Seroprevalence of segmented flavi-like Alongshan virus in horses.

The emergence of new pathogens poses a significant threat to global health, exacerbated by climate change, biodiversity loss, and increased globalization. Ticks, as vectors for various pathogens, contribute to the rising incidence of diseases. Surveillance programs are crucial for identifying and controlling emerging pathogens.

Ripk1 is critical for preserving effector regulatory T cells and the suppressive transcriptional program in regulatory T cells.

Ripk1 plays an important role as a regulator of programmed cell death processes such as apoptosis and necroptosis and is involved in initiating pro-inflammatory NF-κB signaling. Immune tolerance depends on the proper function and homeostasis of regulatory T (Treg) cells. Here, we show that specific ablation of Ripk1 in Treg cells leads to systemically reduced Treg cell numbers resulting in spontaneous whole-body pathology.

Mycophenolic acid treatment drives the emergence of novel SARS-CoV-2 variants.

Mycophenolic acid (MPA) is commonly used in immunosuppressive regimens following solid organ transplantation. We demonstrate that MPA treatment reproducibly inhibits the replication of a range of viruses, including severe respiratory syndrome coronavirus 2 (SARS-CoV-2). Mechanistically, we identified cellular guanosine triphosphate pool depletion as a key mediator of this antiviral effect.

Interferon-induced immune signatures are associated with suppression of HEV infection in porcine cell culture models.

Hepatitis E virus genotype 3 (HEV-3) is a zoonotic pathogen with pigs representing the natural host. Although HEV-3 infections in humans are often self-limiting, severe or chronic cases can occur. In contrast, HEV-3 infections in pigs, the primary reservoir, remain asymptomatic.

Extrahepatic Replication and Genomic Signatures of the Hepatitis E Virus in the Kidney.

Introduction: The hepatitis E virus (HEV; species Paslahepevirus balayani) is a common human pathogenic and zoonotic virus that can cause both acute fulminant and chronic hepatitis. Despite its reputation as a hepatotropic virus, HEV infection is also associated with a number of extrahepatic diseases, including kidney disorders. However, the extent to which HEV replicates in kidney cells remains unclear.

Disease Burden of RSV Infection in Adult Patients in Comparison to Influenza Virus Infection.

Respiratory Syncytial Virus (RSV) is well known for its impact on children, but its burden in adults remains underexplored, partly due to limited PCR testing before the COVID-19 pandemic. In this study, the medical burden of RSV infections in adults was retrospectively investigated using 6-year longitudinal data from a university hospital in North Rhine-Westphalia, Germany. Outcomes of 380 PCR-confirmed RSV cases were compared with 1088 influenza A/B cases from 2018 to 2023, stratified by age groups ( < 60 and ≥ 60 years).

Virucidal activity of household laundry detergents and additives in simulated wash cycles.

Aims: In this study, we evaluated the antiviral performance of domestic laundry detergents and additives to provide information for selecting a suitable product for reducing viruses on textiles during viral infections at home.

Methods And Results: Three laundry heavy-duty detergents (HDDs)-universal solid, regular liquid, and compact single-dose liquid-and a laundry additive (hygiene rinser) were tested for their efficacy using a suspension test and lab-scale laundering against two viruses: enveloped modified vaccinia virus Ankara (MVA) and nonenveloped murine norovirus (MNV). All HDD detergents effectively inactivated MVA at 30°C (titers reduced below quantification limit), whereas the hygiene rinser at 20°C exhibited lower efficacy, with 2.

A Pangenotypic Hepatitis E Virus Replication Inhibitor With High Potency in a Rat Infection Model.

Background & Aims: Hepatitis E virus (HEV) constitutes a substantial public health burden with ∼20 million human infections annually, including 3.3 million symptomatic cases. Appropriate treatment options for, in particular, HEV-infected immunocompromised patients and pregnant women are lacking, underscoring the urgent need for potent and safe antiviral drugs.

The tyrosine kinase Yes1 is a druggable host factor of HEV.

Background: HEV is a positive-sense, single-stranded RNA virus of the Hepeviridae family. Although HEV accounts for more than 3 million symptomatic cases of viral hepatitis per year, specific anti-HEV therapy and knowledge about HEV pathogenesis are scarce.

Methods: To gain a deeper understanding of the HEV infectious cycle and guide the development of novel antiviral strategies, we here used an RNAi mini screen targeting a selection of kinases, including mitogen-activated protein kinases, receptor tyrosine kinases, and Src-family kinases.

Modeling extrahepatic hepatitis E virus infection in induced human primary neurons.

Hepatitis E virus (HEV) infections are one of the most common causes of acute viral hepatitis, annually causing over 3 million symptomatic cases and 70,000 deaths worldwide. Historically, HEV was described as a hepatotropic virus, but has recently been associated with various extrahepatic manifestations including neurological disorders such as Guillain-Barré syndrome and neuralgic amyotrophy. However, the underlying pathogenesis of these neurological diseases remains largely unknown.

The glutamate receptor antagonist ifenprodil inhibits hepatitis E virus infection.

Infection with hepatitis E virus (HEV) represents a global problem, with over 20 million people infected annually. No specific antiviral drugs are available for treating HEV infection, necessitating the development of novel targeted therapeutics. Here, we report that the N-methyl-D-aspartate receptor (NMDAR) antagonist ifenprodil, a clinically approved drug used to treat idiopathic pulmonary fibrosis (IPF), is an HEV inhibitor in liver-derived cells.

Divergent autoantibody and cytokine levels in COVID-19 sepsis patients influence survival.

Studies have pointed to a decisive role of autoantibodies in the context of sepsis and severe Coronavirus disease 2019 (COVID-19), which itself often fulfills the criteria for sepsis, including dysregulated immune responses and organ dysfunction. To directly compare and further analyze the autoantibody profiles of sepsis patients with and without COVID-19, the luciferase immunoprecipitation systems (LIPS) assay was used to measure the levels of autoantibodies against a variety of clinically relevant cytokines, lung-associated proteins, other autoantigens, and antibodies against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In addition, cytokine titers were measured with the LEGENDplex™ Human Antivirus Response Panel.

MicroRNAs modulate SARS-CoV-2 infection of primary human hepatocytes by regulating the entry factors ACE2 and TMPRSS2.

Background And Aims: Severe acute respiratory syndrome coronavirus (SARS-CoV-2) preferentially infects the respiratory tract; however, several studies have implicated a multi-organ involvement. Hepatic dysfunctions caused by SARS-CoV-2 infection have been increasingly recognized and described to correlate with disease severity. To elucidate molecular factors that could contribute towards hepatic infection, we concentrated on microRNAs (miRNAs), a class of small non-coding RNAs that modulate various cellular processes and which are reported to be differentially regulated during liver injury.

Inactivation of yellow fever virus by WHO-recommended hand rub formulations and surface disinfectants.

Despite continued outbreaks of yellow fever virus (YFV) in endemic regions, data on its environmental stability or guidelines for its effective inactivation is limited. Here, we evaluated the susceptibility of the YFV 17D vaccine strain to inactivation by ethanol, 2-propanol, World Health Organization (WHO)-recommended hand rub formulations I and II, as well as surface disinfectants. In addition, two pathogenic strains were tested to compare inactivation kinetics by WHO-recommended hand rub formulations I and II.

Hepatitis E virus infections in German blood donors: results of 8 years of screening, 2015 to 2022.

BackgroundAwareness of transfusion-transmitted hepatitis E raised in recent years led to the mandatory testing of blood donations in some European countries for hepatitis E virus (HEV) RNA. However, little is known about the epidemiology of HEV infections.AimTo and describe and analyse the epidemiology of HEV infections in blood donors in Germany.

Proof of infectivity of hepatitis E virus particles from the ejaculate of chronically infected patients.

Recently, hepatitis E virus (HEV, Paslahepevirus balayani) particles were detected for the first time in the ejaculate of two chronically infected patients. Since then, we have been able to detect HEV in ejaculate in five further patients, and thus in a total of seven out of nine (78%) chronically infected men (age 36-67 years, median 56 years). In five patients, the HEV RNA concentration was more than 100-fold higher compared to the serum, while in two patients, the viral load was more than 10-fold lower.

Genetic determinants of host- and virus-derived insertions for hepatitis E virus replication.

Hepatitis E virus (HEV) is a long-neglected RNA virus and the major causative agent of acute viral hepatitis in humans. Recent data suggest that HEV has a very heterogeneous hypervariable region (HVR), which can tolerate major genomic rearrangements. In this study, we identify insertions of previously undescribed sequence snippets in serum samples of a ribavirin treatment failure patient.

Performance of sofosbuvir and NITD008 in extrahepatic neuronal cells against HEV.

Hepatitis E is an underestimated disease, leading to estimated 20 million infections and up to 70,000 deaths annually. Infections are mostly asymptomatic, but can reach mortality rates up to 25% in pregnant women or become chronic in immunocompromised patients. Hepatitis E virus (HEV) infection have been associated with a range of extrahepatic manifestations, including a spectrum of neurological symptoms.

Targeting cellular cathepsins inhibits hepatitis E virus entry.

Background And Aims: HEV is estimated to be responsible for 70,000 deaths annually, yet therapy options remain limited. In the pursuit of effective antiviral therapies, targeting viral entry holds promise and has proven effective for other viruses. However, the precise mechanisms and host factors required during HEV entry remain unclear.

Kinetics of Hepatitis E Virus Infections in Asymptomatic Persons.

To determine the kinetics of hepatitis E virus (HEV) in asymptomatic persons and to evaluate viral load doubling time and half-life, we retrospectively tested samples retained from 32 HEV RNA-positive asymptomatic blood donors in Germany. Close-meshed monitoring of viral load and seroconversion in intervals of ≈4 days provided more information about the kinetics of asymptomatic HEV infections. We determined that a typical median infection began with PCR-detectable viremia at 36 days and a maximum viral load of 2.

A comprehensive approach for evaluating the virucidal performance of domestic laundry detergents under practical conditions.

Aims: We aimed to develop a method to assess the virucidal performance of domestic laundry in a lab-scale washing machine (Rotawash) based on EN 17658.

Methods And Results: For method development, virus recovery was investigated after drying on cotton carriers for three test viruses murine norovirus (MNV), modified vaccinia virus Ankara (MVA), and bovine coronavirus (BCoV), followed by washing simulations in flasks and Rotawash. MNV and MVA demonstrated sufficient recovery from carriers after drying and washing (up to 40°C and 60 min).

Dynamic evolution of the sofosbuvir-associated variant A1343V in HEV-infected patients under concomitant sofosbuvir-ribavirin treatment.

Background & Aims: In the absence of a hepatitis E virus (HEV)-specific antiviral treatment, sofosbuvir has recently been shown to have antiviral activity against HEV . However, a variant, A1343V, that is strongly associated with viral relapse impedes treatment success. In this study, we investigated the occurrence of variants during sofosbuvir and ribavirin treatment and assessed the sensitivity of resistance-associated variants to concurrent treatment in cell culture.

Unraveling the dynamics of hepatitis C virus adaptive mutations and their impact on antiviral responses in primary human hepatocytes.

Unlabelled: Hepatitis C virus (HCV) infection progresses to chronicity in the majority of infected individuals. Its high intra-host genetic variability enables HCV to evade the continuous selection pressure exerted by the host, contributing to persistent infection. Utilizing a cell culture-adapted HCV population (p100pop) which exhibits increased replicative capacity in various liver cell lines, this study investigated virus and host determinants that underlie enhanced viral fitness.