Selective transmission of R5 HIV-1 over X4 HIV-1 at the dendritic cell-T cell infectious synapse is determined by the T cell activation state.
Dendritic cells (DCs) are essential antigen-presenting cells for the induction of T cell immunity against HIV. On the other hand, due to the susceptibility of DCs to HIV infection, virus replication is strongly enhanced in DC-T cell interaction via an immunological synapse formed during the antigen presentation process. When HIV-1 is isolated from individuals newly infected with the mixture of R5 and X4 variants, R5 is predominant, irrespective of the route of infection. Because the early massive HIV-1 replication occurs in activated T cells and such T-cell activation is induced by antigen presentation, we postulated that the selective expansion of R5 may largely occur at the level of DC-T cell interaction. Thus, the immunological synapse serves as an infectious synapse through which the virus can be disseminated in vivo. We used fluorescent recombinant X4 and R5 HIV-1 consisting of a common HIV-1 genome structure with distinct envelopes, which allowed us to discriminate the HIV-1 transmitted from DCs infected with the two virus mixtures to antigen-specific CD4(+) T cells by flow cytometry. We clearly show that the selective expansion of R5 over X4 HIV-1 did occur, which was determined at an early entry step by the activation status of the CD4(+) T cells receiving virus from DCs, but not by virus entry efficiency or productivity in DCs. Our results imply a promising strategy for the efficient control of HIV infection.
Yamamoto
Takuya
T
Department of Immunology, National Institute of Infectious Diseases, Tokyo, Japan.
Tsunetsugu-Yokota
Yasuko
Y
Mitsuki
Yu-ya
YY
Mizukoshi
Fuminori
F
Tsuchiya
Takatsugu
T
Terahara
Kazutaka
K
Inagaki
Yoshio
Y
Yamamoto
Naoki
N
Kobayashi
Kazuo
K
Inoue
Jun-ichiro
J
D017951:Antigen Presentation; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology*; D002460:Cell Line; D003713:Dendritic Cells / Q000378:metabolism / Q000821:virology*; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D054992:Immunological Synapses / Q000276:immunology / Q000821:virology*; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008213:Lymphocyte Activation; D008856:Microscopy, Fluorescence; D019713:Receptors, CCR5 / Q000235:genetics / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism*
C527276:CXCR4 protein, human; D008164:Luminescent Proteins; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; C485184:enhanced green fluorescent protein; C413663:fluorescent protein 583; D049452:Green Fluorescent Proteins