During the covid pandemic I’ve been learning about dynamic systems in biology from a textbook, Physical Models of Living Systems[1]. This book has illustrations by David Goodsell! Some notes from Chapter 1:
- HIV was initially thought to be a very slow virus, because it might remain in the system for ten years before showing symptoms
- an alternate hypothesis is that HIV is growing very fast, but the immune system is fighting back at the same rate
- if the only thing you measure is number of virus particles you can’t tell the difference between {it’s not growing} and {it’s growing very fast but also shrinking very fast}
- a trial for a “protease inhibitor” drug that stopped replication would show the difference — if it’s {it’s not growing} then the drug would show no difference in the number of virus particles, but if it’s {it’s growing very fast but also shrinking very fast} then the drug would stop the growing very fast but not stop the shrinking, and the total amount would rapidly decline
- the total amount rapidly declined, but temporarily
- in asymptomatic patients, HIV is producing a billion new virus particles per day
- the virus mutation rate is high, and generates all possible one-letter mutations in a few hours (!!)
- the “cocktail” drugs that are now used work because one drug might stop one-letter mutations (??I don’t get this??) and two drugs might stop two-letter mutations but three-letter mutations are so rare that three drugs can stop all the three-letter mutations too
- virus particles are called “virions”
- there are RNA viruses, DNA viruses, and “retroviruses”, which contain RNA but then convert it to DNA to infect the cell
- “reverse transcriptase” is what converts the RNA to DNA
- “integrase” is what inserts the virus DNA into the host cell DNA
- “protease” cuts a long protein chain into multiple proteins; the long one (“polyprotein”) doesn’t actually work, but contains multiple proteins, like a tarball; protease works like
tar xf, splitting the polyprotein into the final proteins; in non-viruses, proteases do a lot of different things[2] - anti-HIV drugs included “inhibitors” to stop reverse transcriptase and protease
- the immune system is fighting infected cells, and also virus particles
- model: each time step,
- some fraction of infected cells cleared out
- virus particles turn some uninfected cells into infected cells {without antiviral drug}
- some fraction of virus particles cleared out
- infected cells produce some number of virus particles