ETIDIOH - NEW

Abstract H5Nx viruses continue to wreak havoc in avian and mammalian species worldwide. The virus distinguishes itself by the ability to replicate to high titers and transmit efficiently in a wide variety of hosts in diverse climatic environments. Fortunately, transmission to and between humans is scarce . Yet, if such an event were to occur, it could spark a pandemic as humans are immunologically naive to H5 viruses. A significant determinant of transmission to and between humans is the ability of the influenza A virus hemagglutinin (HA) protein to shift from an avian-type to a human-type receptor specificity . Here, we demonstrate that a 2016 2.3.4.4e virus HA can convert to human-type receptor binding via a single Q226L mutation , in contrast to a cleavage-modified 2016 2.3.4.4b virus HA . Using glycan arrays, x-ray structural analyses, tissue- and direct glycan binding, we show that L133adelta and 227Q are vital for this phenotype. Thus, whereas the 2.3.4.4e virus HA only needs a s...

Abstract We compared virus replication and host responses in human alveolar epithelium infected with highly pathogenic avian influenza (HPAI) A( H5N1 ) viruses. A/Vietnam/1203/2004 replicated most efficiently, followed by A/Texas/37/2024 , then A/bovine/Ohio/B24OSU-342/2024 . Induction of interferon-stimulated genes was lower with A/Texas/37/2024 and A/bovine/Ohio/B24OSU-342/2024, which may indicate a reduced disease severity of those viruses. Source: Emerging Infectious Diseases Journal,  https://wwwnc.cdc.gov/eid/article/31/2/24-1147_article _____

Abstract The COVID-19 pandemic has been driven by SARS-CoV-2 variants with enhanced transmission and immune escape . Apart from extensive evolution in the Spike protein , non-Spike mutations are accumulating across the entire viral genome and their functional impact is not well understood. To address the contribution of these mutations, we reconstructed genomes of recent Omicron variants with disabled Spike expression (replicons) to systematically compare their RNA replication capabilities independently from Spike. We also used a single reference replicon and complemented it with various Omicron variant Spike proteins to quantify viral entry capabilities in single-round infection assays. Viral entry and RNA replication were negatively correlated , suggesting that as variants evolve reduced entry functions under growing immune pressure on Spike, RNA replication increases as a compensatory mechanism. We identified multiple mutations across the viral genome that enhanced viral RNA replica...

ABSTRACT Several viruses, including influenza A virus (IAV), encode viral factors to hijack cellular RNA biogenesis processes to direct the degradation of host mRNAs, termed “host shutoff.” Host shutoff enables viruses to simultaneously reduce antiviral responses and provides preferential access for viral mRNAs to cellular translation machinery . IAV PA-X is one of these factors that selectively shuts off the global host genes. However, the specific role of PA-X host shutoff activity in viral fitness of IAV remains poorly understood. Herein, we successfully mapped PA-X 100 V as a novel site important for host shutoff of the H7N9 and H5N1 viruses . By analysing the polymorphism of this residue in various subtype viruses, we found that PA-X 100 was highly variable in H7N9 viruses. Structural analysis revealed that 100 V was generally close to the PA-X endonuclease active site , which may account for its host shutoff activity. By generating the corresponding mutant viruses derived from th...

Abstract Influenza A viruses (IAVs) initially infect a few host cells , and the infection subsequently spreads to neighboring cells . However, the molecular mechanisms underlying this expansion remain unclear. Here, we show that IAV infection upregulates the frequency of intercellular calcium wave propagations (iCWPs) that mediate the spread of IAVs. ADP released from initially infected cells mediated iCWPs via the P2Y1 receptor. The generation of iCWPs and spread of viral infection were inhibited by a P2Y1 antagonist. Enhanced endocytosis in the surrounding cells that received ADP signaling upregulated viral entry. Expression of IAV matrix protein 2 (M2) in initially infected cells triggered iCWPs through ADP diffusion, thereby increasing infection, whereas an ion permeability-deficient mutation of M2 or inhibition of its ion channel activity suppressed iCWPs. Therefore, intercellular calcium signaling is essential for early expansion and potential establishment of IAV infection, whic...