Hiasa, Y. | bioRxiv Science

bioRxiv2022

HBs-S antigen-dependent enhancement of HBV infection

Background AimsIn natural infections with hepatitis B virus (HBV), large amounts of hepatitis B surface-small antigen (HBs-S) subviral particles (SVPs), which do not contain viral nucleocapsid, are secreted into the blood. The function of excess amounts of SVPs remains largely unknown. In this study, we analyzed the function of HBs-S in HBV infection. MethodsThe effect of HBs-S in HBV infection was evaluated in a human hepatoma cell line, in primary human hepatocytes, and in chimeric mice with humanized livers. To analyze the involvement of glycosaminoglycan, HBs-S attachment to cells in the presence of heparin was evaluated by enzyme-linked immunosorbent assay (ELISA), and the enhancement of viral attachment was evaluated by measurement of viral DNA. Additionally, the interaction between HBs-S and viral particles was analyzed by immunoprecipitation. ResultsAttachment of the HBV DNA to cells inoculated with the combination of virus and HBs-S was significantly higher than that to cells inoculated with HBV only. Pretreatment of the cells with HBs-S also increased viral DNA levels significantly compared to that in untreated cells. In contrast, HBs-L did not enhance the viral attachment. Enhancement of viral attachment was associated with the attachment of HBs-S to the cells via heparan sulfate. HBs-S also interacted with the viral particle. Furthermore, in chimeric mice with humanized livers, HBs-S enhanced HBV infection. ConclusionsWe demonstrated that HBs-S enhances viral attachment in vitro and viral infection in vivo. HBs-S interacted with heparan sulfate on the cellular surface, and this interaction contributed to the enhancement of viral attachment. These data indicate that HBs-S enhances the viral infection, and may contribute to the high transmissibility of HBV.

microbiology↗

bioRxiv2021

Translation of cellular protein localization by generative adversarial network

The protein localization in cells had been analyzed by the fluorescent labeling by indirect immunofluorescence and fluorescent protein tagging. However, the relationships between the localizations between different proteins had not been analyzed by artificial intelligence. In this study, we applied the generative adversarial network (GAN) to generate the protein localizations each other, in which the generation was dependent on the types of cells and the relationships between the proteins. Lamellipodia are one of the actin-dependent subcellular structures involved in cell migration and are mainly generated by the Wiskott-Aldrich syndrome protein (WASP)-family verprolin homologous protein 2 (WAVE2) and the membrane remodeling I-BAR domain protein IRSp53. Focal adhesions are another actin-based structure that contains vinculin protein and are essential for cell migration. In contrast, microtubules are not thought to be directly related to actin filaments. The GAN was trained using images of actin filaments paired with WAVE2, vinculin, IRSp53, and microtubules. Then, the generated images of WAVE2, vinculin, and IRSp53 by the GAN showed high similarity to the real images of WAVE2, vinculin, and IRSp53, respectively. However, the microtubule images generated from actin filament images were inferior, corroborating that the microscopic images of actin filaments provide more information about actin-related protein localization. Collectively, this study suggests that the image translation by the GAN can predict the localization of functionally related proteins.

cell biology↗