Organization of cellular receptors into a nanoscale junction during HIV-1 adhesion.
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.
Dobrowsky
Terrence M
TM
Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, Maryland, United States of America.
Daniels
Brian R
BR
Siliciano
Robert F
RF
Sun
Sean X
SX
Wirtz
Denis
D
D015704:CD4 Antigens / Q000032:analysis / Q000737:chemistry* / Q000378:metabolism; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D015699:HIV Envelope Protein gp120 / Q000737:chemistry* / Q000378:metabolism; D015497:HIV-1 / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D008390:Markov Chains; D008954:Models, Biological; D056004:Molecular Dynamics Simulation; D046912:Multiprotein Complexes / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D019713:Receptors, CCR5 / Q000032:analysis / Q000737:chemistry* / Q000378:metabolism; D013269:Stochastic Processes; D013816:Thermodynamics; D014771:Virion / Q000737:chemistry / Q000378:metabolism; D053585:Virus Attachment
D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; D046912:Multiprotein Complexes; D019713:Receptors, CCR5; C514793:gp120 protein, Human immunodeficiency virus 1