Lorraine M. Albritton

B cells and reduced disease in naive autoimmune mice, indicating that disease control was cell-mediated. Sustained B cell depletion with CD19-targeted CAR T cell immunotherapy is a stable and effective strategy to treat murine lupus, and its effectiveness should be explored in clinical trials for lupus.

The liver regulates the supply of amino acids required for protein synthesis and intermediary metabolism between feeding and fasting in mammals. The flux of amino acids between the liver and other tissues is determined, in part, by the activity of specific carrier proteins. We have identified a carrier of the cationic amino acids arginine, lysine, and ornithine in mouse liver that is closely related to a previously identified transporter with the same substrate specificity expressed in nonhepatic tissues. Uptake studies were performed in Xenopus oocytes injected with cRNA encoding these proteins. The comparison of the two transporters in these studies demonstrated that, unlike the widely-expressed transporter, arginine uptake mediated by the liver carrier is significant only at substrate concentrations that exceed systemic plasma levels and is less dependent on the intracellular concentration of cationic amino acids. These properties enable hepatocytes expressing this carrier to remove excess cationic amino acids from the blood without interfering with their uptake by nonhepatic tissues that express the related transporter.

Infection of rodent cells by ecotropic type C retroviruses requires the expression of a cationic amino acid transporter composed of multiple membrane-spanning domains. By exchanging portions of cDNAs encoding the permissive mouse and nonpermissive human transporters and examining their abilities to specify virus infection upon expression in human 293 cells, we have identified the amino acid residues in the extracellular loop connecting the fifth and sixth membrane-spanning segments of the mouse transporter that are required for both envelope gp70 binding and infection. These findings strongly suggest that the role of the mouse transporter in determining infection is to provide an envelope-binding site. This role is analogous to those of host membrane proteins composed of a single membrane-spanning domain that serve as binding proteins or receptors for other enveloped viruses such as human immunodeficiency virus, Epstein-Barr virus, and murine and human coronaviruses.