Structure and sequence of the saimiriine herpesvirus 1 genome

We report here the complete genome sequence of the squirrel monkey α-herpesvirus saimiriine herpesvirus 1 (HVS1). Unlike the simplexviruses of other primate species, only the unique short region of the HVS1 genome is bounded by inverted repeats. While all Old World simian simplexviruses characterized to date lack the herpes simplex virus RL1 (γ34.5) gene, HVS1 has an RL1 gene. HVS1 lacks several genes that are present in other primate simplexviruses (US8.5, US10-12, UL43/43.5 and UL49A). Although the overall genome structure appears more like that of varicelloviruses, the encoded HVS1 proteins are most closely related to homologous proteins of the primate simplexviruses. Phylogenetic analyses confirm that HVS1 is a simplexvirus. Limited comparison of two HVS1 strains revealed a very low degree of sequence variation more typical of varicelloviruses. HVS1 is thus unique among the primate α-herpesviruses in that its genome has properties of both simplexviruses and varicelloviruses.     

Proteinase-activated receptors 1 and 2 regulate invasive behavior of human melanoma cells via activation of protein kinase D1

Recent studies have indicated an important role of proteinases and proteinase-activated receptors (PARs) in tumorigenesis. Although a role for PARs has been described in various skin tumors including melanoma, the underlying cellular mechanisms have not been understood. Recent studies have suggested PAR(1) as a regulator of melanoma cell growth and metastasis by affecting angiogenic and invasive factors. Moreover, changes in the expression patterns of PAR(1) and PAR(2) correlate with skin cancer progression, and PAR(1) is overexpressed in melanoma. Therefore, we sought to elucidate the putative role of PAR(1)- and PAR(2)-mediated signal transduction pathways during melanoma progression. Activation of both PAR(1) and PAR(2) led to rapid phosphorylation of protein kinase D1 (PKD1) in cultured WM9 melanoma cells. PKD1 is known to be involved in cell migration, integrin regulation, and intracellular vesicle transport. Downregulation of PKD1 by siRNA resulted in diminished proliferation, decreased αvβ3 integrin regulation, and secretion of pro-angiogenic chemokine IL-8 in WM9 cells. In conclusion, our results show that PAR(1) and PAR(2) are involved in WM9 cell proliferation and secretion of IL-8 by activation of PKD1. Inactivation of the PKD1 pathway may be beneficial for the inhibition of PAR-induced melanoma proliferation and for maintenance of the inflammatory tumor environment.     

Hb Southampton [beta106(G8)Leu-->Pro, CTG-->CCG] in an Argentinean boy

Hb Southampton (also known as Hb Casper) is characterized by the substitution of a leucine residue for a proline at codon beta106 (CTG-->CCG). This mutation breaks the G helix and severely distorts the tertiary structure of the molecule, producing an unstable hemoglobin (Hb) and severe hemolysis. We identified this hemoglobinopathy in a young patient with severe hemolytic anemia and hepatosplenomegaly.