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

 Pais-Correia1, A-M et al. Nat Med. 2010; 16: 83-9.

Speaker: Te-Hsin Yen (顏德欣)                                     Time: 15:10~16:00, May 5, 2010

Commentator: Dr. Yea-Lih Lin (林雅俐 老師)            Place: Room 601

Abstract:

Human T lymphotropic virus type I (HTLV-1) is a lymphotropic retrovirus that infects approximately 10-20 million people worldwide. It can cause adult T cell lymphatic leukaemia and inflammatory syndromes such as HTLV-1-associated myelopathy-tropical spastic paraparesis(HAM/TSP). Previous study has reported that HTLV-1-infected lymphocytes polarizes their microtubules and viral components upon contact with other T cells, forming virological synapses where HTLV-1 can spread from cell to cell¹. However, the localization of viral components and the subcellular compartments involved have remained poorly defined. Here, the authors carried out confocal and electron microscopy analyses for HTLV-1-infected cells. They found that HTLV-1-infected cells produced and transiently stored viral particles in extracellular viral assemblies. Extracellular matrix components provide attachment sites for viruses, including HTLV-1, facilitating their entry and concentration of budding viral particles into extracellular viral assemblies². The authors further observed the extracellular viral assemblies were rich in extracellular matrix component and cellular linker proteins, such as tetherin and galectin-3. Scanning electron microscopy revealed extracellular matrix components were transferred together with viral components from infected cells to target cells. Strikingly, the ability of HTLV-1-producing cells to infect target cells were strongly diminished after extracellular viral assemblies were removed. Taken together, this study reported that HTLV-1 virions are transiently kept in adhesive extracellular structures rich in carbohydrates and composed of virally induced extracellular matrix. Furthermore, these findings uncover a novel and major route for HTLV-1 transmission from cell to cell based on the biofilm-like extracellular viral assemblies.

References:

1.    Igakura, T. et al., 2003. Spread of HTLV-1 between lymphocytes by virus-induced polarization of the cytoskeleton. Science 299: 1713–1716.

2.      Jones, K.S. et al., 2005. Heparan sulfate proteoglycans mediate attachment and entry of human T-cell leukemia virus type 1 virions into CD4+ T cells. J. Virol. 79: 12692-702.