Covid: How Does It Replicate? (Transferred from Curious George)
By Shane Vogel '24
Everyone thought it was bad enough when SARS-CoV-2 started a global pandemic, infecting many with the dangerous disease known as Covid-19. In case you didn’t know, SARS-CoV-2 is the proper name for the physical virus itself. Covid-19, on the other hand, is the disease, or sickness, that infection from the virus causes. Meanwhile, coronavirus is just a category of virus that SARS-CoV-2 falls under, which one could call a “sequel” to SARS from the outbreak of 2003, as it is genetically related to the SARS virus. Back in late 2019, though, SARS-CoV-2 was only a small deal, with only a few cases reported. How did it become so widespread, then? Well, it’s all thanks to the virus’ replication.
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There are two main processes of viral replication, being the lytic cycle and the lysogenic cycle, which both involve infecting a host cell, as that is the basis for how all viruses replicate. SARS-CoV-2, though, doesn’t really follow the processes of either cycle beyond infecting a cell. In the lytic and lysogenic cycle, after infiltrating the cell, the viral genomes either attack chromosomes and kill the cell while reproducing through lysis (lytic) or leech off of them and reproduce while sparing the cell (lysogenic). Meanwhile, SARS-CoV-2 parasites off of both ribosomes and the ER to replicate. You see, SARS-CoV-2 is an RNA virus; that is, a virus that has its genetic information stored in the form of ribonucleic acid. It specifically falls under the RNA virus family of Nidovirales. RNA viruses, by that logic, have to copy their RNA in order to replicate. SARS-CoV-2 RNA genomes are unusually large compared to others, leading the virus to produce an increased amount of RNA-synthesizing and RNA-processing enzymes to handle it. So, as all viruses do, they sneak into the host cell and establish a presence in it. As mentioned before, viruses that follow the lytic or lysogenic cycle make their way into the nucleus, where the cell’s chromosomes are located. Since SARS-CoV-2 is different, though, it hangs out in the cytoplasm and dispenses its gRNA (genomic RNA) into the surrounding area. This is where the host cell’s ribosomes come in.
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Upon being released into the cytoplasm, the gRNA attracts the cells’ ribosomes, which processes the gRNA into a set of two “replicase” proteins, which are then split down into sixteen “non-structural” proteins, by enzymes integrated into viral proteins. These enzymes are known as proteases. Then, these non-structural proteins are formed together into RTC, standing for “replication-transcription complexe”. The RTC then envelopes itself in a double-membrane vesicle, which is created by the reformation of the ER (endoplasmic reticulum), marking the start of construction for a virus-producing organelle, or factory of sorts, all within the host cell. The RTC begins producing more gRNA through viral RNA synthesis. Instead of being used to create more RTCs, the new gRNA will be used to give DNA to newly replicated SARS-CoV-2 viruses.
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To create the actual “bodies” of the viruses, though, the RTC produces and enlists the help of mRNA (messenger RNA), which creates the genetic instructions for constructing physical parts of the virus. These instructions are sent to multiple locations, one of which is the ER, which the virus replication process continues to mess with. When it arrives, the mRNA instructs the ER (which usually is tasked with producing proteins for the host cell) to produce additional proteins necessary for the construction of the virus, such as the envelope, membrane, and spike proteins.
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As all of these components for virus replication are made, including the gRNA, they are sent to the ERGIC (endoplasmic reticulum-Golgi intermediate compartment), but it’s easier just to think of it as an enlarged vesicle produced and sent from the ER. The ERGIC is used as a “vessel” of sorts for the creation of a new virus. All of the components, as with a factory, are brought into a singular place and put together, leading to the formation of a newly replicated SARS-CoV-2 virus within the ERGIC. From there, the ERGIC travels to and releases the replicated virus from the cell membrane, allowing it to float around freely and infect others, giving them coronavirus and enabling it to undergo replication itself.
