The Virus way to Influence Cell Fate, Survive and Persist
Abstract
In order to thwart a viral infection, the host has developed an
integrated defense network that includes innate and adaptive immunity as
well as regulated cell death (RCD), which appears to represent an
ancestral defence mechanism for the host. Indeed, RCD is important to
control several aspects of the cell fate in various situations, from
embryonic development and adult tissue homoeostasis development, to
stress response, including viral infection, where different but
complementary highly regulated arms of the complex RCD process exist
and can be activated, with various consequences. In order for a host to
cope with a viral infection, RCD can play a critical role in the elimination
of virus-infected cells and/or to control the cell-to-cell viral dissemination
to protect the whole organism. During the pathogen-host co-evolution,
viruses have developed various strategies to counteract defenses of the
host and, among other things, they have acquired the capacity to subvert
host-cell RCD. For some viruses, disabling host-cell RCD, at least for
some time, could represent an important step in the replication cycle as an
effort to prolong their own survival and possibly establish a persistent
infection, which can lead to chronic diseases. On the other hand, other
viruses may take advantage of RCD to facilitate shedding and
disseminate more efficiently in the host or to prevent the presentation of
viral antigens to the immune cells. By encoding numerous proteins that
either are homologs to cellular apoptosis-regulatory factors or interfere
with cellular proteins that control RCD-related pathways, several
different viruses are able to induce or modulate the different cellular
pathways that control RCD. Virus modulation of cell death participates in
the pathological process associated with several human diseases;
therefore understanding mechanisms and consequences of virus
interactions with the host cell-death machinery is essential to understand
potentially pathologically relevant consequences that will help in the
design of intervention strategies and the development of antiviral
therapies.