The Virological Synapse

Synapse As obligate intracellular parasites, viruses have evolved diverse mechanisms to enter and exit from host cells. A requirement that is shared by all animal viruses is the use of cellular receptors for entry into cells to initiate viral infection. Receptors can function in virus attachment to the cell surface and can also mediate virus internalization and penetration of the cell membrane. Receptors are often grouped into “primary receptors” and “secondary receptors” or “co-receptors” depending either on their function in the virus entry process or historical precedence.

Viruses can be classified into two broad groups: enveloped and non-enveloped. Direct cell-to-cell spread has only been described for enveloped viruses. Viruses that spread directly from infected to uninfected cells can avoid the obstacles to infection which occur for for infection via free virus particles (biophysical and immunological). Once the initial infection has occurred, the cell-to-cell mode of virus spread enables direct infection of target cells by adjacent infected cells – a very efficient process.

Direct cell-to-cell spread requires intimate contact between cells and can occur at tight junctions between cells or neurological synapses. Immune cells contain machinery that allows them to polarize their secretory apparatus towards a second cell that is involved in an immunological synapse. This machinery can be subverted by retroviruses such as HTLV-1 and HIV-1 to form a virological synapse. Virions bud from the infected cell into the synapse, from where they fuse with the target-cell plasma membrane. Certain viruses have therefore engineered novel structures in infected cells to promote more efficient spread within the host.

Avoiding the void: cell-to-cell spread of human viruses. 2008 Nature Reviews Microbiology 6: 815-826. doi:10.1038/nrmicro1972
The initial stages of animal virus infection are generally described as the binding of free virions to permissive target cells followed by entry and replication. Although this route of infection is undoubtedly important, many viruses that are pathogenic for humans, including HIV-1, herpes simplex virus and measles, can also move between cells without diffusing through the extracellular environment. Cell-to-cell spread not only facilitates rapid viral dissemination, but may also promote immune evasion and influence disease. This review discusses the various mechanisms by which viruses move directly between cells and the implications of this for viral dissemination and pathogenesis.

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