Biofilm-like extracellular viral assemblies mediate HTLV-1 cell-to-cell transmission at virological synapses

The virus HTLV-1 is thought to pass between cells through synapses formed when infected lymphocytes make contact with other T cells. Isabelle Thoulouze and her colleagues uncover an alternative mechanism for the cell-to-cell transmission of this virus. They show that HTLV-1 virions bud at the plasma membrane and are held at the cell surface in structures reminiscent of bacterial biofilms. When infected lymphocytes make contacts with other cells, the adhesive viral assemblies are rapidly transferred to to the surface of the new lymphocyte, from which the virions mediate a new round of infection. Human T cell leukemia virus type 1 (HTLV-1) is a lymphotropic retrovirus whose cell-to-cell transmission requires cell contacts. HTLV-1–infected T lymphocytes form 'virological synapses', but the mechanism of HTLV-1 transmission remains poorly understood. We show here that HTLV-1–infected T lymphocytes transiently store viral particles as carbohydrate-rich extracellular assemblies that are held together and attached to the cell surface by virally-induced extracellular matrix components, including collagen and agrin, and cellular linker proteins, such as tetherin and galectin-3. Extracellular viral assemblies rapidly adhere to other cells upon cell contact, allowing virus spread and infection of target cells. Their removal strongly reduces the ability of HTLV-1–producing cells to infect target cells. Our findings unveil a novel virus transmission mechanism based on the generation of extracellular viral particle assemblies whose structure, composition and function resemble those of bacterial biofilms. HTLV-1 biofilm-like structures represent a major route for virus transmission from cell to cell.