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Double membrane vesicles (DMV) are used as replication organelles by several RNA viruses. Applying proteomics and lipidomics, Tabata and Prasad et al. find that two cellular acyltransferases (AGPAT1/2), responsible for synthesis of phosphatidic acid, play a role in the DMV-biogenesis of HCV and SARS-CoV-2, highlighting a common biogenesis mechanism for evolutionary distant positive-strand RNA viruses.

Background & Aims: A single hepatitis B virus (HBV) particle is sufficient to establish chronic infection of the liver after intravenous injection, suggesting that the virus targets hepatocytes via a highly efficient transport pathway. We therefore investigated whether HBV uses a physiological liver-directed pathway that supports specific host-cell targeting in vivo. Methods: We established the ex vivo perfusion of intact human liver tissue that recapitulates the liver physiology to investigate HBV liver targeting. This model allowed us to investigate virus-host cell interactions in a cellular microenvironment mimicking the in vivo situation. Results: HBV was rapidly sequestered by liver macrophages within 1 hour after a virus pulse perfusion but was detected in hepatocytes only after 16 hours. We found that HBV associates with lipoproteins in serum and within machrophages. Electron and immunofluorescence microscopy corroborated a co-localization in recycling endosomes within peripheral and liver macrophages. Recycling endosomes accumulated HBV and cholesterol, followed by transport of HBV back to the cell surface along the cholesterol efflux pathway. To reach hepatocytes as final target cells, HBV was able to utilize the hepatocyte-directed cholesterol transport machinery of macrophages. Conclusions: Our results propose that by binding to liver targeted lipoproteins and using the reverse cholesterol transport pathway of macrophages, HBV hijacks the physiological lipid transport pathways to the liver to most efficiently reach its target organ. This may involve transinfection of liver macrophages and result in deposition of HBV in the perisinusoidal space from where HBV can bind its receptor on hepatocytes.

Because our civilization has relied on pesticides to fight weeds, insects, and diseases since antiquity, the use of these chemicals has become natural and exclusive. Unfortunately, the use of pesticides has progressively had alarming effects on water quality, biodiversity, and human health. This paper proposes to improve farming practices by replacing pesticides with a laser-based robotic approach. This study focused on the neutralization of aphids, as they are among the most harmful pests for crops and complex to control. With the help of deep learning, we developed a mobile robot that spans crop rows, locates aphids, and neutralizes them with laser beams. We have built a prototype with the sole purpose of validating the localization-neutralization loop on a single seedling row. The experiments performed in our laboratory demonstrate the feasibility of detecting different lines of aphids (50% detected at 3 cm/s) and of neutralizing them (90% mortality) without impacting the growth of their host plants. The results are encouraging since aphids are one of the most challenging crop pests to eradicate. However, enhancements in detection and mainly in targeting are necessary to be useful in a real farming context. Moreover, robustness regarding field conditions should be evaluated.

The hepatitis C virus (HCV) life cycle is highly regulated and characterized by a step-wise succession of interactions between viral and host cell proteins resulting in the assembly of macromolecular complexes, which catalyse genome replication and/or virus production. Non-structural (NS) protein 3, comprising a protease and a helicase domain, is involved in orchestrating these processes by undergoing protein interactions in a temporal fashion. Recently, we identified a multifunctional NS3 protease surface patch promoting pivotal protein-protein interactions required for early steps of the HCV life cycle, including NS3-mediated NS2 protease activation and interactions required for replicase assembly. In this work, we extend this knowledge by identifying further NS3 surface determinants important for NS5A hyperphosphorylation, replicase assembly or virion morphogenesis, which map to protease and helicase domain and form a contiguous NS3 surface area. Functional interrogation led to the identification of phylogenetically conserved amino acid positions exerting a critical function in virion production without affecting RNA replication. These findings illustrate that NS3 uses a multipurpose protein surface to orchestrate the step-wise assembly of functionally distinct multiprotein complexes. Taken together, our data provide a basis to dissect the temporal formation of viral multiprotein complexes required for the individual steps of the HCV life cycle.

The advent of telerobotic systems has revolutionized various aspects of the industry and human life. This technology is designed to augment human sensorimotor capabilities to extend them beyond natural competence. Classic examples are space and underwater applications when distance and access are the two major physical barriers to be combated with this technology. In modern examples, telerobotic systems have been used in several clinical applications, including teleoperated surgery and telerehabilitation. In this regard, there has been a significant amount of research and development due to the major benefits in terms of medical outcomes. Recently telerobotic systems are combined with advanced artificial intelligence modules to better share the agency with the operator and open new doors of medical automation. In this review paper, we have provided a comprehensive analysis of the literature considering various topologies of telerobotic systems in the medical domain while shedding light on different levels of autonomy for this technology, starting from direct control, going up to command-tracking autonomous telerobots. Existing challenges, including instrumentation, transparency, autonomy, stochastic communication delays, and stability, in addition to the current direction of research related to benefit in telemedicine and medical automation, and future vision of this technology, are discussed in this review paper.