Simultaneous cell-to-cell transmission of human immunodeficiency virus to multiple targets through polysynapses.
Human immunodeficiency virus type 1 (HIV-1) efficiently propagates through cell-to-cell contacts, which include virological synapses (VS), filopodia, and nanotubes. Here, we quantified and characterized further these diverse modes of contact in lymphocytes. We report that viral transmission mainly occurs across VS and through "polysynapses," a rosette-like structure formed between one infected cell and multiple adjacent recipients. Polysynapses are characterized by simultaneous HIV clustering and transfer at multiple membrane regions. HIV Gag proteins often adopt a ring-like supramolecular organization at sites of intercellular contacts and colocalize with CD63 tetraspanin and raft components GM1, Thy-1, and CD59. In donor cells engaged in polysynapses, there is no preferential accumulation of Gag proteins at contact sites facing the microtubule organizing center. The LFA-1 adhesion molecule, known to facilitate viral replication, enhances formation of polysynapses. Altogether, our results reveal an underestimated mode of viral transfer through polysynapses. In HIV-infected individuals, these structures, by promoting concomitant infection of multiple targets in the vicinity of infected cells, may facilitate exponential viral growth and escape from immune responses.
Department of Virology, Virus and Immunity Unit, Institut Pasteur, URA CNRS 3015, Paris Cedex 15, France.
Dominika
D
Rudnicka
Jérôme
J
Feldmann
Françoise
F
Porrot
Steve
S
Wietgrefe
Stéphanie
S
Guadagnini
Marie-Christine
MC
Prévost
Jérôme
J
Estaquier
Ashley T
AT
Haase
Nathalie
N
Sol-Foulon
Olivier
O
Schwartz
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000648:ultrastructure / Q000821:virology*; D005260:Female; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D019169:Jurkat Cells; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism*; D008251:Macaca; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D011554:Pseudopodia / Q000821:virology; D014779:Virus Replication; D054299:env Gene Products, Human Immunodeficiency Virus / Q000378:metabolism; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000378:metabolism*
D016169:Lymphocyte Function-Associated Antigen-1; D054299:env Gene Products, Human Immunodeficiency Virus; D054301:gag Gene Products, Human Immunodeficiency Virus