TAILIEUCHUNG - Báo cáo y học: " Herpes simplex virus UL56 interacts with and regulates the Nedd4-family ubiquitin ligase Itch"

Herpes simplex virus UL56 interacts with and regulates the Nedd4-family ubiquitin ligase Itch | Ushijima et al. Virology Journal 2010 7 179 http content 7 1 179 VIROLOGY JOURNAL RESEARCH Open Access Herpes simplex virus UL56 interacts with and regulates the Nedd4-family ubiquitin ligase Itch Yoko Ushijima Chenhong Luo Maki Kamakura Fumi Goshima Hiroshi Kimura Yukihiro Nishiyama Abstract Background Herpes simplex virus type 2 HSV-2 is one of many viruses that exploits and modifies the cellular ubiquitin system. HSV-2 expresses the tegument protein UL56 that has been implicated in cytoplasmic transport and or release of virions and is a putative regulatory protein of Nedd4 ubiquitin ligase. In order to elucidate the biological function of UL56 this study examined the interaction of UL56 with the Nedd4-family ubiquitin ligase Itch and its role in the regulation of Itch. Additionally we assessed the similarity between UL56 and regulatory proteins of Itch and Nedd4 Nedd4-family-interactins proteins Ndfip . Results UL56 interacted with Itch independent of additional viral proteins and mediated more striking degradation of Itch compared to Nedd4. Moreover it was suggested that the lysosome pathway as well as the proteasome pathway was involved in the degradation of Itch. Other HSV-2 proteins with PY motifs such as VP5 and VP16 did not mediate the degradation of endogenous Itch. Ndfip1 and Ndfip2 were similar in subcellular distribution patterns to UL56 and colocalized with UL56 in co-transfected cells. Conclusions We believe that this is the first report demonstrating the interaction of a HSV-specific protein and Itch. Thus UL56 could function as a regulatory protein of Itch. The mechanism function and significance of regulating Itch in HSV-2 infection remain unclear and warrant further investigation. Background Viruses act as intracellular parasites depending heavily on functions provided by their host cells and have evolved diverse strategies to exploit the biology and biochemistry of hosts for their benefit 1 . The ubiquitin system is one of the

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