Date: Sun, 03 May 1998 12:35:54 -0400
From: "Eddie Bollenbach"
Subject: New Ideas of Polio Infection
I got my hands on a review of what we currently know about Polio from the Journal of Neurovirulence this week. It's interesting to note that we are increasing our understanding of the biology of Polio Virus, its mechanisms of infection, and its capability to persist inside the cells it infects, years after its threat in this hemisphere has passed. It is also ironic that polio virus is primarily a gut infector. The virus grows in the intestines of those infected and rarely goes anywhere else. It is in the gut that the virus reproduces and is impelled to exit the body. Both of these activities are critical to its survival and further evolution. The paralysis it causes, in less than 1% of those infected (you and I), has been worthless to it biologically (It cannot exit the body from the Central Nervous System), and has been the initiator of its demise because of the scientific resources successfully organized toward it's destruction.
I also learned some new things about the virus. One mystery concerns how it moves to the Central Nervous System (Brain and Spinal Cord) from the gut, in those who develop paralysis. The two contenders are:
- 1. Through the blood via a viremia (blood infection)--apparently certain white blood cells have Polio Virus Receptors on their surfaces and can shuttle this extremely tiny virus around. Or----------
- 2. By migration through the cells of the nervous system, ultimately arriving in the CNS. I never knew that the Thoracic Spine escapes the ravages of damage that the virus wreaks in the cervical spine, lumbar spine, and lower parts of the brain. The Thoracic Spine escapes unmolested. This is so because the pathways to it are probably missing (this is evidence for the nerve transport idea, since blood and capillaries obviously nurture this area as other spinal areas).
Until very few years ago polio was thought to kill every cell it infected. In the parlance of virology we would say it was characterized by a lytic infection (it bursts the cells it infects releasing hordes of new viral particles in about 8 hours after penetration of the virus into the cell). But if you think about it this doesn't make a whole lot of sense. Because a lot of neurons survive, and we have been hearing that "If you had polio all the neurons in your body have been infected". If that is so then polio must not be exclusively a lytic infection. Right? Well, what else is there? A persistent infection! Surely there is a co-evolution occurring when the nervous system, with its billions of cells, is infected by polio. The most susceptible cells die outright, some undergo changes but manage to survive. Sometimes you can see an infected cell change e.g. it becomes rounder and visible bodies appear inside the cell. This is called the "cytopathic effect" and it occurs commonly during many viral infections. Many of these cells survive. But where did the infecting virus and its offspring go? When you think of the number of polio viruses that can be produced (because they are very small) such a cell could live but shed 100 million or more virus particles. These are actually counted in cell culture (where polio virus is grown inside cells that are in petri dishes in the lab). We can grow human and other cell types that can be infected by polio in the lab outside the body. And we can now maintain persistent infections where the cells do not die. However, these cells are not mature human neurons but rather embryonic cells e.g. neuroblastoma cells. And, interestingly, the mutations of polio virus that allow it to persist seem to affect the same genes in almost all cases: genes that code for the manufacture of part of the protein case that enshrouds the virus. Like Humpty Dumpty it can't put itself back together again but can survive inside the cell.
Analogous to Murdoch's Law (I think) which states that computer technology doubles its capacity every 18 months, we have a corollary in molecular biology. That's how fast our abilities to investigate at these tiny viral and molecular levels are accelerating now. For example, we have engineered transgenic mice (mice, by the way, always could be infected with polio if injected with the virus), but now can serve as a model of human infection. The genes for the Human Polio Virus Receptor have been added to its nuclear repertoire and the receptor will now take in polio virus from the gut and into the spinal cord and brain. Then, after infection, the mice can be sacrificed and the spinal cord studied. What has been found is that the virus does indeed persist in the spines of the mice that survived a paralytic infection.
We also know that in the spinal cords of those of us with PPS are fragments of polio virus. These fragments are not present in the spines of those who have had paralytic polio but no PPS. We also know that an antibody against polio virus is present in PPS patients and not in old polio survivors without PPS. The nature of the antibody is telling too. It belongs to a class of antibodies called IgM (Immunoglobulin M) which appears _early_ in an infection. Other antibody classes appear later in an infection.
Does this correlation mean anything in terms of PPS? If so, can the process be arrested as we learn more? I don't think it exorbitant expectation to believe that soon chemicals like the HIV protease inhibitors will be easily produced to interfere with polio virus's neuronal activities.
I was surprised to see the degree of research into the life cycle of PV that is now occurring. I think this review can only stimulate more interest. Half the paper contained a bibliography of research into the biology of polio virus back to the 50's. The next few years should be interesting ones to those of us interested in this.
The Reference is: JOURNAL OF NEUROVIROLOGY (1998) 4, 1-26
MOLECULAR ASPECTS OF POLIOVIRUS BIOLOGY WITH A SPECIAL FOCUS ON THE INTERACTIONS WITH NERVE CELLS, Bruno Blondel, Gillian Duncan, Therese Couderc, Francis Delpeyroux, Nicole Pavio and Florence Colbere-Garapin Pasteur Institute in Paris
Contact Professor Edward P. Bollenbach