Organization of cellular receptors into a nanoscale junction during HIV-1 adhesion

• Published in: PLoS computational biology 2010-07, Vol.6 (7), p.e1000855-e1000855
• Main Authors: Dobrowsky, Terrence M, Daniels, Brian R, Siliciano, Robert F, Sun, Sean X, Wirtz, Denis
• Format: Article
• Language: English
• Subjects: Atoms & subatomic particles; Biophysics/Biomacromolecule-Ligand Interactions; Bond strength; Care and treatment; CD4 Antigens - analysis; CD4 Antigens - chemistry; CD4 Antigens - metabolism; Cell adhesion & migration; Cell Biology/Cell Adhesion; Cell Membrane - chemistry; Cell Membrane - metabolism; Computational Biology/Molecular Dynamics; Health aspects; HIV; HIV Envelope Protein gp120 - chemistry; HIV Envelope Protein gp120 - metabolism; HIV infection; HIV-1 - chemistry; HIV-1 - metabolism; HIV-1 - physiology; Human immunodeficiency virus; Human immunodeficiency virus 1; Infections; Infectious Diseases/HIV Infection and AIDS; Markov Chains; Mechanical properties; Microbiology; Models, Biological; Molecular Dynamics Simulation; Multiprotein Complexes - chemistry; Multiprotein Complexes - metabolism; Physiological aspects; Plasma; Protein Binding; Proteins; Receptors, CCR5 - analysis; Receptors, CCR5 - chemistry; Receptors, CCR5 - metabolism; Stochastic Processes; Thermal energy; Thermodynamics; Viral infections; Virion - chemistry; Virion - metabolism; Virus Attachment
• ISSN: 1553-7358; 1553-734X; 1553-7358
• DOI: 10.1371/journal.pcbi.1000855

The fusion of the human immunodeficiency virus type 1 (HIV-1) with its host cell is the target for new antiretroviral therapies. Viral particles interact with the flexible plasma membrane via viral surface protein gp120 which binds its primary cellular receptor CD4 and subsequently the coreceptor CCR5. However, whether and how these receptors become organized at the adhesive junction between cell and virion are unknown. Here, stochastic modeling predicts that, regarding binding to gp120, cellular receptors CD4 and CCR5 form an organized, ring-like, nanoscale structure beneath the virion, which locally deforms the plasma membrane. This organized adhesive junction between cell and virion, which we name the viral junction, is reminiscent of the well-characterized immunological synapse, albeit at much smaller length scales. The formation of an organized viral junction under multiple physiopathologically relevant conditions may represent a novel intermediate step in productive infection.