Structures of flavivirus (dengue virus and Zika virus) particles are known to near-atomic resolution and show detailed structure and arrangement of their surface proteins (E and prM in immature virus or M in mature virus). By contrast, the arrangement of the capsid proteins: RNA complex, which forms the core of the particle, is poorly understood, likely due to inherent dynamics. Here, we stabilize immature Zika virus via an antibody that binds across the E and prM proteins, resulting in a subnanometer resolution structure of capsid proteins within the virus particle. Fitting of the capsid protein into densities shows the presence of a helix previously thought to be removed via proteolysis. This structure illuminates capsid protein quaternary organization, including its orientation relative to the lipid membrane and the genomic RNA, and its interactions with the transmembrane regions of the surface proteins. Results show the capsid protein plays a central role in the flavivirus assembly process.

The rapid spread of Zika virus (ZIKV), which causes microcephaly and Guillain-Barré syndrome, signals an urgency to identify therapeutics. Recent efforts to rescreen dengue virus human antibodies for ZIKV cross-neutralization activity showed antibody C10 as one of the most potent. To investigate the ability of the antibody to block fusion, we determined the cryoEM structures of the C10-ZIKV complex at pH levels mimicking the extracellular (pH8.0), early (pH6.5) and late endosomal (pH5.0) environments. The 4.0 Å resolution pH8.0 complex structure shows that the antibody binds to E proteins residues at the intra-dimer interface, and the virus quaternary structure-dependent inter-dimer and inter-raft interfaces. At pH6.5, antibody C10 locks all virus surface E proteins, and at pH5.0, it locks the E protein raft structure, suggesting that it prevents the structural rearrangement of the E proteins during the fusion event—a vital step for infection. This suggests antibody C10 could be a good therapeutic candidate.

INTRODUCTION Fertility in women declines with increasing age. With the deferment of marriage and childbearing, couples are turning to assisted reproductive technology to counteract this decline. We aimed to evaluate the results of in vitro fertilisation (IVF)/intracytoplasmic sperm injection (ICSI) in women of different age groups, and highlight the cost-effectiveness of IVF treatment in these groups while assessing its implications on the national healthcare provision model. METHODS RESULTSAge had a significant effect on the number of cycles leading to embryo transfer (p < 0.001). The number of oocytes retrieved decreased across the various age groups (p < 0.001) and was the highest among women aged < 30 (mean 18.5 ± 10.3) years. With increasing age, there was a trend toward a lower fertilisation rate. Age also had a significant effect on the rates of clinical pregnancy, live birth and multiple pregnancies (p < 0.001). CONCLUSIONPatients aged < 30 years had the best IVF outcomes, reflecting optimal reproductive capacity. Age-related decline in fertility starts after 30 years. Women opting for IVF should be counselled about age-specific success rates while taking into account individual risk factors.

Dengue virus (DENV) infection affects millions of people annually and has the potential to cause fatal haemorrhagic fever and shock. Although the underlying pathogenesis of severe dengue illness is still unclear, current evidence suggests that severe disease progression has an immunological basis. In this study, we investigated the role of caspase-1 during host-pathogen interactions within DENV-infected human monocytes. Using DENV-infected primary monocytes, we examined caspase-1 at various levels of gene expression and probed for potential immune consequences mediated by caspase-1 such as secretion of pro-inflammatory IL-1β and pyroptotic cell death. We report that DENV-infected monocytes upregulated functional caspase-1 mRNA and pro-caspase-1 activation as a late response to infection. In addition, we found that caspase-1 is responsible for IL-1β secretion and pyroptosis of DENV-infected monocytes. Together, our results show that late caspase-1 activation within DENV-infected monocytes can contribute to pro-inflammatory outcomes that might play a role in dengue immunopathogenesis.