John T. Young

Retroviral Entry Mediated by Receptor Priming and Low pH Triggering of an Envelope Glycoprotein

Avian leukosis virus (ALV) has been used as a model system to understand the mechanism of pH-independent viral entry involving receptor-induced conformational changes in the viral envelope (Env) glycoprotein that lead to membrane fusion. Here, we report the unexpected finding that ALV entry depends on a critical low pH step that was overlooked when this virus was directly compared to the classical pH-dependent influenza A virus. In contrast to influenza A virus, receptor interaction plays an essential role in priming ALV Env for subsequent low pH triggering. Our results reveal a novel principle in viral entry, namely that receptor interaction can convert a pH-insensitive viral glycoprotein to a form that is responsive to low pH.

CAR1, a TNFR–Related Protein, Is a Cellular Receptor for Cytopathic Avian Leukosis–Sarcoma Viruses and Mediates Apoptosis

Viral envelope (Env)-receptor interactions have been implicated in the cell death associated with infection by subgroups B and D avian leukosis-sarcoma viruses (ALVs). A chicken protein, CAR1, was identified that permitted infection of mammalian cells by these viral subgroups. CAR1 bound to a viral Env fusion protein, comprising an ALV-B surface Env protein and the Fc region of an immunoglobulin, indicating that it is a specific viral receptor. CAR1 contains two extracellular cysteine-rich domains characteristic of the TNFR family and a cytoplasmic region strikingly similar to the death domain of TNFR1 and Fas, implicating this receptor in cell killing. Chicken embryo fibroblasts susceptible to ALV-B infection and transfected quail QT6 cells expressing CAR1 underwent apoptosis in response to the Env-Ig fusion protein, demonstrating that this cytopathic ALV receptor can mediate cell death.

The Man computer Interactive Data Access System: 25 Years of Interactive Processing

On 12 October 1998, it was the 25th anniversary of the Man computer Interactive Data Access System (McIDAS). On that date in 1973, McIDAS was first used operationally by scientists as a tool for data analysis. Over the last 25 years, McIDAS has undergone numerous architectural changes in an effort to keep pace with changing technology. In its early years, significant technological breakthroughs were required to achieve the functionality needed by atmospheric scientists. Today McIDAS is challenged by new Internet-based approaches to data access and data display. The history and impact of McIDAS, along with some of the lessons learned, are presented here.

Scaling Pattern to Variations in Size during Development of the Vertebrate Neural Tube

SUMMARY Anatomical proportions are robustly maintained in individuals that vary enormously in size, both within a species and between members of related taxa. However, the mechanisms underlying scaling are still poorly understood. We have examined this phenomenon in the context of the patterning of the ventral neural tube in response to a gradient of the morphogen Sonic hedgehog (SHH) in the chick and zebra finch, two species that differ in size during the time of neural tube patterning. We find that scaling is achieved, at least in part, by altering the sensitivity of the target cells to SHH and appears to be achieved by modulating the ratio of the repressive and activating transcriptional regulators, GLI2 and GLI3. This mechanism contrasts with previous experimental and theoretical analyses of morphogenic scaling that have focused on compensatory changes in the morphogen gradient itself.

Avian leukosis virus‐receptor interactions

Cellular receptors for subgroups A, B, D and E avian leukosis virus (ALV) have been identified and characterized. The Tva receptor for subgroup A ALV is a member of the low density lipoprotein receptor family of proteins. There is an accumulating body of evidence to suggest that this receptor binds specifically to subgroup A viral envelope (Env) proteins and induces conformational changes in Env proteins that are similar to those expected of the fusion active form of the viral glycoprotein. In contrast to the Tva receptor, Tvb receptors for viral subgroups B, D, and E are members of the tumour necrosis factor receptor (TNFR) protein family. Like several other members of this protein family, the Tvb proteins possess a cytoplasmic death domain and have been shown to induce cell death following binding to a soluble subgroup B Env‐specific reagent. These studies suggest a model in which the interactions between subgroup B and D Env proteins and their Tvb receptors contribute to the cytopathic effects that are...