There are five key steps in viral replication, which vary slightly depending on the structure of the virus. These steps are attachment, entry into a cell, uncoating, replication and shedding.
Attachment and Entry
Most viruses use ligand-receptor interactions to bind to cells. The ligand is usually an attachment protein on the capsid or envelope of the virus. Depending on the nature of the virus, these attachment proteins may bind to a specific receptor to target a specific tissue, or may bind to numerous receptors to infect many types of cells.
After binding to a cell, the virus can either enter via endocytosis or fusion. Nonenveloped viruses must enter the cell via endocytosis. Endocytosis involves the cell ingesting the ligand-bound receptor, enclosing the virus in a clathrin-coated pit. The virus can then disrupt the endosomal membrane to escape into the cytoplasm. Enveloped viruses are able to enter cells via fusion, where the viral envelope fuses with the cell membrane. This allows the now unenveloped nucleocapsid to enter the cell cytoplasm.
Uncoating
Uncoating is the process where the capsid is removed, to reveal the viral genome. Many viruses will uncoat themselves as part of the entry process. Some viruses use the binding of their ligand to a cell receptor to trigger a structural change that releases the viral genome. Others may use host proteases from endosome fusion to lysosomes to remove their capsid proteins. The end results for all of these processes is the viral genome floating freely in the cytoplasm, ready for replication.
Replication
Replication of viruses requires two things: conversion of viral mRNA into viral proteins, and replication of the viral genome. Depending on the type of virus, these processes can be carried out in different ways. These methods are summarized below:
| Type of Virus | Viral Genome Replication Method | Protein Synthesis Method |
|---|---|---|
| +ssRNA viruses (e.g. picornavirus, flavivirus) | Virus encodes production of RNA-dependent RNA polymerase -> synthesizes complementary negative-sense RNA template -> template used to produce more positive RNA strands | Viral genome functions directly as mRNA -> translated by ribosomes to produce proteins |
| -ssRNA viruses (e.g. influenza) | Virus contains RNA-dependent RNA polymerase -> produces a positive strand template -> template used to produce more negative RNA strands | Virus contains RNA-dependent RNA polymerase -> enzyme produces a positive strand template used for protein production |
| dsRNA viruses (e.g. rotavirus) | Virus encodes RNA-dependent RNA polymerase -> produces positive strand template used for synthesizing dsRNA | Virus encodes RNA-dependent RNA polymerase -> transcribes positive strand template for protein production |
| Retroviruses (e.g. FIV) | Virus contains RNA-dependent DNA polymerase -> uses virus’ +ssRNA to produce DNA strand -> integrates into host DNA -> replicated by host DNA-dependent RNA polymerases | Virus contains RNA-dependent DNA polymerase -> uses virus’ +ssRNA to produce DNA strand -> integrates into host DNA -> transcription of viral proteins during normal cell protein production |
| ssDNA viruses (e.g. parvovirus) | Uses host DNA polymerase to replicate genome | Uses host RNA polymerase to produce positive strand mRNA template used for protein production |
| dsDNA viruses (e.g. papillomavirus) | Uses host or virus-encoded DNA polymerase to replicate genome | Uses host RNA polymerase to produce positive strand mRNA template used for protein production |
Shedding
Once the viral genome and proteins are formed, new virions are assembled. The virus is now ready to leave the cell to infect other cells or hosts.
Enveloped viruses are released by budding, which allows them to wrap themselves in host membrane to produce their characteristic envelope. These viruses typically do this by activating apoptosis, which programs the cell to begin blebbing its cell membrane.
Nonenveloped viruses are usually released when the cell undergoes necrosis, with lysis of the cell membrane. To trigger cell death, viruses may restrict cell metabolism, alter the cell cytoskeleton, affect membrane structure or trigger the release of lysosomal enzymes. Some viruses produce viroporins, which form pores in cell membranes.
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