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Castaneda Copeland posted an update 6 months, 3 weeks ago
Childhood immunization with the live-attenuated varicella zoster virus (VZV) vaccine induces protective immune responses. Routine VZV vaccination started only two decades ago and thus there are few studies examining the longevity of vaccine-induced immunity. Herein, we analyzed the quantity of VZV-specific plasma cells (PCs) and CD4 T cells in the bone marrow (BM) of healthy young adults (n=15) following childhood VZV immunization. Long-lived BM resident plasma cells constitutively secrete antibodies and we detected VZV-specific PCs in the BM of all subjects. Anti-VZV plasma antibody titers correlated positively with the number of VZV-specific BM PCs. Furthermore, we quantified the number of IFNγ-producing CD4 T cells specific for VZV glycoprotein E and all other structural and non-structural VZV proteins in both BM and blood (PBMCs). The frequency of VZV-specific IFNγ-producing CD4 T cells was significantly higher in PBMCs compared to BM. Our study shows that VZV-specific PCs and VZV-specific CD4 memory T cells persist up to 20 years after vaccination. These findings indicate that childhood VZV vaccination can elicit long-lived immune memory responses in the bone marrow.IMPORTANCE Childhood varicella zoster virus (VZV) immunization induces immune memory responses that protect against primary VZV infection, chickenpox. In the US, routine childhood VZV vaccination has been introduced only two decades ago. Hence, there is limited information on the longevity of B and CD4 T cell memory which are both important for protection. Here we show in fifteen healthy young adults that VZV-specific B and CD4 T cell responses are detectable in bone marrow (BM) and blood up to 20 years after vaccination. Specifically, we measured antibody-secreting plasma cells in the BM and VZV-specific CD4 T cells in BM and blood. These findings suggest that childhood VZV vaccination induces long-lived immunity. Copyright © 2020 American Society for Microbiology.Human norovirus frequently causes outbreaks of acute gastroenteritis. Although discovered more than five decades ago, antiviral development has, until recently, been hampered by the lack of a reliable human norovirus cell culture system. Nevertheless, a lot of pathogenesis studies were accomplished using murine norovirus (MNV), which can be grown routinely in cell culture. In this study, we analysed a sizeable library of Nanobodies that were raised against the murine norovirus virion with the main purpose of developing Nanobody-based inhibitors. We discovered two types of neutralizing Nanobodies and analysed the inhibition mechanisms using X-ray crystallography, cryo-EM, and cell culture techniques. The first type bound on the top region of the protruding (P) domain. Interestingly, the Nanobody binding region closely overlapped the MNV receptor-binding site and collectively shared numerous P domain-binding residues. In addition, we showed that these Nanobodies competed with the soluble receptor and this actioal replication. In fact, the capsid appeared to be organized in a state of flux, which could be important for co-factor/receptor binding functions. Blocking these capsid-binding events with Nanobodies directly inhibited essential capsid functions. Moreover, a number of MNV-specific Nanobody binding epitopes were comparable to human norovirus-specific Nanobody inhibitors. Therefore, this additional structural and inhibition information could be further exploited in the development of human norovirus antivirals. Copyright © 2020 American Society for Microbiology.Highly pathogenic avian influenza (HPAI) viruses are enzootic in wild birds and poultry and continue to cause human infections with high mortality. To date, more than 850 confirmed human cases of H5N1 virus infection have been reported, of which ∼60% were fatal. Global concern persists that these or similar avian influenza viruses will evolve into viruses that can transmit efficiently between humans, causing a severe influenza pandemic. It was shown previously that a change in receptor specificity is a hallmark for adaptation to humans and evolution towards a transmittable virus.Substantial genetic diversity was detected within the receptor binding site of hemagglutinin of HPAI A/H5N1 viruses, evolved during human infection, as detected by next generation sequencing. Here we investigated the functional impact of substitutions that were detected during these human infections. Upon rescue of 21 mutant viruses, most substitutions in the RBS resulted in viable virus, but virus replication, entry and stability werly in a diverse set of assays, including virus replication, stability and receptor specificity. None of the tested substitutions resulted in a clear step towards a human adapted virus capable of aerosol transmission. It is notable that acquiring human-type receptor specificity needs multiple amino acid mutations, and that variability at key position 226 is not tolerated, reducing the risk of them being acquired naturally. Copyright © 2020 American Society for Microbiology.Low pathogenic avian influenza viruses (LPAIVs) are genetically highly variable and have diversified into multiple evolutionary lineages that are primarily associated with wild bird reservoirs. Antigenic variation has been described for mammalian influenza viruses and for highly pathogenic avian influenza viruses that circulate in poultry, but much less is known about antigenic variation of LPAIVs. In this study, we focussed on H13 and H16 LPAIVs that circulate globally in gulls. We investigated the evolutionary history and intercontinental gene flow based on the hemagglutinin (HA) gene and used representative viruses from genetically distinct lineages to determine their antigenic properties by hemagglutination inhibition assays. For H13 at least three distinct genetic clades were evident, while for H16 at least two distinct genetic clades were evident. Twenty and ten events of intercontinental gene flow were identified for H13 and for H16 viruses, respectively. At least two antigenic variants of H13 and at ltercontinental gene flow, and the antigenic variation among H13 and H16 LPAIVs. The circulation of the subtypes H13 and H16 seems to be maintained by a narrower host range, in particular gulls, than for the majority of LPAIV subtypes and may therefore serve as a model for evolution and epidemiology of H1-H12 LPAIVs in wild birds. Selleck RGD (Arg-Gly-Asp) Peptides The findings suggest that H13 and H16 LPAIVs circulate independently of each other and emphasize the need to investigate within clade antigenic variation of LPAIVs in wild birds. Copyright © 2020 Verhagen et al.
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