Hemagglutinin Stability Determines Influenza A Virus Susceptibility to a Broad-Spectrum Fusion Inhibitor Arbidol.

Understanding mechanisms of resistance to antiviral inhibitors can reveal nuanced features of targeted viral mechanisms and, in turn, lead to improved strategies for inhibitor design. Arbidol is a broad-spectrum antiviral that binds to and prevents the fusion-associated conformational changes in the trimeric influenza A virus (IAV) hemagglutinin (HA). The rate-limiting step during the HA-mediated membrane fusion is the release of the hydrophobic fusion peptides from a conserved pocket on HA.

Implementation Evaluation of HUGS/Abrazos During the COVID-19 Pandemic: A Program to Foster Resiliency in Pregnancy and Early Childhood.

Early life adversity can significantly impact child development and health outcomes throughout the life course. With the COVID-19 pandemic exacerbating preexisting and introducing new sources of toxic stress, social programs that foster resilience are more necessary now than ever. The Helping Us Grow Stronger (HUGS/Abrazos) program fills a crucial need for protective buffers during the COVID-19 pandemic, which has escalated toxic stressors affecting pregnant women and families with young children.

Fostering Resilience in Pregnancy and Early Childhood During the COVID-19 Pandemic: The HUGS/Abrazos Program Design and Implementation.

Pregnancy and early childhood pose unique sensitivity to stressors such as economic instability, poor mental health, and social inequities all of which have been magnified by the COVID-19 pandemic. In absence of protective buffers, prolonged exposure to excessive, early adversity can lead to poor health outcomes with significant impact lasting beyond the childhood years. Helping Us Grow Stronger (HUGS/Abrazos) is a community-based program, designed and launched at the time of the COVID-19 surge in the Spring of 2020, that combines emergency relief, patient navigation, and direct behavioral health support to foster family resilience and mitigate the negative impacts of COVID-related toxic stress on pregnant women and families with children under age 6.

The shape of pleomorphic virions determines resistance to cell-entry pressure.

Many enveloped animal viruses produce a variety of particle shapes, ranging from small spherical to long filamentous types. Characterization of how the shape of the virion affects infectivity has been difficult because the shape is only partially genetically encoded, and most pleomorphic virus structures have no selective advantage in vitro. Here, we apply virus fractionation using low-force sedimentation, as well as antibody neutralization coupled with RNAScope, single-particle membrane fusion experiments and stochastic simulations to evaluate the effects of differently shaped influenza A viruses and influenza viruses pseudotyped with Ebola glycoprotein on the infection of cells.

Directed Evolution of an Influenza Reporter Virus To Restore Replication and Virulence and Enhance Noninvasive Bioluminescence Imaging in Mice.

Reporter viruses provide a powerful tool to study infection, yet incorporating a nonessential gene often results in virus attenuation and genetic instability. Here, we used directed evolution of a luciferase-expressing pandemic H1N1 (pH1N1) 2009 influenza A virus in mice to restore replication kinetics and virulence, increase the bioluminescence signal, and maintain reporter gene expression. An unadapted pH1N1 virus with inserted into the 5' end of the PA gene segment grew to titers 10-fold less than those of the wild type in MDCK cells and in DBA/2 mice and was less virulent.