Question

Describe the viral uncoating process in greater detail USING AT LEAST THREE (3) SPECIFIC virus examples in your answer.

Answer 1

All viruses whether enveloped and non-enveloped – protect their genome inside a protein shell referred to as a capsid. Most capsids are assembled from regular capsomere units, forming helical or icosahedral structures built from a limited number of capsid proteins. All virus capsids possess a built-in capacity for disassembly, referred to as structural metastability: assembled as stable structures during morphogenesis inside producer cells, capsids must be efficiently disassembled or disintegrated in newly infected cells. For some viruses, the environment in which assembly/egress and uncoating occur are homologous.

Below are the uncoating mechanisms of three viuses

• ADENOVIRUS- These viruses go through a step-wise uncoating program that begins during virus assembly and proceeds through distinct disassembly intermediates during the entry process. The first capsid-priming step occurs during virion morphogenesis. It is mediated by the virus-encoded protease that facilitates the transition from immature to mature virions through proteolytic cleavage .Adenovirus uncoating relies on multiple priming steps during morphogenesis, in the extracellular space, upon binding of their receptors, within endosomes, inside the cytosol, and at the nuclear pore.

• POLYOMAVIRUSES- Crystallographic data suggests that PYs do not change their structure upon contact with receptors. This suggests that these viruses, unlike adenoviruses, are not primed for uncoating at the cell surface. Upon endocytosis, PYs are routed to the endoplasmic reticulum (ER) in a receptor-dependent fashion . During this journey, PYs encounter low pH, proteases, and additional endosomal cues involved in the uncoating of other viruses. However PYs do not undergo proteolytic cleavage and with the exception of BK virus, remain structurally unchanged until reaching the ER. As the mechanisms of nuclear translocation and the configuration/composition of the subviral structure inside the nucleus is not known, further research will be required to clarify the last step of polyomavirus uncoating.

• POXVIRUSES- poxvirus genome-release and replication occur in the cytoplasm, these viruses face particular challenges related to innate DNA-sensing and antiviralresponse. As a consequence, they have evolved a highly regulated, multi-step core-disassembly program. Elegant biochemical studies in the 1960s demonstrated that poxvirus uncoating is a two-step process. The first stage commences immediately after membrane fusion and is referred to as “core activation”, the second stage, cytoplasmic genome release, occurs after a lag-period due to the requirement for expression of a virus-encoded uncoating protein.