Let's discuss first the pathogenesis
of the vector-borne viruses.
Most of these have an animal or
enzootic cycle without human infection.
In other words, they cause disease in
animals that never gets to humans.
For example, the equine encephalitidis.
They are spread by the bite of a mosquito or a tick
and the virus is able to replicate
in dendritic cells and macrophages
in the local tissue near the bite,
spreads to the lymph nodes,
and from the lymph nodes gains access
to the bloodstream causing viremia
and spread to the central nervous system.
And there are multiple
host and viral factors involved.
First of all, there is infection of
endothelial cells, blood vessel cells.
The ability to penetrate the micro vasculature
and penetrate the choroid plexus in the brain
and then when they get into the brain
they cause infection and death of neurons either directly
or by apoptosis,
which is an important mechanism
of nerve cell destruction.
Rabies, on the other hand,
is common in developing countries in dogs,
but pretty rare in developed countries.
there have been no cases from
dog bites in the United States
or Puerto Rico in the last four years from dog bites.
And in developed countries,
93% of rabies is from raccoons,
and most importantly, from bats.
Skunks and foxes also can carry these.
And the bottom line is,
these animals are normally afraid of human beings.
So, for example,
if a raccoon walks into your yard
and doesn't seem to be afraid of you,
that raccoon may well be rabid.
Ditto a fox.
And in rabies, the bite from the infected
animal is teeming with saliva viruses.
And the saliva invades the motor and
sensory nerves at the site of the bite
and the incubation period can be short, say, seven days
or six years or longer.
And what happens is that the virus
moves to the dorsal root ganglia
and the spinal cord
and then causes neuropathic pain
and then moves up the spinal
cord to cause encephalitis.
And the closer the bite is to the brain,
for example, a bite on the face,
the more rapid is the incubation period.
With respect to the pathogenesis
of the herpes simplex virus,
there are lots of questions that remain.
The exact mechanism of central nervous
system invasion is not really known.
It could be that the herpes simplex virus
causes this classic gingivostomatitis
and could cause inflammation
of the oral mucosa and the gums
and go through the axons
to the trigeminal ganglion and then
into the central nervous system.
it could invade the olfactory bulb
through the nasal mucosa,
go to the frontal and medial temporal lobe.
But the cause of cell death and tissue injury
is either from direct neuronal killing
or from, as in the other viruses, apoptosis.