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We report that the lymphocytic choriomeningitis virus (LCMV) matrix protein, which drives viral budding, is phosphorylated at serine 41 (S41). A recombinant (r)LCMV bearing a phosphomimetic mutation (S41D) was impaired in infectious and defective interfering (DI) particle release, while a non-phosphorylatable mutant (S41A) was not. The S41D mutant was disproportionately impaired in its ability to release DI particles relative to infectious particles. Thus, DI particle production by LCMV may be dynamically regulated via phosphorylation of S41.
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http://dx.doi.org/10.1099/jgv.0.000550 | DOI Listing |
Biochem (Basel)
June 2025
Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Background/objectives: N-Myristoyltransferase inhibitors (NMTi) represent a novel antiviral strategy against mammarenaviruses such as Lassa and Junin viruses. The Z matrix protein inhibits viral ribonucleoprotein (vRNP) activity in a dose-dependent manner. Here, we investigated whether Z-mediated vRNP inhibition depends on Z myristoylation or oligomerization.
View Article and Find Full Text PDFFront Immunol
April 2025
Syngene International Limited, Bengaluru, India.
In solid tumors, the tumor microenvironment (TME) is a complex mix of tumor, immune, stromal cells, fibroblasts, and the extracellular matrix. Cytotoxic T lymphocytes (CTLs) constitute a fraction of immune cells that may infiltrate into the TME. The primary function of these T-cells is to detect and eliminate tumor cells.
View Article and Find Full Text PDFFront Neurosci
March 2025
Department of Biomedical Engineering, Tehran University of Medical Sciences, Tehran, Iran.
This paper illustrates the development of two efficient source localization algorithms for electroencephalography (EEG) data, aimed at enhancing real-time brain signal reconstruction while addressing the computational challenges of traditional methods. Accurate EEG source localization is crucial for applications in cognitive neuroscience, neurorehabilitation, and brain-computer interfaces (BCIs). To make significant progress toward precise source orientation detection and improved signal reconstruction, we introduce the Accelerated Linear Constrained Minimum Variance (ALCMV) beamforming toolbox and the Accelerated Brain Source Orientation Detection (AORI) toolbox.
View Article and Find Full Text PDFViruses
August 2024
Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
The mammarenavirus matrix Z protein plays critical roles in virus assembly and cell egress. Meanwhile, heterotrimer complexes of a stable signal peptide (SSP) together with glycoprotein subunits GP1 and GP2, generated via co-and post-translational processing of the surface glycoprotein precursor GPC, form the spikes that decorate the virion surface and mediate virus cell entry via receptor-mediated endocytosis. The Z protein and the SSP undergo N-terminal myristoylation by host cell N-myristoyltransferases (NMT1 and NMT2), and G2A mutations that prevent myristoylation of Z or SSP have been shown to affect the Z-mediated virus budding and GP2-mediated fusion activity that is required to complete the virus cell entry process.
View Article and Find Full Text PDFJ Virol
October 2024
California NanoSystems Institute, University of California, Los Angeles, California, USA.
Unlabelled: Arenaviruses exist globally and can cause hemorrhagic fever and neurological diseases, exemplified by the zoonotic pathogen lymphocytic choriomeningitis virus (LCMV). The structures of individual LCMV proteins or their fragments have been reported, but the architectural organization and the nucleocapsid assembly mechanism remain elusive. Importantly, the structure of the arenavirus fusion protein complex (glycoprotein complex, GPC) as present on the virion prior to fusion, particularly with its integral stable signal peptide (SSP), has not been shown, hindering efforts such as structure-based vaccine design.
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