Abstract
HIV-1 cell-to-cell transmission is key for an effective viral replication that evades immunity. This highly infectious mechanism is orchestrated by different cellular targets that utilize a wide variety of processes to efficiently transfer HIV-1 particles. Dendritic cells (DCs) are the most potent antigen presenting cells that initiate antiviral immune responses, but are also the cells with highest capacity to transfer HIV-1. This mechanism, known as trans-infection, relies on the capacity of DCs to capture HIV-1 particles via lectin receptors such as the sialic acid-binding I-type lectin Siglec-1/CD169. The discovery of the molecular interaction of Siglec-1 with sialylated lipids exposed on HIV-1 membranes has enlightened how this receptor can bind to several enveloped viruses. The outcome of these interactions can either mount effective immune responses, boost the productive infection of DCs and favour innate sensing, or fuel viral transmission via trans-infection. Here we review these scenarios focusing on HIV-1 and other enveloped viruses such as Ebola virus or SARS-CoV-2.
Highlights
The relevance of this mechanism prompted extensive research in human immunodeficiency virus type 1 (HIV-1) transmission allowing for the identification of several types of synapses involving: susceptible cells to infection, such as CD4+ T cells or macrophages [4,9]; non-susceptible cells to infection, such as endothelial cells or dendritic cells (DCs) [10,11]; and different mechanisms of membrane dynamics [12]
In this review we focus on how DCs, which are the most potent antigen presenting cells (APCs) found in our organism [34,35], are the ones with greater capacity to boost HIV-1 transmission via a cell-to-cell transfer mechanism co-opted by other enveloped viruses
Several studies suggested that other receptors aside from DC-specific intercellular adhesion molecule-3grabbing non-integrin (DC-SIGN) operated in HIV-1 transmission [79,80,81,82,83,84,85,86]. This was suspected because DC maturation greatly increased HIV-1 trans-infection capacity while it decreased the expression of DC-SIGN [86], and because antibodies directed against DC-SIGN were not able to consistently block HIV-1 transmission [82]. Such inconsistencies led to the identification, almost a decade ago, of the sialic acid-binding immunoglobulin-like lectin 1 (Siglec-1/CD169) as the key molecule for DC-mediated HIV-1 trans-infection [87,88]
Summary
Cellular Mechanisms of HIV-1 Spread Several viruses have the ability to hijack pre-existing mechanisms of cellular communication to facilitate direct cell-to-cell viral spread [1,2,3], and the human immunodeficiency virus type 1 (HIV-1) is not an exception [1,4]. The first detailed description of a stable cellular junction between infected and non-infected cells to facilitate viral spread, known as virological synapse (VS), was reported for the human T cell leukaemia virus type 1 (HTLV-1), which is inefficient at infecting T cells and requires cellular contacts for effective spread [6] Soon after this description, several studies showed co-clustering of HIV-1 proteins with their receptors CD4 and CXCR4, together with a massive viral transmission at the stable interface formed between HIV-1-infected and non-infected CD4+ T cells [7,8], expanding the concept of vs to HIV-1. In this review we focus on how DCs, which are the most potent APCs found in our organism [34,35], are the ones with greater capacity to boost HIV-1 transmission via a cell-to-cell transfer mechanism co-opted by other enveloped viruses
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