Human immunodeficiency virus type 1 virological synapse formation in T cells requires lipid raft integrity.
Human immunodeficiency virus type 1 (HIV-1) can spread directly between T cells by forming a supramolecular structure termed a virological synapse (VS). HIV-1 envelope glycoproteins (Env) are required for VS assembly, but their mode of recruitment is unclear. We investigated the distribution of GM1-rich lipid rafts in HIV-1-infected (effector) T cells and observed Env colocalization with polarized raft markers GM1 and CD59 but not with the transferrin receptor that is excluded from lipid rafts. In conjugates of effector T cells and target CD4+ T cells, GM1, Env, and Gag relocated to the cell-cell interface. The depletion of cholesterol in the infected cell dispersed Env and GM1 within the plasma membrane, eliminated Gag clustering at the site of cell-cell contact, and abolished assembly of the VS. Raft integrity is therefore critical for Env and Gag co-clustering and VS assembly in T-cell conjugates.
Jolly
Clare
C
The Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, United Kingdom.
Sattentau
Quentin J
QJ
D000956:Antigens, Viral / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000821:virology; D005677:G(M1) Ganglioside / Q000378:metabolism; D015497:HIV-1 / Q000472:pathogenicity* / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D019169:Jurkat Cells; D021962:Membrane Microdomains / Q000378:metabolism / Q000821:virology*; D016253:Microscopy, Immunoelectron; D013601:T-Lymphocytes / Q000378:metabolism / Q000821:virology*
D000956:Antigens, Viral; C070924:Env-5 glycoprotein, HTLV-I; D005677:G(M1) Ganglioside