Ribavirin has been used as an antiviral agent for several decades. Although it has activity against numerous viruses, its major use clinically has been in the treatment of respiratory syncytial virus in paediatric patients and chronic HCV infection in both children and adults. This review highlights the clinical application and mechanism of action of ribavirin and discusses the future role of ribavirin in treatment of HCV where there are intense research efforts to improve therapy.

Cell-intrinsic innate immunity provides a rapid first line of defense to thwart invading viral pathogens through the production of antiviral and inflammatory genes. However, the presence of many of these signaling pathways in the liver and their role in hepatitis B virus (HBV) pathogenesis is unknown. Recent identification of intracellular DNA-sensing pathways and involvement in numerous diverse disease processes including viral pathogenesis and carcinogenesis suggest a role for these processes in HBV infection. To characterize HBV-intrinsic innate immune responses and the role of DNA- and RNA-sensing pathways in the liver, we used in vivo and in vitro models including analysis of gene expression in liver biopsies from HBV-infected patients. In addition, mRNA and protein expression were measured in HBV-stimulated and DNA-treated hepatoma cell lines and primary human hepatocytes. In this article, we report that HBV and foreign DNA stimulation results in innate immune responses characterized by the production of inflammatory chemokines in hepatocytes. Analysis of liver biopsies from HBV-infected patients supported a correlation among hepatic expression of specific chemokines. In addition, HBV elicits a much broader range of gene expression alterations. The induction of chemokines, including CXCL10, is mediated by melanoma differentiation–associated gene 5 and NF-κB–dependent pathways after HBV stimulation. In conclusion, HBV-stimulated pathways predominantly activate an inflammatory response that would promote the development of hepatitis. Understanding the mechanism underlying these virus–host interactions may provide new strategies to trigger noncytopathic clearance of covalently closed circular DNA to ultimately cure patients with HBV infection.

Purpose of Review Given the rapid development of diagnostic approaches to test for and diagnose infection with SARS-CoV-2 and its associated variants including Omicron (B.1.1.529), many options are available to diagnose infection. Multiple established diagnostic companies are now providing testing platforms whereas initially, testing was being performed with simple PCR-based tests using standard laboratory reagents. Recent Findings Additional testing platforms continue to be developed, including those to detect specific variants, but challenges with testing, including obtaining testing reagents and other related supplies, are frequently encountered. With time, the testing supply chain has improved, and more established companies are providing materials to support these testing efforts. In the United States (U.S.), the need for rapid assay development and subsequent approval through the attainment of emergency use authorization (EUA) has superseded the traditional arduous diagnostic testing approval workflow mandated by the FDA. Through these efforts, the U.S. has been able to continue to significantly increase its testing capabilities to address this pandemic; however, challenges still remain due to the diversity of the performance characteristics of tests being utilized and newly discovered viral variants. Summary This review provides an overview of the current diagnostic testing landscape, with pertinent information related to SARS-CoV-2 virology, variants and antibody responses that are available to diagnose infection in the U.S.

Chronic infection with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) affects an estimated 35 million and 75 million individuals worldwide, respectively. These viruses induce persistent inflammation which often drives the development or progression of organ-specific diseases and even cancer including Hepatocellular Carcinoma (HCC). In this study, we sought to examine inflammatory responses following HIV or HCV stimulation of macrophages or Kupffer cells (KCs), that may contribute to virus mediated inflammation and subsequent liver disease. KCs are liver-resident macrophages and reports have provided evidence that HIV can stimulate and infect them. In order to characterize HIV-intrinsic innate immune responses that may occur in the liver, we performed microarray analyses on KCs following HIV stimulation. Our data demonstrate that KCs upregulate several innate immune signaling pathways involved in inflammation, myeloid cell maturation, stellate cell activation, and Triggering Receptor Expressed on Myeloid cells 1 (TREM1) signaling. TREM1 is a member of the immunoglobulin superfamily of receptors and it is reported to be involved in systemic inflammatory responses due to its ability to amplify activation of host defense signaling pathways. Our data demonstrate that stimulation of KCs with HIV or HCV induces the upregulation of TREM1. Additionally, HIV viral proteins can upregulate expression of TREM1 mRNA through NF-кB signaling. Furthermore, activation of the TREM1 signaling pathway, with a targeted agonist, increased HIV or HCV-mediated inflammatory responses in macrophages due to enhanced activation of the ERK1/2 signaling cascade. Silencing TREM1 dampened inflammatory immune responses elicited by HIV or HCV stimulation. Finally, HIV and HCV infected patients exhibit higher expression and frequency of TREM1 and CD68 positive cells. Taken together, TREM1 induction by HIV contributes to chronic inflammation in the liver and targeting TREM1 signaling may be a therapeutic option to minimize HIV induced chronic inflammation. Although HIV antiviral therapy has limited the progression to AIDS in infected patients, there is still significant morbidity and mortality from HIV-driven diseases due to sustained inflammation. In this study, we sought to elucidate how HIV and HCV could impact inflammation in the liver and cause progressive liver disease that can eventually lead to cirrhosis and liver cancer. We found that HIV upregulates the inflammatory response amplifier, TREM1, in primary Kupffer Cells (KCs) that are liver-resident macrophages. Enhanced TREM1 expression subsequently is involved in augmented immune responses triggered by HIV or HCV. Additionally, our data demonstrates that blocking TREM1 expression reduces inflammatory responses mediated by HIV or HCV stimulation. Ultimately, our understanding of this mechanism may yield additional therapeutic strategies to help infected patients and give insight into inflammation driven liver cancer.

Plasmacytoid dendritic cells (pDCs) are key components of the innate immune response that are capable of synthesizing and rapidly releasing vast amounts of type I interferons (IFNs), particularly IFN-α. Here we investigated whether pDCs, often regarded as a mere source of IFN, discriminate between various functionally discrete stimuli and to what extent this reflects differences in pDC responses other than IFN-α release. To examine the ability of pDCs to differentially respond to various doses of intact and infectious HIV, hepatitis C virus, and H1N1 influenza virus, whole-genome gene expression analysis, enzyme-linked immunosorbent assays, and flow cytometry were used to investigate pDC responses at the transcriptional, protein, and cellular levels. Our data demonstrate that pDCs respond differentially to various viral stimuli with significant changes in gene expression, including those involved in pDC activation, migration, viral endocytosis, survival, or apoptosis. In some cases, the expression of these genes was induced even at levels comparable to that of IFN-α. Interestingly, we also found that depending on the viral entity and the viral titer used for stimulation, induction of IFN-α gene expression and the actual release of IFN-α are not necessarily temporally coordinated. In addition, our data suggest that high-titer influenza A (H1N1) virus infection can stimulate rapid pDC apoptosis. IMPORTANCE Plasmacytoid dendritic cells (pDCs) are key players in the viral immune response. With the host response to viral infection being dependent on specific virus characteristics, a thorough examination and comparison of pDC responses to various viruses at various titers is beneficial for the field of virology. Our study illustrates that pDC infection with influenza virus, HIV, or hepatitis C virus results in a unique and differential response to each virus. These results have implications for future virology research, vaccine development, and virology as a whole.

Hepatitis C virus (HCV) infections occur in approximately 3% of the world population. The development of an enhanced and extensive-scale screening is required to accomplish the World Health Organization’s (WHO) goal of eliminating HCV as a public health problem by 2030. However, standard testing methods are time-consuming, expensive, and challenging to deploy in remote and underdeveloped areas. Therefore, a cost-effective, rapid, and accurate point-of-care (POC) diagnostic test is needed to properly manage the disease and reduce the economic burden caused by high case numbers. Herein, we present a fully automated reverse-transcription loop-mediated isothermal amplification (RT-LAMP)-based molecular diagnostic set-up for rapid HCV detection. The set-up consists of an automated disposable microfluidic chip, a small surface heater, and a reusable magnetic actuation platform. The microfluidic chip contains multiple chambers in which the plasma sample is processed. The system utilizes SYBR green dye to detect the amplification product with the naked eye. The efficiency of the microfluidic chip was tested with human plasma samples spiked with HCV virions, and the limit of detection observed was 500 virions/mL within 45 min. The entire virus detection process was executed inside a uniquely designed, inexpensive, disposable, and self-driven microfluidic chip with high sensitivity and specificity.