Viruses most often enter the
host through respiratory, gut or genital mucosal surfaces,
although they also may directly enter the blood stream
via hypodermic syringe, animal bite or insect bite. Entry
through the blood is likely to shunt the virus directly
into the spleen, where T cells, B cells and antigen-presenting
cells (APC) are readily available to initiate an immune
response. In the more common peripheral routes the viruses
will likely encounter dendritic cells that coat the various
mucosa, which then carry them into the circulation and
home to peripheral tissue like lymph nodes, where they
trigger the immune response involving B and T lymphocytes.
The survival of viruses
depends on the survival of susceptible hosts.
In fact, there is no evolutionary advantage
for the pathogen to cause the end of its host
too rapidly. Therefore, the vertebrate and
viruses have co-evolved complementary facets
to maintain a delicate balance between life
and death. A virus should not be overtly cytolytic
and must regulate its lytic potential. This
type of virus will be able to persist into
the host because it does not kill the host
cell too rapidly or produce excessive damage.
Furthermore, viruses try to avoid detection
and elimination by the host immune system.
Therefore, the outcome of many viral infections
is immune containment rather than complete
eradication of infection. The consequence of
this immune containment is the development
of persistent viral infections that last as
long as the host lives.
Persistent viral infections
have traditionally been divided into two categories:
chronic infection and latent infection. There
are cases of chronic viral infections (viruses
are actively replicating), like the hepatitis
B virus, that are maintained under control.
This can be achieved, at least in part, through
the development of cytotoxic T lymphocytes
(CTL), which have the capacity to lyse and
kill infected cells before the production of
progeny virions. Latent infection is usually
asymptomatic, as opposed to chronic infection
that is symptomatic, and takes place when the
viral genome persists in integrated or episomal
form. In this case, infectious particles are
generally not produced except during intermittent
episodes of reactivation, as for Herpes virus.
This distinction between chronic and latent
is not mutually exclusive. For example, HIV-1
infects the non-dividing cells like monocytes/macrophages
and dendritic cells or the dividing cells like
CD4+ T lymphocytes. In this case, the infection
can either be chronic, due to constant viral
production by infected T lymphocytes, or latent
because HIV-1 genome is integrated into the
host chromosome and is waiting to be activated.
It is very common to encounter
viruses that tend to fight the host defense
mechanisms to facilitate their own survival
for spreading the infection. Viruses have come
up with many ways to escape recognition and
elimination by host antibodies and T cell response.
Some viruses have evolved molecules that override
apoptotic programs (cell death), prevent viral
recognition or immune cell activation to promote
infected-cell survival until virus assembly
is complete, persistence is established or
cellular transformation occurs. Apparently,
the HIV-1 has developed several mechanisms
to escape the immune system, such as by direct
or indirect killing of immune cells. HIV-1
has also found the way to escape to the CTL
response (specialized T lymphocytes that kill
infected cells) or antiretroviral drug treatments
by the usage of high rate mutations into viral
proteins. Mymetics has discovered that, in
addition to the different immune escape strategies
used by HIV-1, the gp41 viral transmembrane
glycoprotein of HIV-1, as well as transmembrane
glycoprotein from other retroviruses (FIV,
SIV, HTLV-1), have evolved to mimic the interleukine-2
(IL-2) from their infected host. Consequently,
an immune response toward the gp41 might also
potentially cross-react with the host IL-2,
which may lead to severe defects in the IL-2
cytokine pathway and contribute seriously to
impair the cytokine network from the immune
system, thus weakening the host's defense. |
