Mutation for microcephaly: Zika virus infections in humans have been known since 1947. Microcephaly and neuropathologies associated with Zika have only been reported recently, most prevalently in the Americas. Yuan et al. investigated recent stable mutations in the virus genome and engineered them into a low-virulence ancestral strain (see the Perspective by Screaton and Mongkolsapaya). A single amino acid substitution (serine to asparagine, S139N) in the viral precursor membrane protein exacerbated symptoms in pregnant mice. The reverse mutation (N139S) was less virulent. The S139N mutation arose in 2013 in French Polynesia before the virus jumped to Brazil in 2015. In vitro, this amino acid change made the virus more infectious for mouse and human neural progenitor cells and promoted apoptosis. The terrible sequelae of infection during pregnancy could thus be the result of a simple viral mutation. Science , this issue p. 933 ; see also p. 863

Animal models are critical to understand disease and to develop countermeasures for the ongoing epidemics of Zika virus (ZIKV). Here we report a non-human primate model using a 2016 contemporary clinical isolate of ZIKV. Upon subcutaneous inoculation, rhesus macaques developed fever and viremia, with robust excretion of ZIKV RNA in urine, saliva, and lacrimal fluid. Necropsy of two infected animals revealed that systematic infections involving central nervous system and visceral organs were established at the acute phrase. ZIKV initially targeted the intestinal tracts, spleen, and parotid glands, and retained in spleen and lymph nodes till 10days post infection. ZIKV-specific immune responses were readily induced in all inoculated animals. The non-human primate model described here provides a valuable platform to study ZIKV pathogenesis and to evaluate vaccine and therapeutics.

Both the endothelial transporter Mfsd2a and docosahexaenoic acid uptake are disrupted in Zika virus–induced microcephaly models.

Zika virus (ZIKV) has evolved from an overlooked mosquito-borne flavivirus into a global health threat due to its astonishing causal link to microcephaly and other disorders. ZIKV has been shown to infect neuronal progenitor cells of the fetal mouse brain, which is comparable to the first-trimester human fetal brain, and result in microcephaly. However, whether there are different effects between the contemporary ZIKV strain and its ancestral strain in the neonatal mouse brain, which is comparable with the second-trimester human fetal brain, is unclear. Here we adopted a mouse model which enables us to study the postnatal effect of ZIKV infection. We show that even 100 pfu of ZIKV can replicate and infect neurons and oligodendrocytes in most parts of the brain. Compared with the ancestral strain from Cambodia (CAM/2010), infection of the ZIKV strain from Venezuela (VEN/2016) leads to much more severe microcephaly, accompanied by more neuronal cell death, abolishment of oligodendrocyte development, and a more dramatic immune response. The serious brain damage caused by VEN/2016 infection would be helpful to elucidate why the American strain resulted in severe neurovirulence in infants and will provide clinical guidance for the diagnosis and treatment of infection by different ZIKV strains.

Combining magnetic particle spectroscopy (MPS) with functionalized magnetic nanoparticles (MNPs) has the potential to provide a rapid, sensitive, and user-friendly point-of-care testing platform. Conventional MPS techniques typically apply harmonic ratios (such as, third to fifth harmonic ratio) as the sensing metric to eliminate interference caused by MNP concentration. However, the quantification accuracy of this approach largely depends on the consistency of the signal-to-noise ratio between the selected harmonics, imposing stringent requirements on hardware design and the nonlinear magnetic behavior of the MNPs. In this study, we introduce "peak shift" to field-swept magnetic particle spectroscopy (FS-MPS) as a novel metric for MNP characterization and biosensing. An integrated FS-MPS device is used to capture the second harmonic spectrum, which records the second harmonic amplitudes under different perpendicular static magnetic fields. Importantly, the peak position of the spectrum remains constant under different MNP concentrations and shifts upon changes in MNP hydrodynamic size. In this way, the peak shift sensitively detects MNP binding to the targeted analytes, enabling robust biosensing based solely on the second harmonics. The feasibility of the proposed method was demonstrated using streptavidin-grafted MNPs and biotinylated polystyrene beads. Diagnostic performance was assessed using ACE2 functionalized MNPs and SARS-CoV-2 S1 protein and SARS-CoV-2 pseudovirus assays. The proposed strategy can detect virus concentrations as low as 350 TCID ₅₀ /mL. Additionally, a good linear correlation exists between the peak shift and virus titer in the 350–7000 TCID ₅₀ /mL range, demonstrating the potential of our method to quantify virus content.