In vivo expression profile of the antiviral restriction factor and tumor-targeting antigen CD317/BST-2/HM1.24/tetherin in humans

Abstract

Human CD317 is an intrinsic immunity factor that restricts the release of enveloped viruses, including the major pathogens HIV and Lassa virus, from infected cells in culture. Its importance for infection control in humans is unclear, due in part to its incompletely defined in vivo expression pattern. CD317 also has been proposed as a selective target for immunotherapy of multiple myeloma. To provide a framework for studies of the biological functions, regulation, and therapeutic potential of CD317, we performed microarray-based expression profiling in 468 tissue samples from 25 healthy organs from more than 210 patients. We found that CD317 protein was expressed to varying degrees in all organs tested and detected in a number of specialized cell types, including hepatocytes, pneumocytes, ducts of major salivary glands, pancreas and kidney, Paneth cells, epithelia, Leydig cells, plasma cells, bone marrow stromal cells, monocytes, and vascular endothelium. Although many of these cell types are in vivo targets for pathogenic viruses, restriction by CD317 or virus-encoded antagonists has been documented in only some of them. Limited cell type–dependent coexpression of CD317 with the IFN biomarker MxA in vivo and lack of responsive stimulation in organ explants suggest that interferons may only partially regulate CD317. This in vivo expression profiling sheds light on the biology and species-specificity of CD317, identifies multiple thus far unknown interaction sites of viruses with this restriction factor, and refutes the concept of its restricted constitutive expression and primary IFN inducibility. CD317's widespread expression calls into question its suitability as a target for immunotherapy.

Virus-Activated Interferon Regulatory Factor 7 Upregulates Expression of the Interferon-Regulated BST2 Gene Independently of Interferon Signaling

“…2). These data are consistent with recent reports that showed that monocytes displayed approximately 10 times more BST-2 molecules on a per-cell basis than T lymphocytes in healthy subjects (25,33), but they contrast with results of a recent study that did not detect basal BST-2 expression in leukocyte subsets (16). No significant upregulation was observed after treatment with inducers of NF-B (TNF-␣ and PMA) or NF-AT (ionomycin) pathways, even after different induction times (3 to 48 h) and increasing doses ( Fig.…”

Tetherin is a key effector of the antiretroviral activity of type I interferon in vitro and in vivo

“…As such, these viruses are likely to frequently encounter tetherin (28,29), and their replication is consequently inhibited. Indeed, this appears to be the situation for LP-BM5, whose replication and pathogenesis are attenuated by tetherin (Fig.…”

Equine Tetherin Blocks Retrovirus Release and Its Activity Is Antagonized by Equine Infectious Anemia Virus Envelope Protein

“…During viral infection, tetherins on the cell surface and viral envelope can prevent virion release either by direct cross-linking or by the formation of dimers between adjacent coiled-coil domains (20). Tetherin is constitutively expressed in mature B cells, some cancer cell lines, bone marrow stromal cells, monocyte-derived macrophages, and plasmacytoid dendritic cells, and its expression can be induced by type I and II interferon (IFN) treatment (21)(22)(23)(24)(25)(26)(27)(28). Thus, tetherin may play a fundamental role in the initiation and perpetuation of a virus-specific immune response.…”