A new bunya-like virus associated with mass mortality of white-clawed crayfish in the wild.

We report the discovery of a new enveloped, spherical virus belonging to the Phenuiviridae family of negative ssRNA viruses associated with a massive outbreak in a French population of the endangered white-clawed crayfish Austropotamobius pallipes. We call this virus Bunya-like Brown Spot Virus (BBSV) and characterize it using transmission electronic microscopy, genome sequencing and clinical signs. Infected specimens show discolored brown spots on the cuticle. Using RNA-seq data we assembled a partial sequence for the L, M and S genome segments of BBSV. Phylogenetic analyses using all three segments show this virus is closely related to the Wenling crustacean virus 7 (China) and to a bunya-like virus found in feces of the European otter. Our survey of the mass mortality event indicates the virus is less virulent than the crayfish plague caused by Aphanomyces astaci. Overall, the discovery of BBSV provides a new important asset to monitor A. pallipes populations.

Alterations on the 5' noncoding region of the BCL-6 gene are not correlated with BCL-6 protein expression in T cell non-Hodgkin lymphomas.

The BCL-6 proto-oncogene is expressed in germinal center B lymphocytes, in their neoplastic counterparts, and in a subpopulation of germinal center and perifollicular T lymphocytes. Rearrangements and/or mutations of the 5' noncoding region of the bcl-6 gene have been demonstrated in a large majority of diffuse large B cell lymphomas. Some, but not all, of these genetic alterations lead to dysregulation of the protein. Recently, anaplastic large cell lymphomas with T and null cell phenotypes, as well as T lymphoblastic lymphomas, have also been reported to exhibit immunoreactivity to the anti-BCL-6 antibody. We collected 33 T cell non-Hodgkin lymphomas (T-NHLs) and analyzed their expression of the BCL-6 protein by immunohistochemistry and investigated the organization of the bcl-6 gene by Southern blot and single strand conformation polymorphism (SSCP). The expression of BCL-6 was demonstrated in 37.5% of lymphoblastic (LBL), 40% of anaplastic large cell (ALCL), and 33% of peripheral T cell lymphomas (PTCL). BCL-6-positive malignant cells exhibited the CD4+ or CD4+/CD8+ phenotype. The bcl-6 gene was in a germline configuration in all T-NHLs examined, and a mutation at the first exon-intron boundary region structure of the wild-type bcl-6 gene was detected in 3 of 12 PTCL. One case of PTCL with mutations of the 5' noncoding region expressed BCL-6. In conclusion, expression of the BCL-6 protein is demonstrable independently of bcl-6 alterations in T-NHLs. This further suggests that molecular mechanisms other than rearrangements and/or mutations of the 5' noncoding region of the bcl-6 gene can result in expression of the protein. Whether these lymphomas arose from T cells expressing BCL-6 or expressed BCL-6 as part of the malignant transformation process needs to be determined. Finally, structural alterations of bcl-6 are rare in T-NHLs, but mutations do occur in the 5' noncoding region. We suggest that expression of BCL-6 in T cells may facilitate lymphomagenesis by repressing critical cytokines and cell cycle regulators.

Platelet-derived endothelial cell growth factor/thymidine phosphorylase immunohistochemical expression in lymphoid tissue and lymphoid malignancies.

The catabolic enzyme thymidine phosphorylase (TP) plays a crucial role in nucleic acid metabolism by regulating the availability of thymidine. Platelet-derived endothelial cell growth factor (PD-ECGF) is an angiogenic factor that was recently shown to be TP. The angiogenic properties of PD-ECGF/TP are attributable to a reduction of thymidine levels that results in a promotion of endothelial cell proliferation. Early studies showed a higher concentration of TP in macrophages than in parenchymal cells and in neoplastic than in nonneoplastic tissues. We examined the immunohistochemical expression of PD-ECGF/TP in reactive lymphoid tissues (lymph node and tonsil), as well as in a series of 20 cases of Hodgkin's disease and 31 cases of non-Hodgkin's lymphomas. Macrophages, sinus lining cells, and cells with dendritic morphology, of both follicular dendritic and interdigitating reticular cell type, presented a prominent nuclear and cytoplasmic positivity in reactive lymphoid tissue and in malignant lymphomas. Small lymphocytes and the neoplastic population were always negative, whereas endothelial staining was variable and showed no correlation to the type or grade of the lymphomas. In Hodgkin's disease (with the exception of the nodular lymphocyte predominance type) and some cases of high-grade non-Hodgkin's lymphomas, the positive dendritic cells formed a dense meshwork closely surrounding the neoplastic population. Our results suggest that the reported upregulation of PD-ECGF/TP activity in lymphoid malignancies is attributable to the nonneoplastic population, especially to cells of dendritic morphology.

Localization of alpha 2, alpha 5 and alpha 6 integrin subunits in human endometrium, decidua and trophoblast.

Integrins are heterodimeric glycoproteins acting as membrane receptors for extracellular matrix components. The specificity of these receptors towards one particular matrix glycoprotein depends on the type of alpha and beta subunit combination. Since integrins are involved in the migratory behaviour of cells and since cytotrophoblastic cells are constitutively invasive, we undertook to immunolocalize the alpha 2, alpha 5 and alpha 6 integrin subunits in normal and hydatidiform molar trophoblast, in an implantation site as well as in decidualized and non-decidualized endometrium. alpha 6 positivity was confined to villous cytotrophoblast and was clearly polarized towards the basement membrane. Extravillous cytotrophoblastic cells were alpha 6-negative but became alpha 5-positive. In contrast to normal trophoblast, villous cytotrophoblast from hydatidiform molar tissue was alpha 5-positive. We conclude that the expression of a alpha 5 integrin subunit on cytotrophoblastic cell surfaces is correlated with the appearance of an invasive phenotype. alpha 6 and alpha 2 integrin subunits were both localized on the surface and glandular epithelium of the endometrium and their expression was increased during the secretory phase but became low or undetectable after decidualization. In contrast, alpha 5 subunit positivity was weak in the same epithelial during the first half of the cycle but disappeared after ovulation. Stromal cell alpha 5 positivity was present throughout the cycle but increased dramatically in decidualized endometria. We conclude that the alpha 5 integrin subunit which disappears from the epithelium at the end of the cycle might allow migration of the epithelial cells and repair of the endometrium after menses. We also wonder if alpha 5 positivity is part of a change in the stromal cell phenotype induced by decidualization.