ATG9A regulates the dissociation of recycling endosomes from microtubules to form liquid influenza A virus inclusions.

It is now established that many viruses that threaten public health establish condensates via phase transitions to complete their lifecycles, and knowledge on such processes may offer new strategies for antiviral therapy. In the case of influenza A virus (IAV), liquid condensates known as viral inclusions, concentrate the 8 distinct viral ribonucleoproteins (vRNPs) that form IAV genome and are viewed as sites dedicated to the assembly of the 8-partite genomic complex. Despite not being delimited by host membranes, IAV liquid inclusions accumulate host membranes inside as a result of vRNP binding to the recycling endocytic marker Rab11a, a driver of the biogenesis of these structures.

Challenges in Imaging Analyses of Biomolecular Condensates in Cells Infected with Influenza A Virus.

Biomolecular condensates are crucial compartments within cells, relying on their material properties for function. They form and persist through weak, transient interactions, often undetectable by classical biochemical approaches. Hence, microscopy-based techniques have been the most reliable methods to detail the molecular mechanisms controlling their formation, material properties, and alterations, including dissolution or phase transitions due to cellular manipulation and disease, and to search for novel therapeutic strategies targeting biomolecular condensates.

Defining basic rules for hardening influenza A virus liquid condensates.

In biological systems, liquid and solid-like biomolecular condensates may contain the same molecules but their behaviour, including movement, elasticity, and viscosity, is different on account of distinct physicochemical properties. As such, it is known that phase transitions affect the function of biological condensates and that material properties can be tuned by several factors including temperature, concentration, and valency. It is, however, unclear if some factors are more efficient than others at regulating their behaviour.

PI4P and BLOC-1 remodel endosomal membranes into tubules.

Intracellular trafficking is mediated by transport carriers that originate by membrane remodeling from donor organelles. Tubular carriers contribute to the flux of membrane lipids and proteins to acceptor organelles, but how lipids and proteins impose a tubular geometry on the carriers is incompletely understood. Using imaging approaches on cells and in vitro membrane systems, we show that phosphatidylinositol-4-phosphate (PI4P) and biogenesis of lysosome-related organelles complex 1 (BLOC-1) govern the formation, stability, and functions of recycling endosomal tubules.

Saliva molecular testing bypassing RNA extraction is suitable for monitoring and diagnosing SARS-CoV-2 infection in children.

Background: Adults are being vaccinated against SARS-CoV-2 worldwide, but the longitudinal protection of these vaccines is uncertain, given the ongoing appearance of SARS-CoV-2 variants. Children remain largely unvaccinated and are susceptible to infection, with studies reporting that they actively transmit the virus even when asymptomatic, thus affecting the community.

Methods: We investigated if saliva is an effective sample for detecting SARS-CoV-2 RNA and antibodies in children, and associated viral RNA levels to infectivity.

Influenza A virus ribonucleoproteins form liquid organelles at endoplasmic reticulum exit sites.

Influenza A virus has an eight-partite RNA genome that during viral assembly forms a complex containing one copy of each RNA. Genome assembly is a selective process driven by RNA-RNA interactions and is hypothesized to lead to discrete punctate structures scattered through the cytosol. Here, we show that contrary to the accepted view, formation of these structures precedes RNA-RNA interactions among distinct viral ribonucleoproteins (vRNPs), as they assemble in cells expressing only one vRNP type.

KIF13A mediates trafficking of influenza A virus ribonucleoproteins.

Influenza A is a rapidly evolving virus that is successful in provoking periodic epidemics and occasional pandemics in humans. Viral assembly is complex as the virus incorporates an eight-partite genome of RNA (in the form of viral ribonucleoproteins, vRNPs), and viral genome assembly - with its implications to public health - is not completely understood. It has previously been reported that vRNPs are transported to the cell surface on Rab11-containing vesicles by using microtubules but, so far, no molecular motor has been assigned to the process.

Clustering of Rab11 vesicles in influenza A virus infected cells creates hotspots containing the 8 viral ribonucleoproteins.

Influenza A virus is an important human pathogen causative of yearly epidemics and occasional pandemics. The ability to replicate within the host cell is a determinant of virulence, amplifying viral numbers for host-to-host transmission. This process requires multiple rounds of entering permissive cells, replication, and virion assembly at the plasma membrane, the site of viral budding and release.

Recycling Endosomes and Viral Infection.

Many viruses exploit specific arms of the endomembrane system. The unique composition of each arm prompts the development of remarkably specific interactions between viruses and sub-organelles. This review focuses on the viral-host interactions occurring on the endocytic recycling compartment (ERC), and mediated by its regulatory Ras-related in brain (Rab) GTPase Rab11.

Influenza A virus ribonucleoproteins modulate host recycling by competing with Rab11 effectors.

Influenza A virus assembly is an unclear process, whereby individual virion components form an infectious particle. The segmented nature of the influenza A genome imposes a problem to assembly because it requires packaging of eight distinct RNA particles (vRNPs). It also allows genome mixing from distinct parental strains, events associated with influenza pandemic outbreaks.

Studies in the mouse model identify strain variability as a major determinant of disease outcome in Leishmania infantum infection.

Background: Visceral leishmaniasis is a severe and potentially fatal disease caused by protozoa of the genus Leishmania, transmitted by phlebotomine sandflies. In Europe and the Mediterranean region, L. infantum is the commonest agent of visceral leishmaniasis, causing a wide spectrum of clinical manifestations, including asymptomatic carriage, cutaneous lesions and severe visceral disease.

Iron in intracellular infection: to provide or to deprive?

Due to their chemical versatility, transition metals were incorporated as cofactors for several basic metabolic pathways in living organisms. This same characteristic makes them potentially harmful, since they can be engaged in deleterious reactions like Fenton chemistry. As such, organisms have evolved highly specialized mechanisms to supply their own metal needs while keeping their toxic potential in check.

Iron overload favors the elimination of Leishmania infantum from mouse tissues through interaction with reactive oxygen and nitrogen species.

Iron plays a central role in host-parasite interactions, since both intervenients need iron for survival and growth, but are sensitive to iron-mediated toxicity. The host's iron overload is often associated with susceptibility to infection. However, it has been previously reported that iron overload prevented the growth of Leishmania major, an agent of cutaneous leishmaniasis, in BALB/c mice.

Lipoarabinomannan mannose caps do not affect mycobacterial virulence or the induction of protective immunity in experimental animal models of infection and have minimal impact on in vitro inflammatory responses.

Mannose-capped lipoarabinomannan (ManLAM) is considered an important virulence factor of Mycobacterium tuberculosis. However, while mannose caps have been reported to be responsible for various immunosuppressive activities of ManLAM observed in vitro, there is conflicting evidence about their contribution to mycobacterial virulence in vivo. Therefore, we used Mycobacterium bovis BCG and M.

Peptidomimetic and organometallic derivatives of primaquine active against Leishmania infantum.

The current treatment of visceral leishmaniasis is made difficult by the low efficacy, elevated costs, low bioavailability, and high toxicity of many of the available drugs. Primaquine, an antimalarial 8-aminoquinoline, displays activity against Leishmania spp., and several of its derivatives have been developed as potential antileishmanial drugs.