Two weeks of breeding and feeding the virus! : Part 2

Every human being has a reservoir of cells of the immune system (T-cells and B-cells). These cells usually are in a virgin state; that is, they would not have encountered any infectious material; therefore do not know anything about any organism. These reservoirs are called lymph nodes. The ones we are most familiar with are the tonsils and those on the inner side of your thighs which when you have a wound on your leg are also painful (mwandabvu)

The constabulary of the immune system (dendritic cells, macrophages, langerhans cells) swim to these lymph nodes which act as the Central Police Station. I want you to visualize this setup. In this police station are the Detectives or CD4 (T-Helper) cells which before the entry of the constabulary are relaxed and do not know that such thieves as the one held by the constabulary cell exist. There are also amateur recruits that know only to deal with a single kind of crime each (B-cells). If they are programmed to deal with thieves, when they meet murderers they just leave them.

Now, when the Constabulary gets into the Police Station with the thief, the new recruits (B-cells) rush to scrutinize the thief wanting to check if he/she falls within their specialty. Once it is discovered that indeed it is the one; that B-cell swallows the virus and continues to bash it with chemicals until the proteins that make up the outer coat of the virus are degraded to just small chunks called peptides. If we were to continue with our example, these B-cells would, instead of going to the Detective with the thief, they would rather chop the thief into pieces then present maybe the leg or the buttocks and say "All cellphone thieves have this kind of legs or buttocks; so what should we do?”

The Detective scrutinizes the leg and if he is satisfied that indeed the thieves bear such features, he simply sends a directive in the form of chemicals called cytokines which tells the new-recruits to unleash all the dogs they have and to wake up all the other recruits who could be sleeping. These dogs would also be programmed to only catch those people with specific features and they are called Antibodies.

So B-cells function to produce antibodies that are specific to HIV. These antibodies now bind to the outer coating of the free-floating virus thereby alerting other cells that “Here with me is a foreigner called HIV”. This is called tagging. Once the tagging is successful, the free virus is then swallowed by macrophages or the virus is destroyed by another way which I think is beyond the scope of our discussion but for your benefit is called the Complement system.

Here the CD4 cell functions to amplify the B-cell response.

The antibodies are what people at the HIV testing centers would be looking for. If you have them it means that your body was once challenged by the HIV and it responded by sending out these markers to detect the virus and usually they begin to appear in detectable quantities after 2 weeks. That is why when you are exposed to the virus and you go for testing they ask you to return after 2-3 weeks.

Generally what I have described above is what happens when a person is infected by any foreign agent. Usually, the body is successful in eliminating the infectious material in this way but when it comes to HIV, there are many complications that the body encounters.

Unfortunately, when the Dendritic Cells or Langerhans cells capture HIV at the point of entry and begin to bash it, the virus releases its genetic material (RNA) . Now, the virus has an enzyme(Remember Form 1 Science: An enzyme is a substance that is able to speed up a rection or process!), this enzyme is called Reverse Transcriptase and its function is to assist the cell to form DNA(normal genetic material in living cells) from RNA(the viral genetic matter.) This process is called Transcription.

Once this DNA is inside nucleus of the cell it begins to be integrated into DNA of the host cell. I hope you know that the purpose of the DNA is to direct the cell on what kind of proteins to make. Now because the cell now also has the viral DNA, it also begins to make viral proteins. At this point viral replication begins. So, I hope you have realized that when the Constabulary captures the virus he is fooled into beginning to make more viruses before he reaches the Police station. By the time our beloved constabulary reaches the police station he would probably have produced thousands more HIV particles. That’s how smart HIV is and how foolish our bodies are!

Now, to make life even difficult for our bodies; this HIV has got a great affinity (liking) for the CD4 glycoprotein that is found on all CD4 positive cells (T-helper cells). Once it binds to such a cell it is swallowed and the cell goes haywire and begins to produce viruses. So the cycle continues.

Remember we once said there are other T cells which are not CD4 cells but are CD8 cells (T-cytotoxic cells). Their function is to kill any infected cells. So once they come in contact with any CD4 cell that is infected, it is immediately killed or is influenced to commit suicide. HIV can also influence CD4 cells to bind each other resulting in their death. (Syncytia formation).

That is how HIV infection reduces the CD4 cells in our bodies and that is why CD4 cell monitoring is important because it tells us the state of our immune system. A low CD4 cell count signals the need to boost the immunity or to reduce viral multiplication.

If you are an HIV-patient: do not forget to regularly monitor your CD4 cell count. If you are taking care of an HIV-positive relative---Don’t let it until too late to have his/her CD4 count checked.

Lets meet in the next topic: HIV does not kill, it facilitates death!

Two weeks of breeding and feeding the virus! : Part 1

In the first two articles we noted how HIV penetrates the vaginal or penile mucosa (skin), we also discussed the risks associated with Oral Sex. These are not the only routes of infection: we have direct injection of infected blood like in cases of needle-stick injuries, we have mother-to-child transmission during pregnancy and we also have anal transmission in homosexuals and those who engage in anal sex. It has been proved that anal (rectal) exposure has a greater risk than vaginal exposure but both have a much greater risk than oral exposure.

We also noted that both the foreskin and the vaginal mucosa are rich in cells called dendritic cells whose job is to capture any foreign object like bacteria and viruses. In our quest to follow the path that the Human Immunodeficiency Virus takes until somebody reaches full-blown AIDS let us examine what happens from here.

Before we jump into this, as aspiring virologists we also have to know how the blood is constituted. So for a short period we are going to be hematologists (somebody who studies blood!). This red fluid we call blood contains cells. Red blood cells (erythrocytes) give it the red color because of a chemical called hemoglobin whose function is to trap oxygen from the lungs and deliver it to other cells so that we can produce energy. We also have white blood cells whose function is to protect the body from infection. We have platelets which help in clotting when we bleed. Finally we have the fluid called plasma where everything swims in. One milliliter (1ml) of blood has about 6 billion red cells, 3 million white cells and 1,5 million platelets.

We are more concerned about the White Blood Cells (WBC) because we are worried about how a person can suddenly become frail and fail to defend himself from diseases. These WBC can also be divided into Lymphocytes (because they are associated with lymph nodes) , Granulocytes (because they have granules) and Monocytes ( because they have a single big nucleus). Don’t worry about the big names, they are only there to confuse you, I will explain to you what they all do.

Let us continue with the series and see how lymphocytes are subdivided. The family of lymphocytes is further subdivided into B-cells and T-cells. The “B” refers to a part found in birds called bursa of Fabricius where they mature, in human beings they are produced in the bone marrow and then move to the spleen where they mature. The T cells mature in the Thymus hence the “T”.

In HIV Sciences we are more concerned about this T- cell family and we will basically concentrate on them. However, I promised to explain the basic functions of Monocytes and Granulocytes. Monocytes are a family of white blood cells which swim in the blood looking for any damaged tissues. When they find this tissue they undergo a series of changes that result in them being called macrophages. These macrophages can engulf and digest any bacteria that may want to enter through the damaged tissue eg a wound. Their behaviour is similar to dendritic cells( Langerhans cells on the foreskin). When there is a wound and the bacteria is seeking to enter the body; macrophages and the injured tissue produce chemicals which call on Granulocytes to come and reinforce. These Granulocytes like Monocytes and Macrophages are able to swallow infection agents like bacteria.

Back to T-cells. How many of you have heard somebody saying “He is critically ill, actually his CD4 count was very very low?” Next time you hear them say CD4 blah blah just ask them , “You mean T-Helper cells?”

The T-cells are further categorized into T-Helper cells and T-Cytotoxic cells. The function of the T-Helper cell is to help the body to defend itself by stimulating other cells into action like the B-lymphocyte mentioned above. The T-cytotoxic (“cyto” means cell thus toxic to cell) assist in destroying other infected cells.

You see, on these cells there are certain clusters of glycoprotein (a protein coated with some sugar) attached to the outer surface. Now some Scientists decided to differentiate these clusters of glycoproteins by using numbers. So T-Helper cells carry one of this glycoproteins whose Identity Number is 4 (four). The complete name becomes Cluster Differentiation 4 or CD4 in short. Now just like we say a patient who has HIV infection is HIV-positive; we can also say a cell that carries a CD4 glycoprotein is a CD4 positive cell. That is why T-Helper cells are called CD4 cells and T-Cytotoxic cells are called CD8 cells. Just that!!!!!!!!.

We are now done with the hematology of HIV Sciences back to our beloved virus! The virus is now engulfed by the dentritic cell (Langerhan)or Macrophage . The behaviour of these cells is typically that of a Constabulary Policeman in Zimbabwe: when he catches you he beats you until you soften up and then he parades you to the Officer-in-charge; No Negotiations! These cells engulf the viral particle and begin to bash its outer coating with acids called lysozomes which are found within these cells. The ultimate goal is to present this intruder to the officer-in-charge who in this case is the CD4 (T-Helper) cell.

……….to be continued…………………..

Oral Sex: Who can eat HIV and survive!

Last time I dwelt on how HIV infects the vaginal or penile walls. A question that is always hovering in many discussions is whether HIV can be transmitted through oral sex.

First of all we need to understand that oral sex can be classified as receptive, meaning the act of inserting one’s penis into another partner’s mouth with ejaculation and also non-receptive meaning without ejaculation.

Is HIV transmissible without ejaculation?

There are studies which have shown that HIV can be transmitted through the anal route without ejaculation, however the cases that have been reported are very very rare. This is because it has been difficult to engage in studies where the subjects are controlled from ejaculation. Thus, it remains hard to clearly conclude whether HIV can transmitted orally without ejaculation. Please do not take this as a go-ahead to engage in unprotected oral sex because it has been proved that pre-cum also is potentially contagious!

… but what of receptive oral sex?

There is reasonable scientific evidence that HIV can be transmitted through receptive fellatio (oral sex). It has been shown in monkeys that if you expose their tonsillar tissue to SIV (Simian Immunodeficiency Virus which is nearly the same as HIV), the monkeys can be infected.

Data is also there about the histological make up of the animal tissues of the tonsils. The histology of the tonsillar tissue is identical to the histology of the vaginal and rectal tissue with high density of dendritic cells (which we talked about in the previous post) and M-cells which are also capable of transporting antigens (or viral matter) to lymphoid tissue resulting in infection.

This is just scientific evidence but it has been hard to actually pinpoint receptive oral sex as a major transmission route. This is so because, most people do not practice oral sex in isolation but mostly in conjunction with other riskier practices like receptive anal and vaginal sex.

Epidemiological studies have classified the risk of receptive oral sex as low, however the risk increases significantly if there are injuries to the mouth or in cases of oral thrush.

Let me end by saying, swallow the sperm at you own risk! Let’s meet in the next topic:
Two weeks of breeding and feeding the virus!

Apologies: I am in Zimbabwe

Dear all

I am in Zimbabwe, my laptop has no battery; there is no electricity. I cant write anything; so it would be hard for me to update this blog within the next few days.

Please bear with me. Thats our Zim for you.

Stay positive and responsible

Freeman

What really happens during and after unprotected sex with an infected partner!

I chose to begin this series with this topic because I feel we need to move step by step. We need to trace the life cycle of the virus sequentially so that we can be able to understand what really happens when one gets infected and later on be able to appreciate the current targets of treatment. Thus, first things first: SEX!

When Jacob Zuma took a vigorous bath after having sex with an HIV positive woman, did it or didn’t it help? I hope by the end of this article we would have been able to at least make a decision on this method of prevention.

Before we jump straight into the scientific pool, there are a few points that I want to make. Firstly, I want to define a virus. A virus is a very small particle that cannot be seen by a naked eye. A virus is not a bacteria however they both are not visible to the naked eye although it is very possible for us to see bacteria (like cholera bacteria or Tuberculosis bacteria) using a simple microscope found in hospitals. Most viruses are more than a thousand times smaller as compared to bacteria thus we need highly specialized microscopes called electron microscopes to see them (in Zimbabwe there are only two such instruments).

Secondly, unlike bacteria, viruses are non-living things. They do not use energy for respiration, they cannot multiply on their own, and they cannot manufacture anything for themselves. So how do they survive? Ha ha ha, they are not alive; when a virus is outside a body it is as useless as the soil. How do they multiply? Here is the tricky part and I want you to understand because this forms the backbone of virology. Once you understand this you just become a virologist!

A human cell has at its core, genetic material that has got information which makes us different from each other. It is this genetic material that makes me different from Usain Bolt or Robert Mugabe and it is called DNA. This DNA is also responsible for storing the information about which proteins to make. Now, when HIV comes in contact with a human cell, it can be sucked into the cell, and through complicated mechanisms which we will talk about later, be able to attach its viral matter to the cell’s genetic matter. At that point, the cell will have information about human DNA and viral DNA. The cell is unable to differentiate between the information contained by this compound genetic matter thus it just starts to manufacture proteins regardless of whether they are for body use or they are viral proteins. That is how HIV abuses our bodies to its advantage!

A question that I want to ask before we begin is; why is it that shaking hands with someone who is HIV positive does not spread the virus? Or why is it that if one inserts his finger into the vagina he does not get HIV yet if one inserts his penis there is risk of transmission?

The answer lies here. The skin is made up of keratinised, stratified squamous epithelium, what this simply means is that, the cells that make up the skin are layered on top of each other like bricks, then they are cemented together by a chemical that our bodies produce known as keratin. This makes the skin hard to corrode. So even if one puts his finger in the dip-tank of HIV he will not be infected unless it’s bruised or has a cut.
The penis has got a shaft, the inner and outer surface of the foreskin and a urethral duct which passes urine. The skin that covers the shaft is as hard as that of the whole body and therefore protects against HIV infection. What we need to understand is that, the inner mucosal surface of the foreskin is not as hard as the outer skin. This part is heavily populated by cells that are called Langerhans’ cells.
During sex, the foreskin is usually pulled back so that the entire soft tissue is exposed to the walls of the vagina. The purpose of the Langerhans’s cells is to defend the body against any infective agents that may enter through the penile route. So, once there is slight friction, the soft surface is exposed and if it so happens that the woman is HIV positive and is secreting viral particles in her fluids there emerges a chance that HIV may attach to these cells.

These Langerhans’ cells have got a special receptor called CCR-5 which has got a great affinity for the HIV proteins. Once, a CCR-5 receptor attaches to HIV, the virus vomits its genetic matter into the cell. The Langerhans’ cells, as good as it is at its job of capturing tresspassers and carrying them to the guillotine; will then carry the viral matter inside itself whilst starting to make viral proteins on its own. The duty of the Langerhans’ cells is to present the HIV to the white blood cells that are supposed to be able to once and for all deal with this threat. Unfortunately, Langerhans will present viral matter to the CD4+ white blood cells which also suck the virus and become infected too!

The vaginal tract is also the same as the foreskin in terms of concentration of the Langerhans’ cells. What should be noted is that semen in infected people contains both free viral particles and more than a million white blood cells some of which would be infected. So there is possibility that when a man ejaculates into a woman because of greater contact time the woman might be at a greater risk than a man. Scientifically however, it has not been conclusively proved to be so as the results vary geographically with Africa showing approximately equal per-act probability of infection between men and women.

So, can Jacob Zuma’s method be trusted? Well, this one is tricky in that like I said the virus is not a living thing and cannot be killed by a detergent so don’t think Lux can kill HIV! Secondly, even if one washes his hands thoroughly with water, bacteria (which is bigger than HIV) will always be present, so how confident are we that thorough rinsing can remove all the millions of particles attachéd to your penis? Finally, it has been proved also that HIV infection is dependent on the amount of HIV (size of inoculum) that one is exposed to; so maybe by bathing one can reduce the number of particles attached to the mucosa but HEY DO THIS AT YOUR OWN RISK!

Having learnt the above, it does not need a virologist to realize that ABSTINENCE remains the best form of protection, followed by Single Trusted and Tested Sexual Partner then Consistent and Correct use of the CONDOM!I love you all and hope you enjoyed get ready for the next topic: Oral Sex: Who can eat HIV and survive!

Back with a Bang!

Dear Friends.

I have decided to resume maintaining my blog (http://hivscience.blogspot.com). As you might have noted, I had stopped in 2006. Then I had realized that most of the things I was writing about were purely scientific with no major help to the generality of the people.

Ever since 2005, I have been working with HIV/AIDS patients and I have realized our knowledge of this virus and the conditions associated with it, is still limited. It remains my view that if people get to understand what HIV is and what it does to the body they may be able to understand certain aspects related to HIV/AIDS better and be able to change certain behavioral tendencies that may be unsafe to them.

In all my postings I will try to be patiently simple. I will try to explain scientific concepts in a manner that will be captivating to the ordinary person without dwelling much on the big words.

Finally, It would be helpful to have a mutual relationship with the readers of my blog, thus I open the door for questions and contributions. For those questions I cannot answer, I will refer to my fellow researchers and professionals.

I will be posting articles bi-weekly; on Mondays and on Thursdays. This Thursday look forward to my first posting: What really happens during and after unprotected sex with an infected partner!
Looking forward to being with you on this train!

Regards

Freeman

HIV Genome

The HIV genome is made up of three genes that code for inner core proteins, envelope proteins and functional proteins (i.e. viral proteins). These are named gag (group antigen-since the antigenicity of this inner core is conserved through out the group, env (envelope) and pol (polymerase) gene which codes for Reverse Transcriptase which has both polymerase and ribonuclease activity. It also codes for other enzymes like integrase whose function is to facilitate the integration of viral DNA into the host cell chromosome and protease which cleaves precursor proteins into smaller functional fragments-the envelope glycoprotein is made as gp160 but is cleaved to form gp120 and gp41.



As with other retroviruses, HIV has at the end of its genome a segment of nucleic acid called LTR (Long Terminal Repeats) which are stretches of DNA that do not by itself code for any protein but functions as a regulator to the expression of the three structural genes, a function that is augmented by other genes called regulatory genes.



Regulatory Genes

These regulate the production of viral proteins: one regulator speeds up protein synthesis, another speeds the production of only some kinds of proteins and a third represses protein synthesis. Each regulatory gene encodes a protein that interacts specifically with a responsive element which is a sequence of nucleotides within the genome. Regulatory genes act in trans because they exert at a distance, the responsive sequence affect adjacent genes hence act in cis. Through their influence regulatory genes can effect an explosive viral replication, moderate growth or quiescence.

The tat Gene

That tat gene (Trans-activator of transcription) is both unusual in both structure and effect; it occurs as two widely separated sequences of nucleotides. The gene starts from nucleotide 5831 to 6045 and then 8379 to 8424.

This gene is translated to a polypeptide called Tat. This protein when bound to the viral RNA boost the expression of viral genes. It interacts with a kinase that is involved in the phosphorylation of the carboxy-terminal which encode a protein which when bound to viral RNA boost the expression of viral gene domain (CTD) of RNA polymerase-II required for initial transcription. To exert its effect the tat protein is dependent upon a short sequence of nucleotides known as TAR (trans-activating responsive sequence). Tat stimulatory effect extend to all viral proteins, it also positively feeds back upon itself resulting in enormous synthesis of viral proteins. It activates the expression of TNF-β, TGF-β but down-regulate other cellular gene expression including bcl-2 and the chemokine MIP-1α.


The rev Gene

A second regulator gene rev (regulator of expression of viral-protein) also exists as two widely separated nucleotide sequence, one from 5 970 to 6 045 then another from 8 379 to 8 653. The gene encodes a 13kD protein Rev which enables the integrated virus to produce selectively either regulatory proteins or virion components. It acts as a genetic switch whose role is in the activation of the virus from latency to active viral replication.

The vpr Gene

The gene is found between the 5 559th and 5 795th nucleotide. It encodes a Vpr protein. The protein is incorporated into viral particle. Approximately 100 copies of vpr are associated with each virion. This is mediated through specific interaction between the carboxyl terminal region of p55 gag which corresponds to p6 in the proteolytically processed protein. It confers the ability of HIV-1 to infect non-dividing cells by facilitating nuclear localisation of the pre-integration complex. This NL is distinct from the prototypic NLS because there is no negative feedback, but the NLS peptide can inhibit the nuclear localisation of other proteins containing conventional NLS eg matrix (p17) protein. It also affect cell division- all cells expressing vpr accumulate in the G2 phase of the cell cycle; vpr expression prevents activity of p34cdc2/cyclin B complex an activator of the cell cycle important for entry into mitosis.

The vpu gene (6062-6310)

Vpu codes for a 16kD polypeptide- an integral membrane phosphoprotein localised in the internal membrane of the cell. It is expressed from mRNa that also encodes for envelope proteins but translated at levels ten times lower than that of env. A complex gp120/CD4 occurs in the endoplasmic reticulum but vpu degrades the CD4 molecule because this complex interferes with virion assembly.

The vif Gene (5 041- 5 619)

Codes for a 23kD protein which is responsible for the replication of HIV in the peripheral blood lymphocytes & macrophages. Other cells have complimentary proteins to vif hence not needed.

The nef Gene (8 797-9168)

The Nef gene (negative –regulator factor) encodes a 27kD myristylated protein which is the first viral protein to accumulate to detectable levels in cells following HIV-1 infection. The protein down-regulates the expression of CD4 by infected cells by stimulating CD4 endocytosis and lysosomal degradation by interaction with the dileucine repeat sequence contained in its membrane proximal region. Also down-regulates cell-surface expression of MHC-1, this is the protein that is responsible for the perturbation of T-cell activation and stimulation of infectivity.



© freeman Chari 2005