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

PLoS Pathogens

Jun-ichiro Inoue¹  Yoshio Inagaki²  Yu-ya Mitsuki²  Kazutaka Terahara²  Fuminori Mizukoshi²  Takuya Yamamoto²  Naoki Yamamoto²  Takatsugu Tsuchiya³  Kazuo Kobayashi³  Yasuko Tsunetsugu-Yokota⁴ 

[1] AIDS Research Center, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo, Japan;Department of Immunology, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo, Japan;Department of Molecular Virology, Bio-Response, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan;Division of Cellular and Molecular Biology, Department of Cancer Biology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo, Japan

关键词: T cells;    HIV-1;    Viral replication;    Synapses;    Coreceptors;    Viral entry;    Antigen-presenting cells;    HIV;   

DOI  :  10.1371/journal.ppat.1000279

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY