[Again, cross-posted into bionet.virology and, since this seems to be
moving away from immunology, followups set into bionet.virology only]
In article <4hmc6i$dp4 at is.bbsrc.ac.uk>, Mike Whelan <whelan at bbsrc.ac.uk> wrote:
>>point. I guess it boils down to what we describe as a "latent"
>infection. One argument could be that these are actually just normal
>infections held in check by the immune system. Consequently, any
>manifestation of disease will be more severe (?)
The evidence that latent infections are 'normal infections held in check
by the immune system' is pretty weak, I think. (I include persistent
infections in the latent infection category - I differentiate them by
saying that a latent infection - as with HSV - has few if any proteins
expressed, while a persistent infection, as with EBV, does express a
limited spectrum of viral proteins.)
Note that in the herpes viruses, the latent and persistent infections are
clearly following a specific and ordered program which is distinct from
the 'normal' (actually much less common) clinical infection. That is, the
viruses are clearly expressing a set of genes (or in the case of HSV, not
expressing certain genes, perhaps) that maintains this state; and the
state is actively maintained - it isn't a case of the virus being forced
into it.
As far as a role for the immune system - on the one hand, in immune
compromised people, herpes latent and persistent infections can reactivate
and be severe problems. However, this doesn't mean that the *normal*
mechanism for reactivation is being followed here. In fact, herpes
simplex can reactivate in spite of a fairly impressive host immune
response: antibody titers can be very high, and although there might be
moderate suppression of some cellular parameters, this is not severe.
(People with recurrent cold sores are not at risk of, for example,
Pneumocysti carnii infection.) Moreover, this moderate immune suppression
may be an effect, rather than a cause, of the viral reactivation, as
herpes viruses (and many other viruses) can probably cause a mild immune
suppression.
There are probably two distinct events in a clinical reactivation. One
is the actual, true, reactivation of the virus from its reservoir. The
other is the expansion of this virus into a clinically relevant
syndrome. I'd expect that the two events are only weakly related, and
that the second is more likely to be immune-related than the first - but
even that, I think, is going to be influenced by much more than the
immune system.
One piece of information that's missing is the level of immune response
in the microenvironment of the reactivation, but that's very difficult to
measure in any meaningful way.
Ian
--
Ian York (iayork at panix.com) <http://www.panix.com/~iayork/>
"-but as he was a York, I am rather inclined to suppose him a
very respectable Man." -Jane Austen, The History of England
