HIV and Mature Dendritic Cells: Trojan Exosomes Riding the Trojan Horse?

Nuria Izquierdo-Useros,Francesc E Borràs,Maria Carmen Puertas,Julià Blanco,Itziar Erkizia,Javier Martinez-Picado,Mar Naranjo-Gómez,Marianne Manchester

doi:10.1371/journal.ppat.1000740

Abstract

Exosomes are secreted cellular vesicles that can induce specific CD4+ T cell responses in vivo when they interact with competent antigen-presenting cells like mature dendritic cells (mDCs). The Trojan exosome hypothesis proposes that retroviruses can take advantage of the cell-encoded intercellular vesicle traffic and exosome exchange pathway, moving between cells in the absence of fusion events in search of adequate target cells. Here, we discuss recent data supporting this hypothesis, which further explains how DCs can capture and internalize retroviruses like HIV-1 in the absence of fusion events, leading to the productive infection of interacting CD4+ T cells and contributing to viral spread through a mechanism known as trans-infection. We suggest that HIV-1 can exploit an exosome antigen-dissemination pathway intrinsic to mDCs, allowing viral internalization and final trans-infection of CD4+ T cells. In contrast to previous reports that focus on the ability of immature DCs to capture HIV in the mucosa, this review emphasizes the outstanding role that mature DCs could have promoting trans-infection in the lymph node, underscoring a new potential viral dissemination pathway.

Highlights

Dendritic cells (DCs) scattered throughout the peripheral tissues act like sentinels and recognize a wide range of microorganisms
We have recently identified an human immunodeficiency virus (HIV) gp120independent mechanism of viral binding and endocytosis that is upregulated upon DC maturation [17], further supporting distinct works that have demonstrated that DC-SIGN is not responsible for HIV-1 binding to all DC subsets [21,44,45,46,47,48,49,50,51,52,53], and clearly highlighting that additional HIV-1 binding molecules remain to be identified
We suggest that HIV and other retroviruses could be exploiting this exosome antigen dissemination pathway intrinsic to mature DCs (mDCs), allowing the final transinfection of CD4+ T cells (Figure 3)

Summary

Introduction

Dendritic cells (DCs) scattered throughout the peripheral tissues act like sentinels and recognize a wide range of microorganisms. Separate pathways mediate the productive infection of DCs and their ability to capture and internalize HIV-1 in the absence of viral fusion [6].

Results

Conclusion