No abstract

It was reported previously food-borne transmission of hepatitis E virus (HEV) to humans from deer meat. The present study attempted to clarify whether eating uncooked deer meat is a major epidemiological risk factor for HEV infection in Kasai, a city in western Japan. In total, 45 volunteer subjects with experience of eating raw deer meat were enrolled. An equivalent number of people from the same area who had never eaten raw deer meat served as controls. The subjects and controls had comparable age and sex distributions. Serum anti-HEV IgG and anti-hepatitis A virus (HAV) IgG levels were measured in all 90 volunteers. There was no significant difference in age, overseas travel history, or rate of anti-HAV antibody positivity between the subjects and controls. Eight (17.7%) of the subjects but only one (2.2%) of the controls had measurable serum anti-HEV IgG levels (P = 0.014). Anti-HAV prevalence did not differ between the anti-HEV-positive and negative groups. The results suggest that eating uncooked deer meat is an epidemiological risk factor for HEV infection in the studied area. In countries such as Japan where deer meat is sometimes eaten raw, attention must be paid to this route of HEV infection.

Retinoblastoma protein (RB) acts as a tumor suppressor in many tissue types, by promoting cell arrest via E2F-mediated transcriptional repression. In addition to the aberrant forms of the RB gene found in different types of cancers, many viral oncoproteins including the simian virus 40 large T antigen target RB. However, cellular factors that inhibit RB function remain to be elucidated. Here, we report that RB interacts with the high mobility group protein A1 (HMGA1), a-non-histone architectural chromatin factor that is frequently overexpressed in cancer cells. HMGA1 binds the small pocket domain of RB, and competes with HDAC1. Subsequently, overexpression of HMGA1 abolishes the inhibitory effect of RB on E2F-activated transcription from the cyclin E promoter. Under serum starvation, T98G cells had been previously shown to be arrested in the G0 phase in an RB-mediated manner. The G0 phase was characterized by growth arrest and low levels of transcription, together with the hypophosphorylation of RB and the downregulation of HMGA1. In contrast, such serum-depleted G0 arrest was abrogated in T98G cells overexpressing HMGA1. T he retinoblastoma protein (RB) is known to be a key regulator of cell proliferation and arrest, and is therefore implicated in tumor suppression and cell differentiation.(1-4)The principal role of RB is in the control of the cell cycle by repressing the E2F family of transcription factors, which regulate the expression of a number of genes involved in DNA synthesis and cell cycle progression.(5,6) RB suppresses the E2F-mediated transcription of genes in the G1 to the S phase by at least two mechanisms. First, RB binds to the transcriptional activation domain of E2F, and blocks its ability to stimulate gene expression.(6) Second, the formation of the RB-E2F complex results in active repression by recruiting appropriate co-repressors that remodel chromatin to be transcriptionally inactive in the promoter region of E2F-targeted genes. These co-repressors include histone deacetylases (HDACs), (7)(8)(9)(10) histone methyltransferases, (11,12) and DNA methyltransferases. (13,14) RB also influences the accessibility of chromatin through the recruitment of ATP-dependent chromatin remodeling factors such as Brahma (BRM) and BRM-related gene (BRG). (15)(16)(17)(18) Thus, RB plays an important role in epigenetic gene regulation. The ability of RB to repress E2F-mediated transcription highly depends on the phosphorylation of RB by the cyclindependent kinases (cdk), (2,19) indicating that RB itself is governed by cell cycle machineries. In G0 and early G1 phases, RB is primarily unphosphorylated or hypophosphorylated, and becomes phosphorylated in the late G1 to S phase. Phosphorylation gradually increases throughout the S and G2/M phases. The initial phosphorylation occurs in the carboxyl terminal portion of RB by cyclin D/cdk4 and cdk6, and displaces HDACs from the pocket region of RB, (19) leading to the blockade of the repressive role of RB. Subsequently, multiple phosphorylations in the pocket region...

The large T antigens of polyomaviruses target cellular proteins that control fundamental processes, including p53 and the RB family of tumor suppressors. Mechanisms that underlie T-antigen-induced cell transformation need to be fully addressed, because as-yet unidentified target proteins might be involved in the process. In addition, recently identified polyomaviruses are associated with particular human diseases such as aggressive skin cancers. Here, we report that simian virus 40 (SV40) large T antigen interacts with the transforming acidic coiled-coil-containing protein TACC2, which is involved in stabilizing microtubules in mitosis. T antigen directly binds TACC2 and induces microtubule dysfunction, leading to disorganized mitotic spindles, slow progression of mitosis and chromosome missegregation. These mitotic defects are caused by N-terminal-deleted T antigen, which minimally interacts with TACC2, whereas T-antigen-induced microtubule destabilization is suppressed by overexpressing TACC2. Thus, TACC2 might be a key target of T antigen to disrupt microtubule regulation and chromosomal inheritance in the initiation of cell transformation.