A broadly protective human antibody for GI genogroup noroviruses.

Noroviruses infect millions each year, and while effective countermeasures are eagerly sought, none have been reported for the GI genogroup, first described more than 50 years ago. Here, to provide insight into GI norovirus neutralization, we isolated a broad GI antibody, 16E10, from a human blood donor and showed it neutralizes noroviruses in human enteroid cultures and abrogates or reduces infection in rhesus macaques. The cryogenic electron microscopy reconstruction of 16E10 with a norovirus protruding-domain dimer at 2.

Cytotoxic Signature and IFN-γ Production Dominate CD4 T-Cell Response During Human Toxoplasmosis.

Toxoplasma gondii is a highly versatile parasite that infects most warm-blooded animals and is a major cause of retinochoroiditis and uveitis in humans. The pathophysiology of these conditions remains poorly understood. Both parasite virulence and host inflammatory response contribute to the development of ocular disease.

Signatures of CD4 T and B cells are associated with distinct stages of chronic chagasic cardiomyopathy.

Introduction: Chagas disease is a neglected parasitic disease caused by . While most patients are asymptomatic, around 30% develop Chronic Chagasic Cardiomyopathy (CCC).

Methods: Here, we employed high-dimensional flow cytometry to analyze CD4 T and B cell compartments in patients during the chronic phase of Chagas disease, presenting the asymptomatic and mild or moderate/severe cardiac clinical forms.

N-glycoproteomic analyses of human intestinal enteroids, varying in histo-blood group geno- and phenotypes, reveal a wide repertoire of fucosylated glycoproteins.

Human noroviruses, globally the main cause of viral gastroenteritis, show strain specific affinity for histo-blood group antigens (HBGA) and can successfully be propagated ex vivo in human intestinal enteroids (HIEs). HIEs established from jejunal stem cells of individuals with different ABO, Lewis and secretor geno- and phenotypes, show varying susceptibility to such infections. Using bottom-up glycoproteomic approaches we have defined and compared the N-linked glycans of glycoproteins of seven jejunal HIEs.

A non-human primate model for human norovirus infection.

Norovirus infection can cause gastrointestinal disease in humans. Development of therapies and vaccines against norovirus have been limited by the lack of a suitable and reliable animal model. Here we established rhesus macaques as an animal model for human norovirus infection.

Chagasic cardiomyopathy is marked by a unique signature of activated CD4 T cells.

Chagas disease is a neglected tropical disease in Latin America and an imported emerging disease worldwide. Chronic Chagas disease cardiomyopathy (CCC) is the most prominent clinical form and can lead to heart failure, thromboembolism, and sudden death. While previous reports have supported a role for CD4 T lymphocytes in the pathogenesis of CCC a comprehensive analysis of these cells during different clinical forms is lacking.

Histo-blood group antigens of glycosphingolipids predict susceptibility of human intestinal enteroids to norovirus infection.

The molecular mechanisms behind infection and propagation of human restricted pathogens such as human norovirus (HuNoV) have defied interrogation because they were previously unculturable. However, human intestinal enteroids (HIEs) have emerged to offer unique models for targeted studies of intestinal biology, including inflammatory and infectious diseases. Carbohydrate-dependent histo-blood group antigens (HBGAs) are known to be critical for clinical infection.

Long-Lived Plasma Cells in Mice and Men.

Even though more than 30 years have passed since the eradication of smallpox, high titers of smallpox-specific antibodies are still detected in the blood of subjects vaccinated in childhood. In fact, smallpox-specific antibody levels are maintained in serum for more than 70 years. The generation of life-long immunity against infectious diseases such as smallpox and measles has been thoroughly documented.

Membrane Deformation Induces Clustering of Norovirus Bound to Glycosphingolipids in a Supported Cell-Membrane Mimic.

Quartz crystal microbalance with dissipation monitoring and total internal reflection fluorescence microscopy have been used to investigate binding of norovirus-like particles (noroVLPs) to a supported (phospho)lipid bilayer (SLB) containing a few percent of H or B type 1 glycosphingolipid (GSL) receptors. Although neither of these GSLs spontaneously form domains, noroVLPs were observed to form micron-sized clusters containing typically up to about 30 VLP copies, especially for B type 1, which is a higher-affinity receptor. This novel finding is explained by proposing a model implying that VLP-induced membrane deformation promotes VLP clustering, a hypothesis that was further supported by observing that functionalized gold nanoparticles were able to locally induce SLB deformation.