Hepatocellular Carcinoma with Direct Invasion to the Duodenal Bulb, Presenting with Gastrointestinal Bleeding

Hemorrhage from hepatocellular carcinoma (HCC) directly invading the gastrointestinal tract is very rare. A 71-yearold man, who had been treated with transcatheter arterial embolization and percutaneous ethanol injection for HCC in the right hepatic lobe, presented with melena. Endoscopic examination showed a crater-like ulceration coated with blood clot in the duodenal bulb, and microscopic examination of a biopsy specimen from the duodenal lesion confirmed HCC. Abdominal computed tomography (CT) revealed that the HCC mass containing air-density invaded the duodenum. Recurrent bleeding continued from the lesion and the patient died of liver failure. Postmortem examination revealed massive HCC with hepatoduodenal fistula caused by direct tumor invasion into the duodenum

A screen of FDA-approved drugs with minigenome identified tigecycline as an antiviral targeting nucleoprotein of CrimeanCongo hemorrhagic fever virus

Crimean-Congo hemorrhagic fever virus (CCHFV) belongs to the genus Orthonairovirus and is the causative agent of a viral hemorrhagic disease with a case fatality rate of 30%. However, limited studies have been conducted to explore antiviral compounds specific to CCHFV. In this study, we developed a minigenome system of orthonairoviruses, CCHFV and Hazara virus to analyze viral replication and screened an FDA-approved compound library. The transfection of the minigenome components induced marked increase in luciferase expression, indicating the sufficient replication and translation of reporter RNA. Compound library screening identified 14 candidate compounds that significantly decreased luciferase activity. Some of the compounds also inhibited the replication of the infectious Hazara virus. The mechanism of inhibition by tigecycline was further analyzed, and a decrease in the interaction between the viral N protein and RNA by tigecycline was observed. This work provides a basis for validation using animal models and the design of chemical derivatives with stronger activity in future studies on the development of an antiviral against CCHFV

BST-2 controls T cell proliferation and exhaustion by shaping the early distribution of a persistent viral infection

The interferon inducible protein, BST-2 (or, tetherin), plays an important role in the innate antiviral defense system by inhibiting the release of many enveloped viruses. Consequently, viruses have evolved strategies to counteract the anti-viral activity of this protein. While the mechanisms by which BST-2 prevents viral dissemination have been defined, less is known about how this protein shapes the early viral distribution and immunological defense against pathogens during the establishment of persistence. Using the lymphocytic choriomeningitis virus (LCMV) model of infection, we sought insights into how the in vitro antiviral activity of this protein compared to the immunological defense mounted in vivo. We observed that BST-2 modestly reduced production of virion particles from cultured cells, which was associated with the ability of BST-2 to interfere with the virus budding process mediated by the LCMV Z protein. Moreover, LCMV does not encode a BST-2 antagonist, and viral propagation was not significantly restricted in cells that constitutively expressed BST-2. In contrast to this very modest effect in cultured cells, BST-2 played a crucial role in controlling LCMV in vivo. In BST-2 deficient mice, a persistent strain of LCMV was no longer confined to the splenic marginal zone at early times post-infection, which resulted in an altered distribution of LCMV-specific T cells, reduced T cell proliferation / function, delayed viral control in the serum, and persistence in the brain. These data demonstrate that BST-2 is important in shaping the anatomical distribution and adaptive immune response against a persistent viral infection in vivo

BST-2 deficiency changes the splenic distribution and proliferative capacity of antiviral CD8+ T cells.

<p><b>A.</b> Representative confocal images were captured at day 4 post-infection in the spleens of WT and BST-2 KO mice seeded with mOrange+ P14 cells (green). The splenic distribution of P14 cells in relation to LCMV Cl-13 (red) is shown. The white dotted line demarcates the border between the white pulp (WP) and red pulp (RP). <b>B.</b> The bar graph shows quantification of the white vs. red pulp P14 percentage in WT vs. BST-2 KO mice (n = 4 mice per group; 2 independent experiments). Data are represented as mean ± SD. Asterisks denote statistical significance (*P < 0.05). <b>C.</b> The representative histogram depicts the dilution of CFSE in P14 cells from WT (blue) vs. BST-2 KO (red) mice at day 3 post-infection. <b>D.</b> The bar graph shows quantification of the CFSE dilution data in panel C (n = 4 mice per group; 2 independent experiments). Graphed are the percentage of P14 cells that divided more than 5 times. Data are represented as mean ± SD. Asterisks denote statistical significance (*P ≤ 0.05).</p