Welp, here is my attempt at something

For a long time, I've been carrying the information about science, specifically oncology, pathology, and molecular biology. One hurdle to overcome is the explanation of these concepts to people. Thus, this is my attempt at explaining this in the simplest terms possible. Hope you enjoy, and please tell me how simple I kept this.



Vocabulary:
Protein - A chain of building blocks called "amino acids"
Enzyme - A protein that can speed up chemical reaction
DNA - A long molecule containing genetic information.
RNA - Similar to DNA. It is used to make proteins.
Active site - The part of an enzyme where the reaction occurs.
Transcription - A process where DNA is used to make a matching RNA strand.
Inhibitor - A molecule that stops the action of an enzyme.
Nucleotide - A piece of DNA or RNA
NNRTI - These drugs work by binding to a pocket on the RT enzyme. This "locks" the enzyme and prevents transcription of RNA

Translation:
HIV-1 is a complex virus. Each step is important to its success. That is why it is a big target of anti-retroviral drugs. The first step is the infection of a suitable host cell, such as a T-cell of the immune system. To infect these cells, the cell must present a certain receptor, or "locks" on its surface. These locks are called CD4, which are shaped like hooks, and the coreceptor, which is shaped like a golfing tee. These locks interact with protein structures, which are on the surface of the virus. These proteins are the "key" of the virus. The key is divided into a ball shaped structure called gp120, and a rope structure named gp41. When HIV approaches a suitable cell, the "keys" bind to the "locks" of the cell. This is called attachment. It helps to bring the key to the second part of the lock. Once the lock is fully bound with the key, the structures move aside, and create space for the "rope" key on the virus. GP41 then unfolds, and inserts itself into the cell membrane. Then, it folds back on itself. This draws the virus and the cell together, and makes the process of membrane fusion easier.

The container carrying the payload of the virus enters the cell and breaks open, releasing two viral RNA strands, and three enzymes. These are called Integrase, Protease, and Reverse Transcriptase. RT begins the reverse transcription of RNA. It has two active sites. The "RNase H" active site, and the "Polymerase" active site. The Polymerase active site grabs the RNA and matches it with matching DNA pieces to form a RNA-DNA helix. "RNase H" breaks down the RNA. The "Polymerase" then takes the remaining DNA strand, and matches it with complementary DNA pieces to form a full DNA structure.

Now, it's the cue for Integrase. It cuts a little piece off of each side of the DNA, creating two sticky ends. Integrase then grabs hold of the DNA and integrates it into the DNA of the cell. The cell's DNA now contains the genetic information of HIV. The cell becomes activated, and this starts transcription of the viral DNA into messenger RNA. The RNA goes to the outer parts of the cell, where components of a new virus are created.

Some of these parts have to be processed by the viral Protease. Protease grabs these parts, and cuts them into smaller functioning pieces. This step is important to create an infectious virus. Two viral RNA strands and the viral enzymes then come together, and the little pieces assemble around them, forming the capsid. This particle leaves the cell, acquiring a new set of proteins. The virus matures, and becomes ready to infect other cells.

HIV replicates billions of times per day, destroying the host's immune system, and eventually causing disease. Drugs which interfere with the key steps of viral reproduction can stop this fatal process.

Entry of HIV into the cell can be blocked by fusion inhibitors.
Inhibition of Reverse Transcriptase by "fake DNA pieces", or by NNRTI's are also part of HIV regimens.
The action of Integrase can be blocked
Protease Inhibitors are also part of standard HIV therapy.

Each blocked step in viral replication is a step towards better control of HIV.

 

You explained it well, I understood the vocab and what points the video and your written part were trying to highlight. Good work.

 

Tyvm x3

 

Np.

 

Nice work.

 

I lost you at "For a long time..."

 

Bulli. D:

@Stealthyyyy :3

 

Thenk you very much x3

 

What is the purpose of this may I ask? Just practise or?

 

I guess you could say practice.

 

How confirmative.

 

*already knows most of this*

 

Well aren't you a smarty pants then. >.>

 

How can we know for shore
Oh dats right I told u lel

 

Guys, Imma try with another video next time. I have to master simplicity x3

 

Sure. ill be on the lookout.

 

Tyvm x3

 

Stahp it. :3
Go eat your noodles. >.>

 

So do most brits on here above the age of 11 :3

 

What about Aussies? :3

 

I think a lower proportion

 

Oh gee, thanks. >.>

 

I think it's true >.< might not be doe

 

Once more.
Oh gee, thanks. >.>

 

But you know it, so you're even more special!

 

.....
Oh gee, thanks. >.>

 

Second try :3



Vocabulary:
*Mutant - An organism with genes that are slightly different than their normal counterparts.
*Wild Type - An organism with the default genes.
Error Rate - This term applies to enzymes that construct DNA. The enzyme in our bodies that build DNA have a very very low error rate, which is about 1-100,000 to 1-1 million wrong nucleotides per genome copied. In this case, Reverse Transcriptase has a high error rate, using up to 5 wrong nucleotides per genome copied.
Nucleotide - A piece of DNA or RNA.
Proofreading Activity - Most DNA building enzymes such as our own have a proofreading mechanism. They have a second active site where they can catch the occasional error and fix it. In this case, Reverse Transcriptase has no proofreading activity.
Genome - All of the genes of an organism
Genotype - The genes that the organism has
Mutation - A change in the DNA genotype. These mutations also lead to a change in the amino acid sequence of a protein/enzyme.
Amino Acid - Building block of proteins.
Enzyme - A protein that speeds up a chemical reaction.
Resistance - When a drug seems to have no effect on a virus/bacteria. Resistance is usually caused by mutations in HIV.
Inhibitor - A drug that stops the action of an enzyme.
Cross Resistance - When an enzyme is resistant to many inhibitors.
IC50 - The amount of a drug needed to lower the viral count by 50%.
Adherence - The action of giving/taking a drug.
Drug Concentration - The amount of a drug in the bloodstream.
(letter)(number)(letter) - This format is used to say a mutation. Let's use an enzyme with 69 amino acids for this example. If I were to say D30N, it means that the 30th amino acid, which was Asparagine, mutated to Aspartate. Asparagine and Aspartate are just two of the twenty amino acids normally found in humans.

Now for the good part.

The ability of HIV-1 to develop drug-resistant mutants is due to two reasons. The virus replicates up to 10 billion new viruses per day. And the high error rate of Reverse Transcriptase when copying the viral genetic code.

Up to five wrong DNA pieces may be used per genome copied. RT has no proofreading activity, a mechanism where wrong nucleotides are not noticed, and used as a template. These errors lead to a change in the viral genotype.

Statistically, every possible single mutation in the HIV genome occurs many times per day. Mutations in the gene that codes for the viral enzymes, result in the making of enzymes that are quite different from their wild type counterparts.

The activities of the wild-type enzymes are normally blocked by HIV drugs. However some mutations cause changes in the amino acid order, which lead to drug resistance. The location and the pattern of the mutations determine the severity of the arising resistance. For example the mutation (Asparagine)30(Aspartate) in Protease, may cause resistance to only one specific Protease inhibitor. Whereas mutation I54V (Isoleucine)54(Valine), may cause resistance to several Protease inhibitors. This is called cross resistance.

With second generation (improved) drugs, resistance is less likely to develop. They need much more mutations to accumulate before they become useless.

As a consequence of resistance, the IC50, the drug amount needed to lower the viral amount by 50%, is higher in the mutant virus compared to wild-type. The difference in IC50 between wild-type and mutant virus is called "Change in IC50".

Because most mutations decrease the "fitness" of the mutant virus, if no drugs are there, the normal virus dominates the population. Mutants still pop out, but mutated viruses are less "fit", and persist only at low levels. Starting drug therapy puts the virus under pressure, and the viral load decreases. If a drug were given alone, mutants would emerge within a short period of time. Since they are not affected by the drug, they would come to dominate the viral population, and the treatment fails.

That's why doctors combine at least three drugs, to target HIV simultaneously. Multiple mutations in different enzymes would be required for resistance to all drugs in the regimen.

Once the viral population is driven down to undetectable levels, the chance of a mutant virus emerging is reduced dramatically. High levels of adherence are required for successful HIV therapy. Sub-therapeutic (not enough) drug concentration due to poor intake leads to a higher virus population. This makes the chance of resistance arising higher, and treatment failure.

Improved drugs combined ease of intake, and high potency against mutant viruses, to help patients control the HIV infection.

*inhale* PHEW
Did I do good? :3

 

Yes you did.

 

Another one of these bots.

 

;-;

 

Nerd.

 

You guyz are bullisss

 

No problem

 

Lmao four people voted no.
Need more practice :/

 

Face it Mlg, you are too much of a nerd.













Jk ily <3

 

:3

 

:3 :3

 

You two should just date and get it out the way :-C

 

Hmmmmm....

 

jk lmao
but U WOT M69

 

Like you and @smeags :3

 

I do believe I find the attraction only towards females.

 

Hahah, so funny :3

 

@smeagzyyyy
Aw, it doesn't exist

 

DiamondProGamer doesn't either ;(

 

You know you wanna

 

Calm down xD. I know you dream of that but eewwww bruh.
I do believe that is why Google exists...

 

Nope, I already have a bf.

 

*Stealthy's fingers were crossed*

 

*Walks away after listening to conversation fearing for these people's mental health*

You did good by the way MLG. :3

 

Liar liar pants for hire. *Spongebob reference*

 

Tyvm x3

 

Aww mlg why dids you have to use language for the lower consensus I wanted to learn about neurological impulses and adaption.
Ps half of my family are neurologists or work in neurology.

 

Mlg I'll post an essay on the perpetual state of mind we call reality. Lets see if people know any little thing about quantum physics and quantum reproduction

 

Do it.

 

And be subject to the scrutiny of myself and yourself, quite knowledgable I would hope in the field

 

Depends on how knowledgeable he is.