Mechanisms of Chronic Infections

[biologics at worldnet.att.net]

Simon Fox wrote:
> 

> [stuff deleted]
> Since cell-mediated immunity is the hosts most effective mechanism
> for the elimination of viral infections the capability of a virus to
> persist implies viral mechanisms for circumventing this defense.
> Most instances described involve interference by viral proteins in
> the processes of antigen processing and presentation. This can
> potentially occur at any of the stage(s) involved. Alternatively the
> viral products may act directly against the immune system and its
> cellular components. Furthermore there may be other more subtle
> mechanisms involved.

Another possibility is the population dynamics of the virus in a given
host environment.  If you take an analogy from ecology, there are lots
of instances where ectoparasites, insect pests, plant pathogens etc.
persist in a given environment despite predation and various host
mechanisms of defense.  In most cases, there is no adaptation or
"escape" due to some advantageous mutation.  Instead, the birth and
death processes of the pest/parasite/virus coupled with the
birth/death processes of the host can determine persistence of the
former. Often, a simple time-lag effect is all that is required - if a
virus begins replicating before the immune system can detect it, and
the replication rate is high enough, there is the possibility that at
least some successfully infectious virions will be produced.  If, on
average, one successfully infectious virion per infected cell is
produced in the succeeding generation, then persistence is guaranteed.

In HIV, there are a number of mathematical models that can account for
persistence without requiring that we postulate the existence of
escape mutants, or viral interference, e.g., Perelson et al. (1993),
Schenzle (1993), Bremermann (1995).  All these models explain
persistence on the basis of the dynamics of the viral and host-cell
populations.

- Allen Rodrigo
Department of Microbiology,
University of Washington