It’s day one post Pfizer’s COVID-19 Vaccine and my arm is minimally sore, I have no headache, no fatigue, I’ve been home today and chasing multiple children without any noticeable symptoms. Since my writing style doesn’t lend itself well to sass and snark, I’d like to take this update to talk about viruses and mRNA vaccines and how they’re similar and related. So here goes….
Viruses and mRNA vaccines
OK. So lets talk about viruses, DNA/RNA, and the new mRNA vaccines. I am going to try and keep this at a 6th grade level (or lower, if I can), so that it can be widely read and easily understood. While keeping our reading level in the 5th/6th grade range, we will be painting with a broad brush, and will be covering some in-depth topics at a high level, so it’s highly likely that we will not cover all of the atypical situations that occur in nature. I will try and point out these exceptions as I can, but I will undoubtably miss some while we cover these topics.
So let’s start with general information about viruses. When we talk about Viruses, we separate them into two broad categories and four Realms. The primary categories that we divide viruses into are based on the genetic structures contained within the virus: either DNA or RNA. The four Realms delve into the different ways DNA and RNA can be contained in the nucleocapsid (protein structure that holds the genetic material). Three of the Realms cover DNA viruses and one Realm covers all of the RNA viruses. The names of these Realms tell us a lot about the type of virus and whether the virus is a RNA virus (Riboviria, due to the base sugar seen in RNA – ribose), a double stranded DNA virus (Duplodnaviria, from duplo- – two, -dna – DNA, -viria – virus), a single-stranded DNA virus (Monodnaviria, from mono- – one, -dna – DNA, -viria – virus), or a non-tailed/tailless DNA viruses (Varidnaviria, likely from vari- – variant, -dna – DNA, -viria – Virus).
Where this is important is how viruses attach and utilize cells to enter cells, replicate, and then release the newly manufactured viruses.
There are two primary mechanisms for viruses to enter the cell. They can attach to the cellular wall by means of target proteins and enzymes which cause both the cell wall proteins and the viral proteins to clave (break apart) and then fuse together. We see this in the way SARS-CoV-2 targets ACE2 receptors and bind to these receptors, allowing the virus to inject its RNA into the cell for reproduction of new viruses. Other viruses are completely absorbed into the cell, where the contents and viral capsid remain intact in the targeted cell.
As a general rule, RNA viruses are incapable of altering a cells DNA (an important exception would be the HIV virus and other retroviruses). Retroviruses are viruses which are able to create reverse transcriptase, an enzyme which allows the RNA virus to work backwards and create DNA from RNA, along with structures/enzymes which insert the viral genetic material into the cells DNA. This process ensures that the viruses genetic material/instructions are kept safe for later. This process is different from most latent (sleeping) viruses. Most latent viruses are contained in capsules outside of the nucleus (a good example of this are viruses which are in the family Herpesviridae, which includes viruses such as the varicella zoster virus (VZV) which cause chickenpox and shingles and the herpes viruses (HSV 1 and 2) which cause cold sores and genital herpes. Neither HSV 1/2 nor VZV alter the genetic material of the cell, they encapsulate their genetic material within the cell, but outside the nucleus, for later use. This latent state of Herpesviridae viruses allow them to reactivate many years later, causing shingles (zoster stage of Varicella), meningitis (both HSV and VZV), pancreatitis, hepatitis, etcetera.
Unlike DNA viruses which can see latent phases of infection, latent infection with RNA viruses is extremely rare. HIV is probably the most studied example of an exception to this rule. The ability to produce a reverse transcriptase (the enzyme needed to take RNA to DNA) is produced by very few viruses, so the capability of an RNA virus to insert itself into the cells genetic code is impossible for almost all RNA viruses. These viruses are collectively known as retroviruses. It’s likely the absence of latency with RNA viruses is in part due to the fact that most RNA viruses cause cell death (lysis) at the culmination of creating virons (new viruses) and also in part due to the inability of RNA to cross nuclear membrane into the cell nucleus.
SARS-CoV-2 is a RNA virus and lacks a reverse transcriptase enzyme to be able to make DNA. See the enclosed diagram to illustrate the lifecycle of SARS-CoV-2.
As part of tomorrow’s update, I’m going to try and talk about mRNA vaccines, and why mRNA vaccines are functionally unable (extremely unlikely) to be able to alter the cell’s DNA, which should tie nicely into this discussion.