatric lymphoid tissue harboring parvovirus B19.

BACKGROUND: Parvovirus B19 (B19V) is a common pathogenic virus infecting humans. Previous studies have shown evidence of B19V infection in patients with non-Hodgkin's lymphoma (NHL) and Hodgkin's lymphoma using ELISA and PCR on serum specimens. B19V nonstructural protein is known to alter the expression of cellular factors including interleukin-6 (IL-6), which can increase the risk for and worsen the prognosis of lymphomas. OBJECTIVE: The objective of this study was to detect B19V capsid protein and IL-6 expression in normal and malignant lymphoid tissue, as well as any correlation between the two. STUDY DESIGN: IHCs for B19V capsid protein, IL-6, and B19V co-receptors P-antigen and α5ß1 integrin were performed on a tissue array containing 70 duplicated pediatric and adult lymphoma tissues and 5 duplicated benign lymph node sections. Cases were identified as normal, B-cell NHL, diffuse large B-cell NHL, Hodgkin's lymphoma, extranodal NK/T cell lymphoma, anaplastic large cell lymphoma, or mantle cell lymphoma. IL-6 and B19V capsid staining were quantified using a positive pixel count algorithm, and P-antigen and α5ß1 staining using a membrane quantification algorithm. RESULTS: B19V capsid protein was detected in both benign and malignant lymphoid tissue. The Spearman rank correlation coefficient analysis was performed to determine the relationship between the level of positivity for B19V and IL-6 staining, yielding an overall correlation coefficient of 0.679 (p-value<0.0001). CONCLUSIONS: Our results show a moderate correlation between the levels of positive B19V and IL-6 staining by IHC, indicating a possible role for B19V in the pathogenesis of lymphomas.

Detection of parvovirus B19 capsid proteins in testicular tissues.

OBJECTIVE: To detect B19 capsid proteins, VP1 and VP2, in testicular tissues, both normal and tumor, using immunohistochemistry. METHODS: Samples of normal, fetal, and tumor testicular tissue (n = 31) and normal testicular DNA (n = 1) were tested for the presence of B19. Immunohistochemistry staining was used for the detection of viral capsid proteins VP1 and VP2. Polymerase chain reaction with 4 primer sets was used to test for the presence of B19 DNA in a normal testicular sample. RESULTS: B19 capsid protein VP1 and VP2 was detected by immunohistochemistry in 6 (85.7%) of 7 normal testicular samples and 17 (73.9%) of 23 tumor samples. The findings from a normal fetal testicular sample were equivocal. B19 DNA was detected in normal testicular DNA with 4 of the 4 primer sets used. CONCLUSION: In contrast to previous reports, B19 capsid proteins VP1 and VP2 have now been detected in both normal and tumor testicular tissue. The persistence of B19 in a diverse range of tissues, including the testes, requires more research into the molecular mechanisms by which B19 can enter these cells, as well as the possible etiologic roles in chronic diseases, including cancer.

Parvovirus B19 infection in Hashimoto's thyroiditis, papillary thyroid carcinoma, and anaplastic thyroid carcinoma.

BACKGROUND: The human pathogenic parvovirus B19 (B19) has recently been detected in papillary thyroid carcinoma (PTC) and Hashimoto's thyroiditis (HT) tissues at a high frequency in two studies of a Chinese cohort. We wanted to extend these data to include another cohort and expand the thyroid tumor tissue types assessed. In particular, we were interested to find whether B19 also infects anaplastic thyroid carcinoma (ATC), one of the most aggressive human cancers. METHODS: Commercially available thyroid tumor tissue arrays were used to detect B19 capsid protein by immunohistochemistry in various types of thyroid tumors and disorders. The arrays were representative of the four main types of thyroid tumors, as well as other thyroid autoimmune disorders such as HT and Graves' disease, and adenomas, goiters, lymphomas, and normal thyroid tissue. In total, at least 12 different types of thyroid conditions as well as normal tissue were represented, many with multiple subjects. RESULTS: Twenty-one of the 24 (88%) PTC tumors, 3 of the 3 ATC/undifferentiated tumors, and 3 of the 3 HT tissue samples were positive for B19 capsid protein by immunohistochemistry. The localization of the protein differed based on pathological disease type, with a nuclear to cytoplasmic shift seen from unaffected to tumor tissue. CONCLUSIONS: We extend the data available on B19 detection in the thyroid to show a high correlation of virus in another cohort of PTC and HT at the protein level. We also show, for the first time, B19 infection of much more highly aggressive ATC/undifferentiated tumors. Nuclear to cytoplasmic shift in B19 protein in cancer tissue suggests a possible link between B19 and thyroid cancer pathogenesis/progression.