Masters of manipulation: Viral modulation of the immunological synapse

Abstract

In order to thrive, viruses have evolved to manipulate host cell machinery for their own benefit. One major obstacle faced by pathogens is the immunological synapse. To enable efficient replication and latency in immune cells, viruses have developed a range of strategies to manipulate cellular processes involved in immunological synapse formation to evade immune detection and control T-cell activation. In vitro, viruses such as human immunodeficiency virus 1 and human T-lymphotropic virus type 1 utilise structures known as virological synapses to aid transmission of viral particles from cell to cell in a process termed trans-infection. The formation of the virological synapse provides a gateway for virus to be transferred between cells avoiding the extracellular space, preventing antibody neutralisation or recognition by complement. This review looks at how viruses are able to subvert intracellular signalling to modulate immune function to their advantage and explores the role synapse formation has in viral persistence and cell-to-cell transmission.

The Immunological Synapse: An Emerging Target for Immune Evasion by Bacterial Pathogens

“…As the platform where the T cell response to antigen recognition is coordinated, the IS represents one of such vulnerabilities. This is witnessed by evidence accumulated over the past several years showing that the processes that regulate IS assembly, from TCR signaling, to cytoskeleton dynamics, to vesicular trafficking, are targeted by lymphotropic viruses to thwart the antiviral T cell response and infect neighboring cells while remaining undetectable ( 86 , 87 ). Interesting, IS targeting is exploited also by tumor cells to suppress antitumor immunity through both contact-dependent and -independent mechanisms, as amply documented in chronic lymphocytic leukemia ( 103 ).…”

“…Since the seminal discovery that lymphotropic viruses such as HIV-1 and HTLV-1 not only exploit the IS to evade the T cell response but apply the same building principles to form the virological synapse, a platform for cell-to-cell transmission, the IS has attracted major interest as a target for immune evasion by viral pathogens ( 86 , 87 ). Whether and how bacterial pathogens can subvert IS assembly to avoid T cell immunity not indirectly by modulating DC activation and function, but directly, are questions that are only beginning to be formulated.…”

From the Catastrophic Objective Irreproducibility of Cancer Research and Unavoidable Failures of Molecular Targeted Therapies to the Sparkling Hope of Supramolecular Targeted Strategies

“…A viral (virological) synapse is a cellular junction that has the characteristic features of a synapse. Viruses such as the herpes simplex virus (HSV), human immunodeficiency virus (HIV), and human T-lymphotropic virus (HTLV) form these junctions between the infected ("donor") and uninfected ("target") cells and, in such a way, achieve direct cell-cell viral transmission; thus, they escape destruction by the immune system [130][131][132].…”

G2-S16 Polyanionic Carbosilane Dendrimer Can Reduce HIV-1 Reservoir Formation by Inhibiting Macrophage Cell to Cell Transmission

“…Infected macrophages are one of the main factors in HIV-1 spreading to different tissues and organs [27]. This is due to macrophages' ability to carry the virus without losing infectivity for long times, leading to a higher infectivity when they contact with CD4/CD8 T lymphocytes due to the cellular synapses [28,29]. As commented before, these synapses protect viruses from antiviral molecules and immune defenses present in the extracellular medium and are not capable of internalizing into the cell [15].…”