Abstract
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.
Highlights
HIV-1 infects T cells and monocyte lineage cells, including macrophages and dendritic cells (DCs), through CD4, the primary receptor for entry
Because DCs are one of the initial targets for HIV-1 infection and a source of virus dissemination, their role in AIDS pathogenesis has been the recent topic of much discussion [13,19,37]
The question that we sought to address was whether the predominance of R5 HIV-1 over X4 was determined at the level of DCs or CD4+ T cells and by what mechanism
Summary
HIV-1 infects T cells and monocyte lineage cells, including macrophages and dendritic cells (DCs), through CD4, the primary receptor for entry. The cellular tropism of HIV-1, i.e., macrophage (M)-tropic or T-cell line (T)-tropic, is determined by chemokine receptors Depending on whether they mainly use the CCR5 or CXCR4 entry coreceptors, primary isolates are defined as R5 for M-tropic and X4 for T-tropic variants, respectively [1]. R5 and X4 viruses are cytopathic [9], and R5 virus isolated from patients with late-stage disease are pathogenic to X4 in vitro [10]. These findings suggest that an yet-unknown selective mechanism that favors R5 virus exists during transmission and/or the early phases of infection in the host (review in [11])
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
