Mechanisms of Chronic Infections

[Simon Fox]

Hi,
I am seeking information, suggestions and even debate regarding
mechanisms by which viruses maintain persistent/chronic infections in
spite of the best efforts of their implacable opponent: the hosts
immune system. In all liklehood a substantial proportion of such
infections are benign with few or no clinical manifestations. However
in a small subset there are serious consequences for the host.
Probably the most intensively studied is HIV (which has certainly had
a lot of money thrown at it!). In all but a few, the mechanisms of
viral persistence are poorly understood.

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.

In our laboratory we are investigating the genetics of Hepatitis C
virus (HCV) with relation to its genotypes and dynamic behaviour of
quasispecies during chronic infection and in response to therapy. One
of the significant features of this virus is the high percentage of
non-resolving infections which progress to chronic disease. A
postulated mechanism for this persistence is the error prone
replication and consequent genetic variability of the virus giving
rise to escape mutants. Although we are investigating this mechanism,
we feel it is unlikely, given the frequency of chronic HCV, to be the
only strategy used by this virus.

I am interested in mechanisms from other viruses which may be worth
investigating in HCV. Obviously a search of the literature (unlike
many newsgroup posters' I did bother to do this first) has turned up a
few. Any suggestions or comments would be most welcome.

Bye