Ubiquitylation is one of the most versatile protein post-translational modifications and is frequently altered during virus infections. Here we employed a functional proteomics screen to identify host proteins that are differentially ubiquitylated upon dengue virus (DENV) infection. Among the several differentially modified proteins identified in infected cells was AUP1, a lipid droplet-localized type-III membrane protein, which exists predominantly in the mono-ubiquitylated form. AUP1 associated with DENV NS4A and relocalized from lipid droplets to autophagosomes upon infection. Virus production was abolished in cells deleted for AUP1 or expressing an AUP1 acyltransferase domain mutant. Ubiquitylation disrupted the AUP1-NS4A interaction, resulting in inhibited acyltransferase activity, defective lipophagy, and attenuated virus production. Our results show that DENV-NS4A exploits the acyltransferase activity of AUP1 to trigger lipophagy, a process regulated by ubiquitylation. This mechanism appears to be a general phenomenon in biogenesis of flaviviruses and underscores the critical role of post-translational modifications in virus infections.
Background: To date, very few cellular factors required for secretion of flaviviruses have been described. Results: Simultaneous depletion of class II Arf (Arf4 and Arf5) blocks dengue flavivirus secretion, without altering the constitutive secretory pathway. Dengue glycoprotein prM interacts with Arf4 and Arf5. Conclusion: Arf4 and Arf5 play a crucial role in dengue flavivirus secretion. Significance: Our findings reveal a molecular mechanism of dengue flavivirus secretion.
Membrane receptors at the surface of target cells are key host factors for virion entry; however, it is unknown whether trafficking and secretion of progeny virus requires host intracellular receptors. In this study, we demonstrate that dengue virus (DENV) interacts with KDEL receptors (KDELR), which cycle between the ER and Golgi apparatus, for vesicular transport from ER to Golgi. Depletion of KDELR by siRNA reduced egress of both DENV progeny and recombinant subviral particles (RSPs). Coimmunoprecipitation of KDELR with dengue structural protein prM required three positively charged residues at the N terminus, whose mutation disrupted protein interaction and inhibited RSP transport from the ER to the Golgi. Finally, siRNA depletion of class II Arfs, which results in KDELR accumulation in the Golgi, phenocopied results obtained with mutagenized prME and KDELR knockdown. Our results have uncovered a function for KDELR as an internal receptor involved in DENV trafficking.
Among the various host cellular processes that are hijacked by flaviviruses, few mechanisms have been described with regard to viral egress. Here we investigate how flaviviruses exploit Src family kinases (SFKs) for exit from infected cells. We identify Lyn as a critical component for secretion of Dengue and Zika infectious particles and their corresponding virus like particles (VLPs). Pharmacological inhibition or genetic depletion of the SFKs, Lyn in particular, block virus secretion. Lyn−/− cells are impaired in virus release and are rescued when reconstituted with wild-type Lyn, but not a kinase- or palmitoylation-deficient Lyn mutant. We establish that virus particles are secreted in two distinct populations – one as free virions and the other enclosed within membranes. Lyn is critical for the latter, which consists of proteolytically processed, infectious virus progenies within autophagosome-derived vesicles. This process depends on Ulk1, Rab GTPases and SNARE complexes implicated in secretory but not degradative autophagy and occur with significantly faster kinetics than the conventional secretory pathway. Our study reveals a previously undiscovered Lyn-dependent exit route of flaviviruses in LC3+ secretory organelles that enables them to evade circulating antibodies and might affect tissue tropism.
We use photorefractive two-wave mixing for coherent amplification of the object beam in digital holographic recording. Both amplitude and phase reconstruction benefit from the prior amplification as they have an increased SNR. We experimentally verify that the amplification process does not affect the phase of the wavefield. This allows for digital holographic phase analysis after amplification. As the grating formation in photorefractive crystals is just driven by coherent light, the crystal works as a coherence gate. Thus the proposed combination allows for applying digital holography for imaging through scattering media, after the image bearing light is coherence gated and filtered out of scattered background. We show experimental proof-of principle results.
No abstract
The vehicular ad hoc network (VANET) has made significant progress in recent years, attracting a lot of interest from academia and the industry. VANET involves vehicle-to-vehicle (V2V) and vehicle-to-infrastructure (V2I) communications based on a wireless network. V2I refers to the communication between vehicles and infrastructure of roadside unit (RSU), e.g., a base station and access point (AP) connected to the Internet. V2V refers to the direct or multi-hop communications among vehicles in VANET. V2V is efficient and cost effective owing to its short range bandwidth advantage and its ad hoc nature. V2V communications are enabling technologies that enhance the driver’s awareness of nearby vehicular traffic, leading to improved traffic safety and efficiency. The V2V mode provides a communications platform between road vehicles (cars, bikes, scooters, motorcycles, trucks, etc.) without requiring a central control unit. Safety-related V2V applications are enabled via an integrated early warning mechanism. To facilitate safe driving, we propose an Intelligent Vehicular Warning System (IVWS) that sends an immediate warning message in the event of an accident. According to V2V communications, the other cars or vehicles could have enough time to avoid the accident and make an appropriate decision such as slow down, stop, and detour after receiving the urgent warning messages. Furthermore, the local CMS (Changeable Message Sign) can show the accident information for neighbor vehicles when receiving the warning message. To achieve experimental architecture with our proposed IVWS, the robot vehicles have been designed to simulate vehicles on the road. Besides, vehicles also apply ZigBee wireless interface to communicate with each other. The experiment has shown that our proposed intelligent system can initially provide message display and safety driving for vehicles when traffic accident occurred.
Pickle is normally served as a side dish with the main meal or used as an appetizer and also favored by many Chinese. However, the accumulation of nitrite is a common problem faced during many vegetables fermentations. Effects of different fermentation conditions on the nitrite concentration were investigated during the preparation of lactobacillus pickles by using the modern biological technology. The results showed that the salt, lactobacillus preparation and some accessories could reduce the nitrite content during the carrot-pickles fermentation, and improve the safety of lactobacillus preparation pickles.
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