HIV: Characteristics, Mechanism of Action, Prevention and... Cure?

The feared virus of HIV, the pandemic of the world, the enemy we have to fight against. But... how?

Knowing the Enemy

To start with, our enemy is a virus categorized as a retrovirus, as it has the ability to produce DNA from its RNA strand.

The HIV can be categorized as HIV-1 & HIV-2. The first one is prevalent globally and more virulent (more severe) while the variant HIV-2 is present in some parts of Africa and it is less virulent. We are going to focus on the HIV-1 variant as it is the most aggressive!

To make matters complicated, the virus has subtypes catalogized with letters. The most prevalent is M.

Their importance? They make a diverse genetic variation that allows them to escape the immune system surveillance. And to make it worse, they mix and match their genetic data forming the so-called Circulating Recombinant Forms, which make them even more impossible to kill for our body and with artifical methods.

Seriously, there is even a list of Circulating Recombinant Forms!! (thanks to the scientist group of Los Alamos National Laboratory at www.hiv.lanl.gov).

Now hold on tight because the enemy has plentiful of characteristics! However, we are going to focus on the clinically important ones.

As most viruses, we can break down and explain its clinically important parts as seen in the image:

• Envelope from the cell host membrane. This envelope has the GlycoProteins (gp) gp41 & gp120.  The former is attached to the envelope and the latter protruding outside. 
• Tegument or the space in between the capsid and the envelope. It is important as it has the enzymes of the virus like the proteases and most importantly its reverse transcriptase.
• Capsid covering the RNA, conical shape. It is formed by monomers of the Protein p24.
• RNA single stranded, positive sense. It has 3 main genes that are of importance to us.
  gag = forms the core proteins for creating the new virion (like p24).
  pol = forms the reverse transcriptase, protease & integrase
  env = forms the gp121 & gp41 for the envelope from a chopped precursor that is called gp160

The Strategy of Our Enemy

It is never present in the wild, which just makes it hard to accurately say an origin point.

The virus only comes from another person systemically. That means, sharing contaminated blood (in needles) & in sexual contact, as it is present in some secretions like semen and vaginal. The people at highest risk are people with rectal intercourse, as it ulcerates the anal area and the virus has it easier to enter the rectal arteries.

First the troops of HIV virus attach to the T helper cells (or CD4+) of the immune system by using his receptors: CD4 (hence its name) & CCR5 (receptor for chemokine). Additionally, some strains can attach to Neutrophils & even neurons, as these share the chemokine receptor CXCR4 that is attacked by the virus.

Important here is the gp120, as it is the part that anchors to the CD4 receptor and induces a comformational change that uncovers one part of that glycoprotein called V₃ loop. It is this loop that attaches to CCR5 (CXCR4). On the while, gp41 maintains it attached to the viral envelope.

After the attachment, this glycoprotein pulls the envelope and the host cell membrane together, fusing it. Now the viral troops are in!

This fusion makes the capsid available inside and now the RNA breaks out of it and directs itself to the nucleus.

Remember the tegument? Cool, because they are needed now.

Reverse transcriptase does that, reverse transcription, which is producing DNA from a strand of RNA.
Integrase... well, integrates the DNA to the nucleus of the cell!

It is this period in which the virus can prevail latent for years in our genome without showing any symptoms. It is from this point onwards in which the protein p24 starts to appear. It is the so-called window period, and it is used clinically to detect the infection if you were potentially infected. 

That is the reason why in blood tests they will show if the antigen p24 is positive or negative. Usually it is performed by ELISA.

Latency unfortunately doesn't last forever, and the viral troops are going to attack! So it is here when the virus uses our own RNA polymerases to make mRNA copies of its integrated DNA and make the proteins that form it. Finally, proteases cleave the proteins to form the structures and the virus escapes with the cell membrane of the poor CD4 cell.

What about us?

There are different stages of the HIV infection. The first ones just feel for the patient as a common cold with an asymptomatic period following. 

After this, the prognosis just gets progressively worse.

The patient enters the symptomatic stage (after virus latency) and CD4 cells (the CD4 counts) will start to drop. As T_h cells start to drop, the immunity also drops, giving rise to the opportunistic infections. This vary from fungal infections to bacterial and importantly is that for healthy people they don't even cause any harm.

The final step is progression to Acquired Immuno Deficiency Syndrome (AIDS). Immuno Deficiency = affecting the T_h cell numbers

Syndrome = group of signs and symptoms

It is worrying for a clinician as, at this point, literally any infection could kill you. The body will have no way to fight the infection!

Attacking the enemy

You know what is all of the previous viral steps were leading to. Treatment!

In each of the steps the virus can be blocked from its malicious activities with either drugs or even better: our own genome.

With drugs you can stop virtually all of the steps that lead to infection, and that is why they are so important! They go from blocking the receptors, to using analogs that block the reverse transcriptase (Nucleoside Reverese Transcriptase Inhibitors) and other of the enzymes.

The only problem with drug usage is that it does not destroy the virus as it would happen with antibiotics & bacteria. They only prevent the infection. And this will lead to the "infected" person to have Viremia indefinetly.

Vir- for virus, -emia for blood. Viruses on blood. 

So, if the patient stops the treatment, he will be infected.

But what about the people immune to HIV?

These are people that have a deletion in the gene that codes for CCR5, the CCR5-delta32. Basically meaning that they don't have the attachment point for the viral entry.

In other cases it has been reported that people will even produce Antibodies against their own cells, suggesting some type of autoimmunity.

As a curiosity, there was also a patient that was cured from HIV, called "The Berlin Patient". He was HIV+ when he received stem cells treatment for myeloid leukemia. And the CD4 cells produced by these stem cells were lacking the CCR5 receptor, thus making him immune!

The Ultimate Prevention

As you may be tired of hearing... use a preservative! That is all!

Okay... not really.

There have been developments of vaccines against the virus so we induce the formation of Antibodies IgG and IgA, which are protective.

So, how does it work?

Remember the V₃ loop in the gp120? Cool. That is what we are targetting here. What we do is give a vaccine that has extracts and different proteic combinations of V₃ loops from different strains to induce an immune response with antibody production. IgG for protection everywhere in the body & IgA for protection in mucosal surfaces (semen, vaginal secretions, and even anal). This will just not make the patient protected, but also non-infetive!

The only downside is that the vaccine doesn't work with all strains, onlt a select group of them, as there is a lot of mutagenicity from the Circulating Recombinant Forms. So still it is not protective enough to be mandatory everywhere.

Let us see what the future brings upon us in research!

War has just started.

Closing

I have been wanting to do this post since I had my finals this semester. I had so much information in my head I felt I could literally write a book!

It is finally over and couldn't have gone better!

By the way, today is my Steemit Birthday! Hopefully in the next couple of days I can post something as a celebration, or as a retrospective. I will see what can I make interesting!

Anyway, I hope you enjoyed this one. 

This is @deholt, signing off!

Edit: Fixed links & images. They should work now!

Image Sources

Images are numbered from order of apparition to not make any confussion.

1. Virus (CC0) - at Pixabay.com by RSunset
2. HIV Scheme (Public Domain) - by Drs. Louis E. Henderson and Larry Arthur. at the NIH 1994 
3. Checkmate (CC0) - by stevepb at Pixabay
4. Viral Cycle Scheme (CC BY-SA 3.0) - by Jmarchn at Wikimedia Commons
5. Virus infecting Lymphocyte (CC BY-SA 3.0) - by Waglione at Wikimedia Commons
6. People Men Thinker (CC0) - by Clard at Pixabay
7. Pill (CC0) - by qimono at Pixabay
8. Blood elements (CC0) - by Mekis at Pixabay
9. Condom Hold Sex (CC0) - by sasint at Pixabay

References

• Human Immunodeficiency Virus (HIV) - by the German Advisory Committee Blood (Arbeitskreis Blut), Subgroup ‘Assessment of Pathogens Transmissible by Blood’ at PubMed
• Mucosal IgA Responses: Damaged in Established HIV Infection—Yet, Effective Weapon against HIV Transmission - by Viraj Kulkarni and Ruth M. Ruprecht at PubMed
• Ten Years HIV Free: An Interview with “The Berlin Patient,” Timothy Ray Brown - by Michael M. Lederman and Earl Pike at PubMed
• HIV Resistant Mutation - blog by Julia Paoli at Nature
• Functions of the Chemokine Receptor CXCR4 in the Central Nervous System and Its Regulation by μ-Opioid Receptors - by Bradley Nash and Olimpia Meucci† at PubMed
• Vaccine-Elicited V3 Loop-Specific Antibodies in Rhesus Monkeys and Control of a Simian-Human Immunodeficiency Virus Expressing a Primary Patient Human Immunodeficiency Virus Type 1 Isolate Envelope - by Norman L. Letvin, Suzanne Robinson, Daniela Rohne, Michael K. Axthelm, John W. Fanton, Miroslawa Bilska, Thomas J. Palker,† Hua-Xin Liao, Barton F. Haynes, and David C. Montefiori at PubMed
• Clinical Microbiology made ridiculously simple™ 6th Edition - by Mark Gladwin, MD; William Trattler, MD; C. Scott Mahan, MD.