HIV Strains
What is 'mutation'?
A mutation, first of all, needs to be understood as a genetic change in some genome. A genome is the genetic composition, the genes, of an organism. Like we have a genome, a human genome, that varies among us in minor ways. So a mutation in one or more genes is simply a genetic change in the gene, any particular gene. It may be a single nucleotide which are the building block of making the gene or genome. It maybe be just one or several or it could be a recombination between two different genomes that have areas of commonality so they can kind of hitch up together and it's called recombination; that's a genetic change. Or you can have a deletion or a segment is lost in the deletion of a gene; you can have a duplication. All kinds of genetic changes can occur.
What is 'HIV mutation'?
When we talk about it with HIV, we're principally interested in a mutation, a genetic change in that can change the behavior of the virus so that it is no longer susceptible to a given drug. If the drug is targeting the enzyme called protease or another enzyme called reverse transcriptase, an enzyme that makes the reaction RNA to DNA, then you'll have a mutation in those genes that the drug can no longer inactivate that enzyme; the enzyme is still active in the presence of the drug because of the mutation. But of course mutations can do other things. We, in studying pathogenesis, how the virus causes disease, are interested in mutations in this or that gene of the virus. Does it change the pathogenic events? Is there a mutation or a genetic change that leads to more ease of transmitting the virus? If I'm the virus am I more infectious because I made a mutation in this or that gene? So it's not just about drug resistance it's about many things. It's about any property you want to talk about.
What is 'HIV strain variation'?
You can look upon it almost as a continuum of genetic change. Some are transient and others are fixed in the population. Within HIV 1, there are groups that stay within a population that are given alphabetical letters to type. So in the United States and in Europe, it's B. What does that mean? If you look at all the people infected in the United States and all the people infected in Europe, they have B, for the most part, almost always. But if you look at it, they're all different. Yet it's all B. That's why the only man's and scientist's arbitrary definition, that if you're this close, then you're B. But there are all variations of B. A much bigger jump is if you jump to C, which is the dominant virus in South Africa. And it has some important biological differences, very important biological differences. It still causes AIDS with efficiency, as does B, but there are some very important differences between B and C. Significant for the epidemic, yes. Significant for therapy, yes. So we can't just say HIV is HIV even biologically with its properties. That makes the problem complex. So B and C are different, let's call it, strains. But within B and C are a whole host of variants. If we all had B in this room, we would all have a different -- you see, it gets into terminology. We call these things clates. That's the scientific term that was chosen between B and C. That's a clate. But now we'll talk about within Clate B all kinds of strains and variations. Then within any isolate from an individual, there are mircovariants, and they are endless.
Will more strains of HIV appear in the future?
Yes, by recombinants especially, there will be. I don't think it'll be, I hope, not much more than we have now. Every variant that's possible has occurred, but there might be more recombinants that establish themselves within a population. And it's possible that existing ones will come to new lands, as has already occurred multiple times. We have so far been lucky to not have a different, new clade here. For example, clade C is not here in America. Would I be shocked if it were in five years time, that we had a lot of people infected with clade C? No, I wouldn't be shocked. But I can't predict it.
How do the different strains of HIV affect the progression of AIDS?
Clade C almost always only has variants that use the receptor on the cell surface known as CCR5 -- after CD4 -- CCR5 -- it gets in that way and that's enough to cause AIDS and do it earlier than we see AIDS in the United States. Is that because of genetic reasons, environmental reasons, or viral reasons is not 100% certain that the virus doesn't contribute to that. It probably does. But in Clade B, often microvariants will emerge that use a new receptor called CXCR4. Those microvarients tend to be more virulent, more pathogenic, more disease-causing than the original ones that use CCR5 in Clade B. But if you go to Africa you never see the CXCR4 emerge almost ever. The original CCR5-using variant is enough and then some.
Are different strains of HIV transmitted differently?
That is not clear to the best of my knowledge. All HIV's can be transmitted by the same pathways there may be subtle differences in the magnitude of one being able to go via lets say vaginal heterosexual transmission verses another. But in my mind that's far from being established yet.
Is it possible to be infected with HIV more than once?
Sure, it's unexpected but it does occur and has been documented that you have different strains infecting the same individual. And that's a recombinants or that's why you get A, B, C, D and all these recombinants we talked about before. Cause you have different strains infecting, different clade viruses infecting the same person.
Do medical treatments work against all strains of HIV?
Pretty much, right now, the mechanisms are the same. We have agents, or drugs, that target the enzyme called reverse transcriptase. We have drugs that target the enzyme protease. Both are from viral genes, coding for these proteins that are viral specific, that are needed for the virus to reproduce itself. It works across with all clades that I know of. We may be learning that some are more resistant to this or that drug. That's the kind of things that we need more experience yet before being definitive about that. In the future, integrase inhibitors are coming very soon. That's another enzyme encoded by the viral genome that is necessary for the virus to integrate its genes. So far I don't know of any clade differential in that, in any strain of HIV that is more resistant from the start to that. There may be differences in how rapidly one gets resistant to it, but there's not enough time to test that. And finally, we have a class of inhibitors that are blocking HIV entry that are being studied now. And there is reason to believe that that could depend on the clade because of the different receptor uses.