University of Amsterdam

About: University of Amsterdam is a education organization based out in Amsterdam, Noord-Holland, Netherlands. It is known for research contribution in the topics: Population & Context (language use). The organization has 59309 authors who have published 140894 publications receiving 5984137 citations. The organization is also known as: UvA & Universiteit van Amsterdam.

Human coronavirus NL63 employs the severe acute respiratory syndrome coronavirus receptor for cellular entry

Abstract: Coronavirus (CoV) infection of humans is usually not associated with severe disease. However, discovery of the severe acute respiratory syndrome (SARS) CoV revealed that highly pathogenic human CoVs (HCoVs) can evolve. The identification and characterization of new HCoVs is, therefore, an important task. Recently, a HCoV termed NL63 was discovered in patients with respiratory tract illness. Here, cell tropism and receptor usage of HCoV-NL63 were analyzed. The NL63 spike (S) protein mediated infection of different target cells compared with the closely related 229E-S protein but facilitated entry into cells known to be permissive to SARS-CoV-S-driven infection. An analysis of receptor engagement revealed that NL63-S binds angiotensin-converting enzyme (ACE) 2, the receptor for SARS-CoV, and HCoV-NL63 uses ACE2 as a receptor for infection of target cells. Potent neutralizing activity directed against NL63- but not 229E-S protein was detected in virtually all sera from patients 8 years of age or older, suggesting that HCoV-NL63 infection of humans is common and usually acquired during childhood. Here, we show that SARS-CoV shares its receptor ACE2 with HCoV-NL63. Because the two viruses differ dramatically in their ability to induce disease, analysis of HCoV-NL63 might unravel pathogenicity factors in SARS-CoV. The frequent HCoV-NL63 infection of humans suggests that highly pathogenic variants have ample opportunity to evolve, underlining the need for vaccines against HCoVs.

Cryo-EM Structure of a Fully Glycosylated Soluble Cleaved HIV-1 Envelope Trimer

Abstract: The HIV-1 envelope glycoprotein (Env) trimer contains the receptor binding sites and membrane fusion machinery that introduce the viral genome into the host cell. As the only target for broadly neutralizing antibodies (bnAbs), Env is a focus for rational vaccine design. We present a cryo-electron microscopy reconstruction and structural model of a cleaved, soluble SOSIP gp140 trimer in complex with a CD4 binding site (CD4bs) bnAb, PGV04, at 5.8 A resolution. The structure reveals the spatial arrangement of Env components, including the V1/V2, V3, HR1 and HR2 domains, and shielding glycans. The structure also provides insights into trimer assembly, gp120-gp41 interactions, and the CD4bs epitope cluster for bnAbs, which covers a more extensive area and defines a more complex site of vulnerability than previously described.

Maternal-fetal transfer of thyroxine in congenital hypothyroidism due to a total organification defect or thyroid agenesis.

Abstract: The fact that neonates who subsequently have severe hypothyroidism have no evidence of the condition at birth suggests the possibility of the placental transfer of thyroid hormones. Recent studies have demonstrated the existence of such transfer in hypothyroid rats. To determine whether there is a transfer of thyroxine (T4) from mother to fetus, we studied 25 neonates born with a complete inability to iodinate thyroid proteins and therefore to synthesize T4. This total organification defect is an autosomal recessive disorder with an incidence of approximately 1 in 60,000 neonates in the Netherlands. In the cord serum of affected neonates, T4 levels ranged from 35 to 70 nmol per liter. Since these patients were unable to produce any T4, the T4 must have originated in their mothers. The estimated biologic half-life of serum T4 was 3.6 days (95 percent confidence interval, 2.7 to 5.3). In 15 neonates with thyroid agenesis, the serum levels and the disappearance kinetics of T4 were the same as those in the neonates with a total organification defect, suggesting that in these infants, the T4 also had a maternal origin. We conclude that in infants with severe congenital hypothyroidism, substantial amounts of T4 are transferred from mother to fetus during late gestation.