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Order Tymovirales
Published in Paul Pumpens, Peter Pushko, Philippe Le Mercier, Virus-Like Particles, 2022
Paul Pumpens, Peter Pushko, Philippe Le Mercier
The VLP story of another remarkable member of the Potexvirus genus, papaya mosaic virus (PapMV), was started with the successful disassembly and reassembly of viral particles in vitro (Erickson et al. 1976), where the PapMV coat was prepared by the classical acetic acid degradation of purified virus (Fraenkel-Conrat 1957) and reconstituted into nucleocapsid-like structures in the absence of RNA. The aggregates ranged from 14S to 25S where 14S was a helical disk-like structure of 18–20 subunits (Erickson and Bancroft 1978; Erickson et al. 1978). These disks were the structures of two turns of the helix and were similar in architecture to the native virus particle elements (Erickson et al. 1976, 1983). The addition of RNA (Erickson et al. 1976) or single-stranded DNA (Erickson and Bancroft 1980) to the isolated disks triggered the assembly of the long rod-shaped particles similar to the original virions.
Mechanisms of cellular and humoral immunity through the lens of VLP-based vaccines
Published in Expert Review of Vaccines, 2022
Hunter McFall-Boegeman, Xuefei Huang
Which of the three aforementioned pathways dominates is up for debate, as is which pathway is important for antigens delivered by VLP-based vaccines[112,121]. There is very little work discussing cross-presentation of antigens delivered by VLPs. The scant information indicates the results may depend on the VLP utilized. Work from Win et al. suggests it is through endosomal recycling of MHC class I molecules, by exploring cross-presentation of ovalbumin (OVA) and human melanoma-associated antigen (MART-1) delivered by rabbit hemorrhagic disease virus (RHDV)-based VLPs[87]. To study cross-presentation, inhibitors of specific pathways were utilized, which include lactacystin to inhibit proteasomal processing, US6 to prevent TAP-mediated transport, brefeldin A to inhibit vesicle secretion, bafilomycin A1 to prevent phagolysosome acidification, and primaquine to inhibit recycling of cell surface molecules. The final three inhibitors act at different stages of endosomal recycling pathway and virtually erased cross-presentation as measured by activation of antigen-specific CD8+ T cells. This was in direct contradiction to when soluble antigens were used. With soluble antigens, each inhibitor had some effects on the activation efficiency but did not completely abolish cross-presentation. This suggests that conjugation to VLPs shifted the importance of cross-presentation pathways to the endosomal recycling pathway. This was further supported by earlier work by Leclerc et. al. who used a similar lactacytsin based experiment to rule out proteasomal processing of antigens delivered by Papaya Mosaic Virus (PapMV) VLPs[122]. On the other hand, porcine parvovirus (PPV) VLPs loaded with OVA CTLes were cross-presented in a TAP and proteasome dependent, endosome-to-cytosol pathway[86]. Between the two extremes is the evidence provided by Ruedl et. al. They showed that DCs in TAP-deficient mice exhibited decreased cross-presentation efficiency compared to wild type mice when treated with Hepatitis B core antigen (HBcAg) VLPs but still retained the ability to activate potent T cell responses[123]. While each study used different sets of antigens overall, there were enough overlaps to suggest the different cross-presentation fates were likely due to the VLPs used in the studies. Taken together, these results indicate that the VLPs are biasing cross-presentation toward a certain pathway, but the exact mechanism is unknown. Size might be a determining factor as microspheres displayed size-dependent changes to cross-presentation efficiency when the proteosome was inhibited[124]. However, the smallest microspheres (d = 800 nm) examined are the size of some of the largest VLPs known. This suggests that the differences described above are likely due to more than just size, as the RHDV (d = 32–44 nm), PPV (d = 25–30 nm), and HBcAg (d = 29.4 nm) VLPs are an order of magnitude smaller than the microspheres[125–128].