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 Why
do viruses cause disease? As intracellular parasites they grow
at the expense of the host, yet many infections are
non-virulent. We tend to focus on unusual outcomes of
infection that are important to the individual but trivial for
host–parasite evolution, for example, paralytic polio or viral
cancer. The assumption that the features of disease help
onward transmission of the virus is true for, say, rabies, but
not for AIDS or neurodegenerative diseases. Moreover, minor
host differences can result in major changes in pathogen
virulence. Although viral burden relates to disease severity,
pathogenesis is not necessarily coupled with transmission
dynamics.
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Most of the articles in
this issue are devoted to molecular pathogenesis and the host
response to virus infections, in other words, how viruses
cause damage to their hosts. I wish to debate why they cause
damage, and to challenge the notion that virulence is usually
the result of natural selection acting on transmission. Of
course, these concepts are not special to virus infections;
they are equally pertinent to other infectious microorganisms
and parasites, but I shall restrict my discussion to viruses
of vertebrates.
Virulence and pathogenesis are not quite the same thing. The
former is viewed from the point of view of the virus and
latter from its effect on the host
[1]. Evolutionary biologists like the term virulence;
molecular virologists would sooner mention pathogenesis, at
least when writing a grant application or an article for
TIM! Thus virulence and pathogenesis represent two sides
of one coin, but why do viruses cause damage? If the answer is
that they propagate at the expense of their host, why, then,
do many 'successful' viruses not cause disease? It is probably
no coincidence that two 'harmless' viruses of humans, TT virus
(TTV) and GB virus C (GBV-C), were only discovered in the
1990s. They were revealed by molecular cloning methods while
searching for non-A, -B and -C causes of hepatitis
[2,3] , but appear to be avirulent passengers.
Virulence and transmission dynamics
The old adage, repeated in many medical textbooks, is that
'well-adapted' parasites are relatively harmless to their
hosts. Although long-equilibrated viruses have in many cases
become attenuated, a general assumption of evolution towards
avirulence is not valid because the probability of onward
transmission could be dependent on factors related to
virulence, such as viral load. For example, the live,
attenuated Sabin vaccine strains of poliovirus tend to revert
towards neurovirulence during passage through infants, such
that non-immunized contacts can acquire virulent infection. In
the Americas, where wild-type virulent poliovirus has been
successfully eradicated, the few cases of paralytic polio that
occur each year are attributable to secondary or tertiary
transmission of virulent revertants of the vaccine strain.
This has led to arguments for switching to immunization with
killed Salk vaccine, as still used in Scandinavian countries.
The impediment to its worldwide use is the need for
inoculation and booster doses.
Neo-Darwinian evolutionary biologists go further, and hold
that virulence is an outcome of successful adaptation. Ebert
and Hamilton
[4], for example, have argued that there is a trend
towards evolution of virulence in parasite–host relationships.
Ewald
[5] appears to think that all disease manifestations in
the host directly result from selective evolution of the
pathogen for efficient transmission, an over-simplistic view
in my opinion. Perhaps the most valuable commentary on
virulence and transmission dynamics is to be found in Anderson
and May
[6]. They estimate that virulence can indeed affect onward
transmission of a virus or parasitic organism with a formula
relating to its basic reproductive rate, R0:
where
is the disease-induced host mortality or morbidity rate,
is the transmission coefficient,
is the recovery rate, µ is the mortality rate for all causes,
and N is the total population size. If neither the
transmission rate nor the recovery rate depend on virulence,
then R0 is maximised by making
infinitesimal, that is, non-pathogenic.
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BioMedNet Magazine
17th - 30th July 2002 |
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