Virus uncoating is the process where a virus sheds or removes or alters its protective protein coat (capsid) to release its genetic material inside a host cell, initiating the infection. This crucial step allows the viral genome to take control of the host cell’s machinery for replication and production of new viruses. How the viruses remove the capsid depends on how the virus enters the host cell.

Mechanisms of virus uncoating

  1. Virus uncoating at the plasma Membrane: Certain viruses, like enveloped viruses, can directly fuse their viral envelope with the host cell membrane. Fusion is often triggered by changes in the viral envelope proteins induced by factors such as low pH in endosomes or direct contact with the host cell membrane. Changes in pH or other environmental factors can trigger conformational changes in viral proteins, exposing regions that promote fusion and uncoating. Once fusion occurs, the viral genome, which is typically composed of either RNA or DNA, is released into the cytoplasm. This marks the completion of the uncoating process for these viruses

2. Virus uncoating during the Receptor-mediated endocytosis:

Many non-enveloped viruses enter host cells through receptor-mediated endocytosis. The virus binds to specific receptors on the cell surface, triggering the uptake of the virus-receptor complex into the cell within endocytic vesicles. The interaction between the viral capsid and cellular receptors can trigger conformational changes in the capsid structure, priming it for subsequent uncoating steps.

    • The acidic environment within the endosomes can induce conformational changes in the viral capsid, leading to the exposure of regions that facilitate uncoating.
    • Enzymes within the endosomes may also contribute to the degradation or alteration of the viral capsid, allowing the release of the viral genome into the cytoplasm.

3. Virus uncoating during entry by direct penetration:

    • Some non-enveloped viruses can enter cells by direct penetration through the cell membrane. This may involve the formation of pores or channels in the host cell membrane, allowing the viral genome to be delivered directly into the cytoplasm.
    • The disruption of the viral capsid structure during this process exposes the genetic material for subsequent steps in the viral life cycle.

4. Virus uncoating by host cell and viral proteases:

  • Cellular proteases can contribute to capsid priming by cleaving viral proteins. The activity of host cell proteases may be necessary for initiating the uncoating process by disrupting the integrity of the viral capsid.
  • Some viruses encode proteases within their capsid or as part of their polyprotein that play a role in capsid priming. These proteases may cleave specific capsid proteins, leading to structural changes and exposing regions required for uncoating.

5. Virus uncoating by mechanical forces and temperature

    • Physical forces, such as mechanical stress or shear forces, can contribute to the disruption of the viral capsid. For example, during viral entry, the virus may experience mechanical forces that lead to structural changes, exposing the genetic material.
    • Temperature variations can influence the stability and conformation of viral capsids. Changes in temperature, either during viral entry or within specific cellular compartments, may prime the capsid for uncoating.

6. Virus uncoating controlled by host factors: Host cell factors, such as chaperone proteins or other cellular components, may interact with the viral capsid and induce conformational changes. These changes can make the capsid more susceptible to subsequent uncoating steps.

7. Pressure within the capsid: Pressure within the virus particle built up by electrostatic repulsion weakens the pentons
pressure between the negatively charged dsDNA strands, DNA bending and entropic components facilitate softening of capsid leading to uncoating