Structural basis for nuclear import of adeno-associated virus serotype 6 capsid protein.

Adeno-associated viruses (AAVs) are the most extensively researched viral vectors for gene therapy globally. The AAV viral protein 1 (VP1) N-terminus controls the capsid's ability to translocate into the cell nucleus; however, the exact mechanism of this process is largely unknown. In this study, we sought to elucidate the precise interactions between AAV serotype 6 (AAV6), a promising vector for immune disorders, and host transport receptors responsible for vector nuclear localization.

Structural basis for nuclear import of bat adeno-associated virus capsid protein.

Adeno-associated viruses (AAV) are one of the world's most promising gene therapy vectors and as a result, are one of the most intensively studied viral vectors. Despite a wealth of research into these vectors, the precise characterisation of AAVs to translocate into the host cell nucleus remains unclear. Recently we identified the nuclear localization signals of an AAV porcine strain and determined its mechanism of binding to host importin proteins.

Structural Determination of the Australian Bat Lyssavirus Nucleoprotein and Phosphoprotein Complex.

Australian bat lyssavirus (ABLV) shows similar clinical symptoms as rabies, but there are currently no protein structures available for ABLV proteins. In lyssaviruses, the interaction between nucleoprotein (N) and phosphoprotein (N) in the absence of RNA generates a complex (NP) that is crucial for viral assembly, and understanding the interface between these two proteins has the potential to provide insight into a key feature: the viral lifecycle. In this study, we used recombinant chimeric protein expression and X-ray crystallography to determine the structure of ABLV nucleoprotein bound to residues 1-40 of its phosphoprotein chaperone.

Henipavirus Matrix Protein Employs a Non-Classical Nuclear Localization Signal Binding Mechanism.

Nipah virus (NiV) and Hendra virus (HeV) are highly pathogenic species from the genus within the paramyxovirus family and are harbored by Flying Fox species. Henipaviruses cause severe respiratory disease, neural symptoms, and encephalitis in various animals and humans, with human mortality rates exceeding 70% in some NiV outbreaks. The henipavirus matrix protein (M), which drives viral assembly and budding of the virion, also performs non-structural functions as a type I interferon antagonist.

Structural Characterization of Porcine Adeno-Associated Virus Capsid Protein with Nuclear Trafficking Protein Importin Alpha Reveals a Bipartite Nuclear Localization Signal.

Adeno-associated viruses (AAV) are important vectors for gene therapy, and accordingly, many aspects of their cell transduction pathway have been well characterized. However, the specific mechanisms that AAV virions use to enter the host nucleus remain largely unresolved. We therefore aimed to reveal the interactions between the AAV Cap protein and the nuclear transport protein importin alpha (IMPα) at an atomic resolution.

Tick-borne encephalitis virus capsid protein induces translational shutoff as revealed by its structural-biological analysis.

Tick-borne encephalitis virus (TBEV) is the most medically relevant tick-transmitted Flavivirus in Eurasia, targeting the host central nervous system and frequently causing severe encephalitis. The primary function of its capsid protein (TBEVC) is to recruit the viral RNA and form a nucleocapsid. Additional functionality of Flavivirus capsid proteins has been documented, but further investigation is needed for TBEVC.

Long-Term Esca Monitoring Reveals Disease Impacts on Fruit Yield and Wine Quality.

Esca is a widespread grapevine trunk disease, and a global increase in esca incidence has been observed in recent decades. Estimates attribute considerable economic losses to esca, and the disease is considered one of the major causes of vine mortality and vineyard dieback. However, accurate quantification of esca incidence is difficult due to symptom inconsistency, and there are very few studies precisely quantifying yield losses and impacts on fruit composition and wine quality.

Correction: Tsimbalyuk et al. The Intrinsically Disordered W Protein Is Multifunctional during Henipavirus Infection, Disrupting Host Signalling Pathways and Nuclear Import. , , 1913.

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MERS-CoV ORF4b employs an unusual binding mechanism to target IMPα and block innate immunity.

The MERS coronavirus (MERS-CoV) is a highly pathogenic, emerging virus that produces accessory proteins to antagonize the host innate immune response. The MERS-CoV ORF4b protein has been shown to bind preferentially to the nuclear import adapter IMPα3 in infected cells, thereby inhibiting NF-κB-dependent innate immune responses. Here, we report high-resolution structures of ORF4b bound to two distinct IMPα family members.

A scoping review of live wildlife trade in markets worldwide.

Wet markets sell fresh food and are a global phenomenon. They are important for food security in many regions worldwide but have come under scrutiny due to their potential role in the emergence of infectious diseases. The sale of live wildlife has been highlighted as a particular risk, and the World Health Organisation has called for the banning of live, wild-caught mammalian species in markets unless risk assessment and effective regulations are in place.

Structural characterization of the porcine adeno-associated virus Po1 capsid protein binding to the nuclear trafficking protein importin alpha.

Adeno-associated viruses (AAVs) are key vectors for gene therapy; thus, many aspects of their cell transduction pathway have been revealed in detail. However, the specific mechanisms AAV virions use to enter the host nucleus remain largely unresolved. We therefore aimed to reveal the structural interactions between the AAV capsid (Cap) protein and the nuclear transport protein importin alpha (IMPα).

Endomembrane targeting of human OAS1 p46 augments antiviral activity.

Many host RNA sensors are positioned in the cytosol to detect viral RNA during infection. However, most positive-strand RNA viruses replicate within a modified organelle co-opted from intracellular membranes of the endomembrane system, which shields viral products from cellular innate immune sensors. Targeting innate RNA sensors to the endomembrane system may enhance their ability to sense RNA generated by viruses that use these compartments for replication.

A scoping review of African swine fever virus spread between domestic and free-living pigs.

Since 2007, African swine fever virus (ASFV) has spread to countries in Europe, Asia and Oceania and has caused devastating impacts on pigs and the pork industry. Transmission can be direct or indirect, and epidemiologic scenarios have been described in which spread occurs between free-living and domestic pigs. The purpose of this scoping review was to identify primary research in which authors made statements to support ASFV transmission between free-living and domestic pigs and assess the circumstances in which transmission events occurred.

Milestone Learning Trajectories of Residents at Five Anesthesiology Residency Programs.

Every six months, residency programs report their trainees' Milestones Level achievement to the Accreditation Council for Graduate Medical Education (ACGME). Milestones should enable the learner and training program to know an individual's competency development trajectory. Milestone Level ratings for residents grouped by specialty (e.

Structural Perspectives of Beak and Feather Disease Virus and Porcine Circovirus Proteins.

Circoviruses represent a rapidly expanding group of viruses that infect both vertebrate and invertebrate hosts. Members are responsible for diseases of veterinary and economic importance, including postweaning multisystemic wasting syndrome in pigs, and beak and feather disease (BFD) in birds. These viruses are associated with lymphoid depletion and immunosuppressive conditions in infected animals leading to systemic illness.

The Structural Features of Matrix Protein Driving Intracellular Trafficking.

Henipaviruses are single-stranded RNA viruses that have recently emerged as zoonotic pathogens, capable of causing severe acute respiratory disease and encephalitis in humans. The prototypical henipaviruses, and , are a major health concern as they have high mortality rates and no currently approved human vaccine or drug therapy. Understanding the mechanisms of viral replication and pathogenicity is of critical importance for therapeutic developments.

The Intrinsically Disordered W Protein Is Multifunctional during Henipavirus Infection, Disrupting Host Signalling Pathways and Nuclear Import.

Nipah and Hendra viruses are highly pathogenic, zoonotic henipaviruses that encode proteins that inhibit the host's innate immune response. The W protein is one of four products encoded from the P gene and binds a number of host proteins to regulate signalling pathways. The W protein is intrinsically disordered, a structural attribute that contributes to its diverse host protein interactions.

Proteome-Wide Zika Virus CD4 T Cell Epitope and HLA Restriction Determination.

Zika virus (ZIKV) is a mosquito-borne pathogen that caused an epidemic in 2015-2016. ZIKV-specific T cell responses are functional in animal infection models, and helper CD4 T cells promote avid Abs in the vaccine context. The small volumes of blood available from field research limit the determination of T cell epitopes for complex microbes such as ZIKV.

Flavivirus Nonstructural Protein NS5 Dysregulates HSP90 to Broadly Inhibit JAK/STAT Signaling.

Pathogenic flaviviruses antagonize host cell Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling downstream of interferons α/β. Here, we show that flaviviruses inhibit JAK/STAT signaling induced by a wide range of cytokines beyond interferon, including interleukins. This broad inhibition was mapped to viral nonstructural protein 5 (NS5) binding to cellular heat shock protein 90 (HSP90), resulting in reduced Janus kinase-HSP90 interaction and thus destabilization of unchaperoned JAKs (and other kinase clients) of HSP90 during infection by , West Nile virus, and Japanese encephalitis virus.

Immune Evasion Strategies Used by Zika Virus to Infect the Fetal Eye and Brain.

Zika virus (ZIKV) is a mosquito-transmitted flavivirus that caused a public health emergency in the Americas when an outbreak in Brazil became linked to congenital microcephaly. Understanding how ZIKV could evade the innate immune defenses of the mother, placenta, and fetus has become central to determining how the virus can traffic into the fetal brain. ZIKV, like other flaviviruses, evades host innate immune responses by leveraging viral proteins and other processes that occur during viral replication to allow spread to the placenta.

Impact of vine water status on berry mass and berry tissue development of Cabernet franc (Vitis vinifera L.), assessed at berry level.

Background: Berry size is considered an important quality factor in red wine production. The objective of this work was to study the effect of vine water status on berry mass in field conditions, with a specific focus on berry tissue masses.

Results: The study was carried out over 2 years in a plot located in Sicily (Italy).