Eurasian 1C swine influenza A virus exhibits high pandemic risk traits.

Recent surveillance has identified an expansion of swine H1 1C influenza viruses in Eurasian swine. Since 2010, at least 21 spillover events of 1C virus into humans have been detected and three of these occurred from July to December of 2023. Pandemic risk assessment of H1 1C influenza virus revealed that individuals born after 1950 had limited cross-reactive antibodies, confirming that they are antigenically novel viruses.

Performance of established disease severity scores in predicting severe outcomes among adults hospitalized with influenza-FluSurv-NET, 2017-2018.

Background: Influenza is a substantial cause of annual morbidity and mortality; however, correctly identifying those patients at increased risk for severe disease is often challenging. Several severity indices have been developed; however, these scores have not been validated for use in patients with influenza. We evaluated the discrimination of three clinical disease severity scores in predicting severe influenza-associated outcomes.

Immune correlates of protection following Rift Valley fever virus vaccination.

Rift Valley fever virus (RVFV) is a hemorrhagic fever virus with the potential for significant economic and public health impact. Vaccination with an attenuated strain, DelNSsRVFV, provides protection from an otherwise lethal RVFV challenge, but mechanistic determinants of protection are undefined. In this study, a murine model was used to assess the contributions of humoral and cellular immunity to DelNSsRVFV-mediated protection.

Genetic diversity of collaborative cross mice enables identification of novel rift valley fever virus encephalitis model.

Rift Valley fever (RVF) is an arboviral disease of humans and livestock responsible for severe economic and human health impacts. In humans, RVF spans a variety of clinical manifestations, ranging from an acute flu-like illness to severe forms of disease, including late-onset encephalitis. The large variations in human RVF disease are inadequately represented by current murine models, which overwhelmingly die of early-onset hepatitis.

Relative and Absolute Effectiveness of High-Dose and Standard-Dose Influenza Vaccine Against Influenza-Related Hospitalization Among Older Adults-United States, 2015-2017.

Background: Seasonal influenza causes substantial morbidity and mortality in older adults. High-dose inactivated influenza vaccine (HD-IIV), with increased antigen content compared to standard-dose influenza vaccines (SD-IIV), is licensed for use in people aged ≥65 years. We sought to evaluate the effectiveness of HD-IIV and SD-IIV for prevention of influenza-associated hospitalizations.

Influenza virus-related critical illness: prevention, diagnosis, treatment.

Annual seasonal influenza epidemics of variable severity result in significant morbidity and mortality in the United States (U.S.) and worldwide.

Interim Estimates of 2018-19 Seasonal Influenza Vaccine Effectiveness - United States, February 2019.

In the United States, annual vaccination against seasonal influenza is recommended for all persons aged ≥6 months (https://www.cdc.gov/flu/protect/whoshouldvax.

Pediatric influenza and illness severity: what is known and what questions remain?

Purpose Of Review: Influenza causes a range of illnesses in children, from uncomplicated self-limited illness to severe disease and death. This review provides an update on the severity and burden of influenza in US children over recent seasons.

Recent Findings: The 2017-2018 influenza season was widespread and severe across all ages, including children.

Improving Influenza Testing and Treatment in Hospitalized Children.

Objectives: National guidelines recommend influenza testing for children hospitalized with influenza-like illness (ILI) during influenza season and treatment of those with confirmed influenza. Using quality improvement methods, we sought to increase influenza testing and treatment of children admitted to our hospital medicine service with ILI from 65% to 90% during the 2014-2015 influenza season.

Methods: We targeted several key drivers using multiple plan-do-study-act cycles.

Diminished reovirus capsid stability alters disease pathogenesis and littermate transmission.

Reovirus is a nonenveloped mammalian virus that provides a useful model system for studies of viral infections in the young. Following internalization into host cells, the outermost capsid of reovirus virions is removed by endosomal cathepsin proteases. Determinants of capsid disassembly kinetics reside in the viral σ3 protein.

Genetic determinants of reovirus pathogenesis in a murine model of respiratory infection.

Many viruses invade mucosal surfaces to establish infection in the host. Some viruses are restricted to mucosal surfaces, whereas others disseminate to sites of secondary replication. Studies of strain-specific differences in reovirus mucosal infection and systemic dissemination have enhanced an understanding of viral determinants and molecular mechanisms that regulate viral pathogenesis.

Molecular determinants of proteolytic disassembly of the reovirus outer capsid.

Following attachment and internalization, mammalian reoviruses undergo intracellular proteolytic disassembly followed by viral penetration into the cytoplasm. The initiating event in reovirus disassembly is the cathepsin-mediated proteolytic degradation of viral outer capsid protein σ3. A single tyrosine-to-histidine mutation at amino acid 354 (Y354H) of strain type 3 Dearing (T3D) σ3 enhances reovirus disassembly and confers resistance to protease inhibitors such as E64.

Murine hepatitis virus nonstructural protein 4 regulates virus-induced membrane modifications and replication complex function.

Positive-strand RNA viruses induce modifications of cytoplasmic membranes to form replication complexes. For coronaviruses, replicase nonstructural protein 4 (nsp4) has been proposed to function in the formation and organization of replication complexes. Murine hepatitis virus (MHV) nsp4 is glycosylated at residues Asn176 (N176) and N237 during plasmid expression of nsp4 in cells.

Genetic and pharmacologic alteration of cathepsin expression influences reovirus pathogenesis.

The cathepsin family of endosomal proteases is required for proteolytic processing of several viruses during entry into host cells. Mammalian reoviruses utilize cathepsins B (Ctsb), L (Ctsl), and S (Ctss) for disassembly of the virus outer capsid and activation of the membrane penetration machinery. To determine whether cathepsins contribute to reovirus tropism, spread, and disease outcome, we infected 3-day-old wild-type (wt), Ctsb(-/-), Ctsl(-/-), and Ctss(-/-) mice with the virulent reovirus strain T3SA+.