Rabies, a virus, but oh what a virus

Rabies, a virus, but oh what a virus

The specific ways that rabies affects the nervous system, its sole target, can tell us volumes about human behavior, normal and abnormal, and human development, from infant to the fully socialized, highly civilized beings we are expected to become as adults.  It can show us the extent to which humans act as vampires and werewolves, and the meaning of such behavior.  Yet, the rabies virus has not given up its knowledge, although it has been part of our written history since writing began. 

So what is this rabies, this lyssavirus that I am rabid to understand?  Briefly, it is a virus, meaning it contains a long string of RNA (ribonucleic acid) molecules whose.  The specific order of these different RNS molecule makes a code on how to make various proteins. The RNA is packaged inside a protective shell that also contains a specific chemical motif that will provide attachment to the cell it will infect.  Viruses do not have the machinery to gather the necessary material – amino acids – nor the assembly lines to actually construct proteins or RNA.  Therefore, replication of viruses is dependent on the virus’s ability to enter and take over the machinery of a cell that is self-replicating.  Entry must be made into a host cell, that is, a cell whose protein-making capabilities can be manipulated by the viral RNA.  This entry primarily occurs via attachment of the virus to a receptor molecule on the outside surface of the host cell.  Once anchored to the outside of a host cell, the virus may have its own machinery for injecting its RNA through the cell’s membrane (its ‘skin’).  More often, the receptor is internalized into the host cell as part of the normal replacement of that receptor.  In this case, the virus just hitches a ride into the cell.  Lyssavirus uses this method, hitchhiking, to enter its host cells.

The receptors used by many viruses are fairly common across many types of cells or the cells having the necessary receptor are fairly frequent.  The rabies virus is unique in the level of specificity of its target.  Rabies can only infect (enter and take over) neurons.  And, it can only infect neurons of the brain and spinal cord, that is, the central nervous system (CNS).  Neurons wholly outside of the CNS, in the peripheral or autonomic nervous systems or sensory neurons, apparently do not have the appropriate receptor molecule.  Nor does any other cell in our body!  Among other things this means that just because one is bitten by a rabid animal, even having virus-laden saliva in the bloodstream, does not mean that one is infected.  At this stage the victim is simply exposed.  While this is true of any virus, for most viruses the time from exposure to infection is very short.

The CNS is well-protected from many kinds of unwanted material, be it bacteria, toxins, even the body’s own immune cells.  This is a result of the blood-brain barrier.  This consists of very tight junctions – very tiny spaces -- between cells of the blood vessels in the CNS.  The CNS maintains a stringent regulation over what is allowed to enter, or leave, the CNS.  Rabies viral particles are too large to slip between the cells of the cerebral blood vessels.  The virus also cannot infect the cells of the blood vessel walls and thus cannot enter the CNS in that way. 

There are a few CNS neurons that extend out of the CNS.  One type is the neuron that controls skeletal muscle movement, called skeletal motorneurons.  Almost without exception it is the endings, nerve terminals, of these CNS neurons, which are located in our skeletal muscles that are the target for rabies infection.