Ebola Tissue Tropism and Pathogenesis
The Filoviridae Journey:
After transmission to a new host, the virus enters a cell through a mechanism
that has yet to be determined. Once inside the host cell's cytoplasm, the filovirus
uncoats itself and releases transcriptase, which is contained in the virion. Transcriptase
transcribes the viral -ssRNA into the complimentary +ssRNA. This positive, single
stranded RNA will then be used as the template for the new viral genomes. Soon
after the infection, the cell develops cytoplasmic inclusion bodies that contain
the highly structured viral nucleocapsid (the nucleocapsid contains the genome
and can sometimes have other proteins in it as well). After the nucleocapsid has
been formed, the new virus will self-assemble and bud from the cell membrane stealing
some of the membrane for its envelope.
Not very much is known about the pathogenesis of filoviruses. But we do
know that Ebola attacks cells important to the function of lymphatic tissues.
It can be found in fibroblastic reticular cells (FRC) among the loose connective
tissue under the skin and in the FRC conduit (FRCC) in lymph nodes. This
allows the virus to rapidly enter the blood and leads to disruption of lymphocyte
homing at high endothelial venules (HEV). For more information about the
relationship of ebola pathogenesis to lymphocyte homing in lymph nodes,
please see Role of the
FRCC in Lymphocyte Homing.
Ebola virus seems to be most active in infecting fibroblasts of any type (especially
fibroblastic reticular cells). The next most frequent cell types are mononuclear
phagocytes with dendritic cells more affected than monocytes or macrophages. Endothelial
cells become infected after the the connective tissue surrounding them is fully
involved. Then, almost as a final insult, epithelial cells of any type are infected.
In general, epithelial cells become infected only if they contact other cells
that amplify the virus such as fibroblastic reticular cells (FRC) and mononuclear
cells. This would be true for skin appendages like hair follicles and sweat glands
because they are heavily vascularized and have a lot of FRC networks associated
with them. Liver cells and adrenal gland epithelial cells have fibroblastic reticulum
as their main connective tissue and both have resident mononuclear cell phagocytes
hanging on FRC cells near the blood/epithelial cell interface.
The time sequence of infection and spread of ebola is difficult to speculate on
because most studies have been conducted on "autopsied" animals, i.e. they are
at the end stage of infection.
While some regions of the body or organ systems may be at earlier stages of infection at the time of death it is not a good idea to use this information to derive a theory on sequence of infection and spread. Only through analytical experiments in vivo where sequential necropsies are performed on animals euthanized according to a time course protocol can the actual sequence of infection and dissemination be characterized.
Electron micrographs and immunohistochemistry images
of the pathogenesis of Ebola Zaire
©1999 Tara Waterman
