In patients infected with the hepatitis C virus (HCV), 20% to 30% will progress to cirrhosis in over two to three decades. Viral and host factors that are important in the clinical and histologic progression of HCV infection are not entirely certain. It has been suggested that liver disease is worse in alcoholics infected with HCV. In the present retrospective study, we examined the effect of moderate alcohol intake on the histologic and clinical progression of HCV infection and assessed whether other variables such as gender, length of exposure, mode of exposure, HCV RNA levels, and ferritin levels also independently impacted disease progression. Liver biopsies were analyzed for the degree of fibrosis, presence of cirrhosis, and histologic activity by using the Histologic Activity Index of Knodell. Patients were divided into two groups based on whether their alcohol intake was significant or not significant. Significant alcohol intake was defined as G40 g alcohol/day in women and G60 g of alcohol/day in men for G5 years. Groups were further divided based on the decades of exposure to HCV. There was no difference in the age or length of exposure to HCV in the alcohol and the alcoholfree group. HCV RNA serum levels, ferritin levels, and viral genotypes were similar in both groups. There was a two-to threefold greater risk of liver cirrhosis and decompensated liver disease in the alcohol group. Also, the rate to which subjects developed cirrhosis was faster in the alcohol group with 58% being cirrhotic by the second decade as opposed to 10% being cirrhotic in the nonalcohol group by the second decade. The histologic and clinical acceleration of liver disease was independent of the mode of exposure or sex. In summary, alcohol intake is an independent risk factor in the clinical and histologic progression of HCV infection. (HEPATOLOGY 1998;28:805-809.)In the United States 3 to 4 million people are infected with HCV. HCV infection is an indolent disease with patients rarely having clinical symptoms until cirrhosis develops. Ten to thirty percent of patients infected with HCV will develop cirrhosis over a 20 to 30 year period, and 1% to 5% will develop hepatocellular carcinoma. [1][2][3][4] Host and viral factors that are important in enhancing the progression to cirrhosis are not entirely clear. 5 Proposed contributory factors include viral genotype, circulating viral load, duration of infection, mode of infection, iron load, gender, and alcohol consumption. [1][2][3][4][5] It is recognized that 5% to 25% of chronic alcoholics with liver disease have a positive HCV antibody test. 6-12 Also, a number of studies have suggested that patients with alcoholic liver disease who are infected with the HCV have more impaired biochemical function and a greater chance of developing cirrhosis. [6][7][8][9][10][11][12] Alcohol intake has also been implicated as an independent risk factor in the progression of HCV, 13 although its overall effect on both the histologic and clinical progression of liver disease in patients chronicall...

Many SARS CoV-2 serology tests have proven to be less accurate than expected and do not assess antibody function as neutralizing, correlating with protection from reinfection. A new assay technology measuring the interaction of purified SARS CoV-2 spike protein receptor binding domain (RBD) with the extracellular domain of the human ACE2 receptor detects these important antibodies. This cPassTM surrogate virus neutralization test (sVNT) when compared directly with eight SARS CoV-2 IgG serology and two live cell neutralization tests gives similar or improved accuracy for qualitative delineation between positive and negative individuals in a fast, scalable and high throughput assay. The combined data support cPassTM sVNT as a tool for highly accurate SARS CoV-2 immunity surveillance of infected/recovered and/or vaccinated individuals, as well as drug and convalescent donor screening. The data also prevue a novel application for cPassTM sVNT in calibrating the stringency of live cell neutralization tests and its use in longitudinal testing of recovered and/or vaccinated patients.

During viral infection, proper regulation of immune responses is necessary to ensure successful viral clearance with minimal host tissue damage. Proteasomes play a crucial role in the generation of antigenic peptides for presentation on MHC class I molecules, and thus activation of CD8 T cells, as well as activation of the NF-κB pathway. A specialized type of proteasome called the immunoproteasome is constitutively expressed in hematopoietic cells and induced in non-immune cells during viral infection by interferon signaling. The immunoproteasome regulates CD8 T cell responses to many viral epitopes during infection. Accumulating evidence suggests that the immunoproteasome may also contribute to regulation of proinflammatory cytokine production, activation of the NF-κB pathway, and management of oxidative stress. Many viruses have mechanisms of interfering with immunoproteasome function, including prevention of transcriptional upregulation of immunoproteasome components as well as direct interaction of viral proteins with immunoproteasome subunits. A better understanding of the role of the immunoproteasome in different cell types, tissues, and hosts has the potential to improve vaccine design and facilitate the development of effective treatment strategies for viral infections.

Lymph node (LN) expansion during an immune response is a complex process that involves the relaxation of the fibroblastic network, germinal center formation, and lymphatic vessel growth. These processes require the stromal cell network of the LN to act deliberately to accommodate the influx of immune cells to the LN. The molecular drivers of these processes are not well understood. Therefore, we asked whether the immediate cytokines type 1 IFN produced during viral infection influence the lymphatic network of the LN in mice. We found that following an IFN-inducing stimulus such as viral infection or polyI:C, programmed cell death ligand 1 (PD-L1) expression is dynamically upregulated on lymphatic endothelial cells (LECs). We found that reception of type 1 IFN by LECs is important for the upregulation of PD-L1 of mouse and human LECs and the inhibition of LEC expansion in the LN. Expression of PD-L1 by LECs is also important for the regulation of LN expansion and contraction after an IFN-inducing stimulus. We demonstrate a direct role for both type 1 IFN and PD-L1 in inhibiting LEC division and in promoting LEC survival. Together, these data reveal a novel mechanism for the coordination of type 1 IFN and PD-L1 in manipulating LEC expansion and survival during an inflammatory immune response.