CD317, also known as bone marrow stromal antigen 2 (BST-2) or tetherin, is a protein found on the surface of various cell types. This protein is a type II transmembrane glycoprotein that spans the cell membrane. CD317’s presence is particularly notable in mature B cells, plasma cells, and plasmacytoid dendritic cells, and its expression can be induced in many other cells in response to interferon signaling. It plays a role in the body’s defense mechanisms, particularly against pathogens.
CD317’s Primary Role in Immune Defense
CD317 functions as an antiviral restriction factor, playing a role in the innate immune system’s early defense against viral infections. Its primary mechanism involves physically “tethering” newly formed enveloped virus particles to the surface of infected cells. This tethering prevents the virions from fully detaching and spreading to other cells.
The unique structure of CD317 allows it to bridge the viral and cellular membranes, effectively trapping the virus particles. This action not only inhibits the release of individual virions but can also lead to the internalization and subsequent degradation of the tethered viral particles. This broad-spectrum antiviral activity has been observed against a variety of enveloped viruses, including Human Immunodeficiency Virus type 1 (HIV-1), as well as Lassa virus and Marburg virus.
Viral Strategies to Evade CD317
Viruses have evolved specific counter-measures to overcome the antiviral activity of CD317. For instance, HIV-1 produces an accessory protein called Vpu, which is specifically designed to antagonize CD317.
HIV-1 Vpu acts by reducing the amount of CD317 present on the cell surface, either by targeting it for degradation or by interfering with its trafficking. Vpu can trap CD317 molecules in intracellular compartments, preventing them from reaching the cell surface where they would otherwise tether budding viruses. This subversion of CD317’s normal cellular transport allows HIV-1 particles to be released efficiently from infected cells. While HIV-1 primarily uses Vpu, other viruses employ different strategies; for example, the Ebola virus glycoprotein (GP) has also been shown to counteract CD317, contributing to the virus’s ability to evade host defenses.
CD317 in Other Diseases
Beyond its role in viral infections, CD317 has implications in other health conditions, including cancer and inflammatory disorders. In cancer, CD317 is often overexpressed in various tumor types. This overexpression has been linked to promoting the survival, proliferation, and migration of cancer cells.
CD317 can protect tumor cells from apoptosis, or programmed cell death. Furthermore, CD317’s presence on tumor cells can offer protection against immunocytolysis, a process where immune cells destroy target cells. In inflammatory and autoimmune conditions, CD317 is involved in immune modulation. For example, specific subpopulations of mesenchymal stem/stromal cells (MSCs) that express CD317 have demonstrated enhanced anti-inflammatory activities.
Therapeutic Potential of CD317
Understanding CD317’s mechanisms and roles opens avenues for new therapeutic strategies. In the context of viral infections, therapies could aim to mimic or enhance CD317’s natural antiviral activity, potentially by developing drugs that prevent viral antagonists from counteracting CD317. This could lead to new antiviral treatments, particularly for viruses like HIV-1, where CD317’s tethering function is overcome by viral proteins.
For cancer, CD317 is being explored as a potential target for various therapies. Its overexpression on tumor cells makes it an attractive candidate for targeted immunotherapies. Research is investigating how modulating CD317 expression, perhaps by reducing it in tumor cells, could inhibit tumor growth or make cancer cells more susceptible to existing treatments and immune responses. For instance, an anti-CD317 antibody has been explored for treating multiple myeloma.