Unveiling Hidden Pathways: The Evolution and Mechanics of Viral Cell-to-Cell Transmission
Posted on January 18, 2024 • 3 minutes • 459 words • Other languages: Русский
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Viruses depend on host organisms for replication, as they are parasites that exist inside cells. Over time, they have evolved to hijack host cellular mechanisms to suit their reproductive needs, showing similarities in the phases of their life cycle such as entry, penetration, assembly, and release. The past three decades have seen extensive research on many of these stages. Yet, only recently have we started to uncover new aspects of viral life cycles. A particularly intriguing new discovery is the method of cell-to-cell transmission, which is gaining attention for its role in viral spread and its potential implications in treating persistent viral infections like AIDS and hepatitis.
Previously, it was assumed that viruses spread to adjacent cells solely through release into the extracellular space from an infected cell. Contrary to this belief, a new mode of infection has been identified, where a virus can infect a neighboring cell without being released externally. This process, known as cell-to-cell transmission or spread, has four identified mechanisms. Firstly, in viruses like retroviruses and herpesviruses, cell-to-cell transmission happens through the fusion of plasma membranes, allowing viral capsids to move directly between infected and uninfected cells without needing an envelope. Secondly, some viruses, including herpesviruses and HCV, spread via tight junctions where the virus moves basolaterally from an infected cell and gets trapped between cell membranes at the tight junctions, then enters the target cell using its viral entry receptors. The third method involves neural synapses, seen in viruses like Rhabdovirus, herpesviruses, and paramyxoviruses, where virions, either complete or as naked cores, gather in the synaptic cell and then bud into the synaptic space or are released into it from synaptic vesicles, eventually fusing with or being endocytosed by the opposite synaptic cell. The fourth mechanism is through virological synapses, similar to immunological synapses in immune cells. Here, an infected cell directs viral budding towards a receptor-bearing target cell, creating a structure called a “virological synapse,” where virions bud into the cleft and then fuse with the target cell. HIV and HTLV-1 are examples of viruses that use this transmission mode.
| Four modes of cell-to-cell spread. (A) Via plasma membrane fusion. (B) Across tight junction. (C) Across a neural synapse. (D) Across a virological synapse. |
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Why is cell-to-cell transmission advantageous? It allows viruses to spread directly to adjacent uninfected cells through contact, bypassing diffusion. More crucially, viruses in this transmission mode are shielded from neutralizing antibodies. This was discovered in experiments exploring viral transmission that is resistant to neutralizing antibodies. Interestingly, cell-to-cell transmission has only been observed in enveloped viruses, not in non-enveloped viruses. This might be because non-enveloped viruses, which release a large number of virions suddenly during cell lysis, don’t benefit from cell-to-cell transmission.
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