Publications by authors named "B Cubitt"
Article Synopsis
- - Lassa virus (LASV) leads to hundreds of thousands of infections in Western Africa annually, with about 20% progressing to Lassa fever, a serious disease that has a high fatality rate.
- - Currently, there are no approved vaccines or treatments for Lassa fever, but researchers have been working on recombinant LASVs (rLASVs) that show promising results as vaccines in animal models.
- - The new vaccine candidate, rLASV/IGR-CD, demonstrated high safety and effectiveness in guinea pigs, offering complete protection against lethal LASV exposure and advancing the development of a live-attenuated vaccine for Lassa fever.
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.
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- - The Z protein of mammarenaviruses is crucial for virus assembly and exiting host cells, while glycoproteins GP1 and GP2, linked by a stable signal peptide, form spikes that help the virus enter host cells.
- - Myristoylation, a modification performed by host cell enzymes, is essential for the function of both the Z protein and the stable signal peptide, with mutations that block this process negatively impacting virus budding and fusion.
- - The study reveals that the NMT inhibitor DDD85464 shows strong antiviral effects against various mammarenaviruses, including LCMV, JUNV, and LASV, by disrupting Z protein activity and reducing viral entry processes.
Many viruses, including mammarenaviruses, have evolved mechanisms to counteract different components of the host cell innate immunity, which is required to facilitate robust virus multiplication. The double-stranded RNA (dsRNA) sensor protein kinase receptor (PKR) pathway plays a critical role in the cell anti-viral response. Whether PKR can restrict the multiplication of the Old World mammarenavirus lymphocytic choriomeningitis virus (LCMV) and the mechanisms by which LCMV may counteract the anti-viral functions of PKR have not yet been investigated.
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- CD8 T cell memory usually needs CD4 T cell help, but in some cases, like quickly resolving viral infections, CD8 T cells can develop without it, though they struggle to respond to future infections.
- The study shows that while helpless CD8 T cells form normally, they have defects in memory maturation due to prolonged exposure to antigens, which negatively affects their response to pathogens.
- Over time, these memory defects improve, restoring the CD8 T cells’ full capabilities, highlighting their adaptability and suggesting new strategies for vaccines and immunology.