Article

In Vitro Derived Dendritic Cells trans-Infect CD4 T Cells Primarily with Surface-Bound HIV-1 Virions

King's College London, United Kingdom
PLoS Pathogens (Impact Factor: 8.06). 02/2007; 3(1):e4. DOI: 10.1371/journal.ppat.0030004
Source: PubMed

ABSTRACT Author Summary
Dendritic cells (DCs) patrol peripheral mucosal sites, capturing and processing potential pathogens into antigenic peptides for presentation to T cells of lymphoid organs, and thereby initiating an immune response. HIV-1 had been proposed to use DCs as “Trojan horses,” hiding inside the DCs and surviving the degradation pathway to gain access to the lymph nodes and spread to the T cells. Our study challenges this “Trojan horse” model by showing that only HIV-1 virions bound to the surface of DCs, and not internalized virions, are transmitted to T cells. Even when T cells specifically recognized the antigen presented by DCs, the infection of T cells was principally mediated by virions remaining at the surface of the DCs. Interestingly, in this context of antigen-specific recognition, which increases the trafficking toward the immunological synapse of DC internal vesicles, where HIV-1 virions seem to hide, a few internal virions could infect T cells. Our findings suggest that in vivo transmission to T cells of HIV-1 virions captured by DCs should be more sensitive to neutralization than previously expected.

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Available from: Marielle Cavrois, Jul 20, 2015
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    • "To demonstrate that only virus binding is taking place at 4 °C, the cells were subjected to a pronase treatment (i.e. 200 μg/ml for 30 min at 4 °C) following incubation with HIV-1 as described previously (Cavrois et al., 2007). For virus internalization, the cells were washed once with ice-cold PBS, treated with 0.05% trypsin and 0.53 mM EDTA (Invitrogen) for 5 min at 37 °C (proteolysis was stopped by adding an equal volume of FBS), to remove all noninternalized viral particles, and washed twice with ice-cold PBS. "
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    • "Despite different approaches used in these studies, the dynamic trafficking and recycling of internalized HIV to DC surfaces could also mediate viral transmission, which should be an important consideration in DC-mediated HIV trans-infection. In addition, Cavrois et al. proposed that trypsin might be less potent than pronase at removing DC surface-bound HIV, but failed to present any results (Cavrois et al., 2007). By contrast, our comparison study indicated that pronase treatment (250 μg/ml) reduced iDC-and mDC-mediated HIV transmission by 48% and 24%, respectively (Wang et al., 2007b). "
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