Cell-Free versus Cell-to-Cell Infection by Human Immunodeficiency Virus Type 1 and Human T-Lymphotropic Virus Type 1: Exploring the Link among Viral Source, Viral Trafficking, and Viral Replication

Abstract

Human immunodeficiency virus type 1 (HIV-1) and human T-lymphotropic virus type 1 (HTLV-1) are complex retroviruses mainly infecting CD4؉ T lymphocytes. In addition, antigen-presenting cells such as dendritic cells (DCs) are targeted in vivo by both viruses, although to a lesser extent. Interaction of HIV-1 with DCs plays a key role in viral dissemination from the mucosa to CD4؉ T lymphocytes present in lymphoid organs. While similar mechanisms may occur for HTLV-1 as well, most HTLV-1 data were obtained from T-cell studies, and little is known regarding the trafficking of this virus in DCs. We first compared the efficiency of cell-free versus cell-associated viral sources of both retroviruses at infecting DCs. We showed that both HIV-1 and HTLV-1 cell-free particles are poorly efficient at productively infecting DCs, except when DC-SIGN has been engaged. Furthermore, while SAMHD-1 accounts for restriction of cell-free HIV-1 infection, it is not involved in HTLV-1 restriction. In addition, cell-free viruses lead mainly to a nonproductive DC infection, leading to trans-infection of T-cells, a process important for HIV-1 spread but not for that of HTLV-1. Finally, we show that T-DC cell-to-cell transfer implies viral trafficking in vesicles that may both increase productive infection of DCs ("cis-infection") and allow viral escape from immune surveillance. Altogether, these observations allowed us to draw a model of HTLV-1 and HIV-1 trafficking in DCs. Human T-lymphotropic virus type 1 (HTLV-1) and human immunodeficiency virus type 1 (HIV-1) infect 5 to 10 million (1) and 30 million (2) individuals worldwide, respectively. HTLV-1 is present in clusters of high endemicity such as in Japan, intertropical Africa, the Caribbean, and South America (3), whereas HIV-1 is pandemic. Interestingly, while both viruses infect CD4 ϩ T cells in vivo, the consequences of infection are opposite. After a long period of clinical latency, HTLV-1 infection leads either to adult T-cell leukemia (ATL) (4), an uncontrolled CD4 ϩ T lymphocyte proliferation with a very poor prognosis, or to an inflammatory disorder named HTLV-1-associated myelopathy/ tropical spastic paraparesis (HAM/TSP) in a fraction of infected individuals (5). On the other hand, HIV-1 is associated with CD4 ϩ T-lymphocyte death and causes AIDS (for a review, see reference 6).Interestingly, both viruses also infect antigen-presenting cells (APCs) to a lesser extent, among which are different subtypes of dendritic cells (DCs), such as myeloid DCs, monocyte-derived DCs (MDDCs), and plasmacytoid DCs (pDCs) (7-10). After viral entry in mucosal tissues during sexual intercourse or breastfeeding (11,12), DCs can be used as viral carriers, thus allowing the virus to reach lymphoid organs, where it infects CD4 ϩ T lymphocytes (13). Thus, both retroviruses may hijack (i) the ability of DCs to capture pathogens and (ii) their vesicular traffic pathways in order to be transmitted to target cells without requiring a productive viral cycle (i.e., by trans-infection of T cells). tra...

Tunneling Nanotubes as a Novel Route of Cell-to-Cell Spread of Herpesviruses

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Erythema Nodosum Caused by Mycobacterium tuberculosis in HTLV-1 Infected Patients

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