The NS2B-PP1α-eIF2α axis: Inhibiting stress granule formation and Boosting Zika virus replication.

Stress granules (SGs), formed by untranslated messenger ribonucleoproteins (mRNPs) during cellular stress in eukaryotes, have been linked to flavivirus interference without clear understanding. This study reveals the role of Zika virus (ZIKV) NS2B as a scaffold protein mediating interaction between protein phosphatase 1α (PP1α) and eukaryotic initiation factor 2α (eIF2α). This interaction promotes eIF2α dephosphorylation by PP1α, inhibiting SG formation. The NS2B-PP1α complex exhibits remarkable stability, resisting ubiquitin-induced degradation and amplifying eIF2α dephosphorylation, thus promoting ZIKV replication. In contrast, the NS2BV35A mutant, interacting exclusively with eIF2α, fails to inhibit SG formation, resulting in reduced viral replication and diminished impact on brain organoid growth. These findings reveal PP1α's dual role in ZIKV infection, inducing interferon production as an antiviral factor and suppressing SG formation as a viral promoter. Moreover, we found that NS2B also serves as a versatile mechanism employed by flaviviruses to counter host antiviral defenses, primarily by broadly inhibiting SG formation. This research advances our comprehension of the complex interplay in flavivirus-host interactions, offering potential for innovative therapeutic strategies against flavivirus infections.

SASFF: A Video Synthesis Algorithm for Unstructured Array Cameras Based on Symmetric Auto-Encoding and Scale Feature Fusion.

For the synthesis of ultra-large scene and ultra-high resolution videos, in order to obtain high-quality large-scene videos, high-quality video stitching and fusion are achieved through multi-scale unstructured array cameras. This paper proposes a network model image feature point extraction algorithm based on symmetric auto-encoding and scale feature fusion. By using the principle of symmetric auto-encoding, the hierarchical restoration of image feature location information is incorporated into the corresponding scale feature, along with deep separable convolution image feature extraction, which not only improves the performance of feature point detection but also significantly reduces the computational complexity of the network model. Based on the calculated high-precision feature point pairing information, a new image localization method is proposed based on area ratio and homography matrix scaling, which improves the speed and accuracy of the array camera image scale alignment and positioning, realizes high-definition perception of local details in large scenes, and obtains clearer synthesis effects of large scenes and high-quality stitched images. The experimental results show that the feature point extraction algorithm proposed in this paper has been experimentally compared with four typical algorithms using the HPatches dataset. The performance of feature point detection has been improved by an average of 4.9%, the performance of homography estimation has been improved by an average of 2.5%, the amount of computation has been reduced by 18%, the number of network model parameters has been reduced by 47%, and the synthesis of billion-pixel videos has been achieved, demonstrating practicality and robustness.

P300-mediated NEDD4 acetylation drives ebolavirus VP40 egress by enhancing NEDD4 ligase activity.

The final stage of Ebola virus (EBOV) replication is budding from host cells, where the matrix protein VP40 is essential for driving this process. Many post-translational modifications such as ubiquitination are involved in VP40 egress, but acetylation has not been studied yet. Here, we characterize NEDD4 is acetylated at a conserved Lys667 mediated by the acetyltransferase P300 which drives VP40 egress process. Importantly, P300-mediated NEDD4 acetylation promotes NEDD4-VP40 interaction which enhances NEDD4 E3 ligase activity and is essential for the activation of VP40 ubiquitination and subsequent egress. Finally, we find that Zaire ebolavirus production is dramatically reduced in P300 knockout cell lines, suggesting that P300-mediated NEDD4 acetylation may have a physiological effect on Ebola virus life cycle. Thus, our study identifies an acetylation-dependent regulatory mechanism that governs VP40 ubiquitination and provides insights into how acetylation controls EBOV VP40 egress.

Viral strategies for triggering and manipulating mitophagy.

Viral infection causes many physiological alterations in the host cell, and many of these alterations can affect the host mitochondrial network, including mitophagy induction. A substantial amount of literature has been generated that advances our understanding of the relationship between mitophagy and several viruses. Some viruses trigger mitophagy directly, and indirectly and control the mitophagic process via different strategies. This enables viruses to promote persistent infection and attenuate the innate immune responses. In this review, we discuss the events of virus-regulated mitophagy and the functional relevance of mitophagy in the pathogenesis of viral infection and disease. Abbreviation: ATG: autophagy related; BCL2L13: BCL2 like 13; BNIP3L/NIX: BCL2 interacting protein 3 like; CL: cardiolipin; CSFV: classical swine fever virus; CVB: coxsackievirus B; DENV: dengue virus; DNM1L: dynamin 1 like; FIS1: fission, mitochondrial 1; FUNDC1: FUN14 domain containing 1; HPIV3: human parainfluenza virus 3; HSV-1: herpes simplex virus type 1; IMM: inner mitochondrial membrane; IAV: influenza A virus; IFN: interferon; IKBKE/IKKε: inhibitor of nuclear factor kappa B kinase subunit epsilon; LUBAC: linear ubiquitin assembly complex; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MeV: measles virus; MAVS: mitochondrial antiviral signaling protein; MFF: mitochondria fission factor; NLRP3: NLR family pyrin domain containing 3; NDV: Newcastle disease virus; NR4A1: nuclear receptor subfamily 4 group A member 1; OMM: outer mitochondrial membrane; OPA1: OPA1, mitochondrial dynamin like GTPase; PRKN: parkin RBR E3 ubiquitin protein ligase; PINK1: PTEN induced putative kinase 1; PHB2: prohibitin 2; PRRSV: porcine reproductive and respiratory syndrome virus; PRRs: pattern-recognition receptors; RLRs: RIG-I-like receptors; ROS: reactive oxygen species; RIPK2: receptor interacting serine/threonine kinase 2; SESN2: sestrin 2; SNAP29: synaptosome associated protein 29; STX17: syntaxin 17; TGEV: transmissible gastroenteritis virus; TUFM: Tu translation elongation factor, mitochondrial; TRAF2: TNF receptor associated factor 2; TRIM6: tripartite motif containing 6; Ub: ubiquitin; ULK1: unc-51 like autophagy activating kinase 1; VZV: varicella-zoster virus.

The Matrix Protein of Human Parainfluenza Virus Type 3 Induces Mitophagy that Suppresses Interferon Responses.

Mitophagy is a form of autophagy that selectively removes damaged mitochondria. Impaired mitochondria can be tagged by the kinase PINK1, which triggers recruitment of the E3-ubiquitin ligase Parkin and subsequent mitochondrial sequestration within autophagosomes. We previously found that human parainfluenza virus type 3 (HPIV3) infection induces autophagy, but the type and mechanisms of autophagy induction remain unknown. Here, we show that matrix protein (M) of HPIV3 translocates to mitochondria and interacts with Tu translation elongation factor mitochondrial (TUFM). M-mediated mitophagy does not require the Parkin-PINK1 pathway but rather an interaction between M and the LC3 protein that mediates autophagosome formation. These interactions with both TUFM and LC3 are required for the induction of mitophagy and lead to inhibition of the type I interferon response. These results reveal that a viral protein is sufficient to induce mitophagy by bridging autophagosomes and mitochondria.