20 research outputs found

    Ebolavirus Is Internalized into Host Cells via Macropinocytosis in a Viral Glycoprotein-Dependent Manner

    Get PDF
    Ebolavirus (EBOV) is an enveloped, single-stranded, negative-sense RNA virus that causes severe hemorrhagic fever with mortality rates of up to 90% in humans and nonhuman primates. Previous studies suggest roles for clathrin- or caveolae-mediated endocytosis in EBOV entry; however, ebolavirus virions are long, filamentous particles that are larger than the plasma membrane invaginations that characterize clathrin- or caveolae-mediated endocytosis. The mechanism of EBOV entry remains, therefore, poorly understood. To better understand Ebolavirus entry, we carried out internalization studies with fluorescently labeled, biologically contained Ebolavirus and Ebolavirus-like particles (Ebola VLPs), both of which resemble authentic Ebolavirus in their morphology. We examined the mechanism of Ebolavirus internalization by real-time analysis of these fluorescently labeled Ebolavirus particles and found that their internalization was independent of clathrin- or caveolae-mediated endocytosis, but that they co-localized with sorting nexin (SNX) 5, a marker of macropinocytosis-specific endosomes (macropinosomes). Moreover, the internalization of Ebolavirus virions accelerated the uptake of a macropinocytosis-specific cargo, was associated with plasma membrane ruffling, and was dependent on cellular GTPases and kinases involved in macropinocytosis. A pseudotyped vesicular stomatitis virus possessing the Ebolavirus glycoprotein (GP) also co-localized with SNX5 and its internalization and infectivity were affected by macropinocytosis inhibitors. Taken together, our data suggest that Ebolavirus is internalized into cells by stimulating macropinocytosis in a GP-dependent manner. These findings provide new insights into the lifecycle of Ebolavirus and may aid in the development of therapeutics for Ebolavirus infection

    Auditory information enhances post-sensory visual evidence during rapid multisensory decision-making

    Get PDF
    Despite recent progress in understanding multisensory decision-making, a conclusive mechanistic account of how the brain translates the relevant evidence into a decision is lacking. Specifically, it remains unclear whether perceptual improvements during rapid multisensory decisions are best explained by sensory (i.e., ‘Early’) processing benefits or post-sensory (i.e., ‘Late’) changes in decision dynamics. Here, we employ a well-established visual object categorisation task in which early sensory and post-sensory decision evidence can be dissociated using multivariate pattern analysis of the electroencephalogram (EEG). We capitalize on these distinct neural components to identify when and how complementary auditory information influences the encoding of decision-relevant visual evidence in a multisensory context. We show that it is primarily the post-sensory, rather than the early sensory, EEG component amplitudes that are being amplified during rapid audiovisual decision-making. Using a neurally informed drift diffusion model we demonstrate that a multisensory behavioral improvement in accuracy arises from an enhanced quality of the relevant decision evidence, as captured by the post-sensory EEG component, consistent with the emergence of multisensory evidence in higher-order brain areas

    A review of zoonotic infection risks associated with the wild meat trade in Malaysia.

    Get PDF
    The overhunting of wildlife for food and commercial gain presents a major threat to biodiversity in tropical forests and poses health risks to humans from contact with wild animals. Using a recent survey of wildlife offered at wild meat markets in Malaysia as a basis, we review the literature to determine the potential zoonotic infection risks from hunting, butchering and consuming the species offered. We also determine which taxa potentially host the highest number of pathogens and discuss the significant disease risks from traded wildlife, considering how cultural practices influence zoonotic transmission. We identify 51 zoonotic pathogens (16 viruses, 19 bacteria and 16 parasites) potentially hosted by wildlife and describe the human health risks. The Suidae and the Cervidae families potentially host the highest number of pathogens. We conclude that there are substantial gaps in our knowledge of zoonotic pathogens and recommend performing microbial food safety risk assessments to assess the hazards of wild meat consumption. Overall, there may be considerable zoonotic risks to people involved in the hunting, butchering or consumption of wild meat in Southeast Asia, and these should be considered in public health strategies
    corecore