Section 4: Retroviruses, Biomarker
Nancy Klimas Lecture
Section 4: Retroviruses, Biomarker
When we talk about latent viruses, this is what were talking about. The guy on the top is a quiet little white blood cell hanging out doing nothing because no one has asked him, it doesnt have a job yet. If it becomes activated, its because something floated into the system, some antigen, some bug that its supposed to respond to. And in our systems we have hundreds of millions of these little quiet cells and each individual cell only knows its one little job.
Now this ones for Epstein Barr, that ones for Staph, and that one is for some other bug. If that bug comes into the system, then that cell is the one that gets activated. And if it had hidden inside it, in its DNA like over there, if it has inside it this little piece of virus fragment, sitting in that DNA, that cell is turned on to make all of its stuff it knows how to make. It got activated. Its going to make cytokines, its going to make interleukin 2, its going to make ?? , oh and by the way, its going to make that sneaky little virus that was tucked into its DNA too. And thats what happens.
These latent infections just sit around doing nothing until that cell is activated and then boom, they start making virus stuff. Retroviruses are funny because were just chock full of them. We have little bits and pieces of retrovirus all in our DNA. Talk about evolution, our great, great, great, great, great, great, great grandfathers got infected with some little piece of something, maybe a chunk from a mouse back then. But its not a whole virus. They have just little bits and pieces, of bust up pieces of retrovirus tucked in the DNA. We think its an important part of the way that we evolved. That we borrow DNA from other species this way and we transfer things around. If viruses carried little pieces of information into the genome back then. And some of it was bad and that didnt work out. And some of it was good and it carried on or it was neutral and it carried on.
But there are some retroviruses that can be carried generation to generation as a whole and complete virus tucked into that DNA or rather enough DNA to make a whole and complete virus when its turned on. And this is one of those retroviruses. It can be transferred generation to generation or whats called vertical transmission, mother or father to child through the DNA. So we dont know if theres 3 or 4% of background. Theres just people who have vertical transmission or if theres some way that you can infect people back and forth in life. We dont know that at all, okay?
But we do know that this virus is one of the ones that is vertically transmitted. We know that from the mouse data. So it can be transmitted vertically. So the question is if you have children, do your children necessarily have it? And the answer is maybe yes or maybe not. First off, theres two parents not one. And each only give half of the DNA, yeah, right? So in any given child, theres only one chance in four that you can pass on any particular piece of DNA on a good day. So you dont worry too much about kids flat out that way. And then you say: And oh, by the way in their life, they have to come across the thing that activates the virus and turns this whole mess on. And so theres a whole lot of reasons not to get all worried aboutI mean Im not saying it couldnt happen to your childrenOf course its conceivable. But whats exciting right now is were getting this, were getting the understanding of it, and well probably, knock on wood, that we will be to the position where were actually intervening effectively before it becomes a bigger worry. But, um, I dont know about kids. Im saying it is a vertically transmitted virus.
We dont know if its sexually transmitted. I will say that there are sexually transmitted retroviruses. We know HIV is, obviously, is a sexually transmitted retrovirus. But, theres noyoud think in 25 years, we would have seen massive numbers of spousal pairs. And we have not. You occasionally do, occasionally we do see a spousal pair. It happens. But almost always those people both had acute infection at the same time at the onset and its really unclear if it was transmission between the two of them or if they had some other thing happen that kicked off the whole, the whole thing. And you see household Chronic Fatigue. I mean I do see mother-daughter, father-daughter, father-son, whateverIve seen it. But, in my clinical practice in the 25 years or so, its not very common. It doesnt happen a lot.
So, the next slide. This virus is not HIV. A lot of people panicked when they heard this. This virus really is not HIV. Its in the same family, but its a distant, distant cousinvery very distant. And its not infecting or affecting the same cells. So, its not doing the same immunologic thing that HIV does. Okay?
There are also other retroviruses that dont do anything that we know about. Theres a virus called HTLV-2 that I have studied myself in the past, and many others have, and its just sitting around doing nothing. Its reallyits vertically transmitted, it even replicates, and it doesnt cause much in the way of illness. So, that doesnt necessarily mean that just because you find a retrovirus, its definitely the deal. And not every retrovirus is big and bad and ugly. Theres another virus called HTLV-1 thats vertically transmitted and does cause an illness. And it causes a neurologic illness. And so, we have different bugs, different things.
HIV is a retrovirus and theres at least 20 or more drugs directed at HIV. So, will those drugs work to control this virus? That is definitely the big question of the day. And the first thing to say is: some of them probably will. And the second thing to say is, but not all of themyou couldnt just pick a random one and try it.
This ones to show you mouse going to peoplethat basically it started out way up there as a mouse thing. Mice learned to live with it. They dont have a receptor that allows this virus to become a big bad deal. So, mice just sit around for generations and generations of mice being a reservoir of virus, but not actually getting sick from the virus. But then the virus shifted and it became capable of jumping from species to human.
So, this was the study. They had in their freezers samples from people that werent from their cohort. So, these were not just Reno samples. There were samples from Florida, from California, from North Carolina, and other places. Everyone in their repository had a Chronic Fatigue diagnosis. The mean age was 55. There was two thirds women. They had this large control sample. They lookedand they looked at these patients, out of 101 patients, and they looked at the DNA, the sequences of the virus in the DNA. Its really a sophisticated way to look and they found it in 67% and in 3.75% of the 320 controls.
Now of the negative, these 33 negatives, they went on and looked in other ways. And they found 19 of those had antibody in their plasma, so that was more than half of those negatives. But this is the big number: 30 of the negatives had virus they could identify by taking the serum of those cells, the serum from the plasma, and infecting a cell line and then growing the virus in that cell line. So they could transfer from the plasma, virus to the cell line. Now that has a lot of implications and its certainly the reason why, in part, the CDC, the NIH, and others that really care about the blood industry are looking long and hard at this. They found the virus, a transmissible virus, in the plasma and they were able to infect cell lines. So it is suggestive of an infective component, at least in the blood. And then there were other ways, so they worked out that they were able to find 99 of the 101 patients in that way.
Now think about that for a minute. We define an illness by a bunch of symptoms. Now, Ill say Dr. Peterson is a really fine doctor, and Im quite certain that hes not misdiagnosing Chronic Fatigue Syndrome. Hes really splendid. So, it could be that he has a really clean, tight population of folks in his freezer. But I would say, I think Im pretty damn good, and I think if I pulled out stuff from my freezer, there might be a couple of MSs in there or something else that evolved down the line. I mean, Im not sure. But its pretty impressive that out of 101 CFS defined by clinical case definition or a research case definition that they found 99 with virus. And if this is the case, thats pretty exciting. Its pretty impressive. And, oh, by the way, we have a biomarker. Not a small deal. A biomarker the virus itself. No better biomarker than something thats clearly, tightly associated with an illness.
