THOUGHTS ON VIRULENCE:
Thanks to all of you who have contributed to the recent
discussions of virulence; this exchange of ideas is very refreshing
and useful, and especially so because it builds on a major
presentation at the national meetings. I remember listening to a
senior member of our society, back in the late 1960s, bemoaning the
fact that the annual meetings always seemed like the end of
something--research finally presented after so much labor, friends a
year older, etc.--and for that reason it made him sad to come to the
meetings. But it's clear that in this one case, at least, the
meetings were a beginning instead of an end.
As you might suspect, this virulence discussion has generated a
reasonable amount of talk on the dirt roads of cyberspace, too, so I
feel a little bit of an obligation to pass along these ideas from the
hinterlands.
Back in the 1970s, when there were several people in the lab
working on kinetoplastid flagellates, and we had a large number of
species in culture, it became obvious that in order to talk to one
another about the work we were doing we had to distinguish between
"infectivity" and "virulence." "Infectivity" became the ability to
establish an infection; "virulence" became a measure of the speed with
which an infection progressed through its so-called natural course;
and, both were relative (but virulence moreso). That pathology
accompanied relatively high virulence was a given, although the
haemoflagellates were microparasites and it was thus impossible to
separate pathology from parasite reproductive rates. But it was also
a given that one could manipulate virulence, e.g. by passing certain
strains of __L. donovani__ through hamsters or cell cultures without
intervening axenic culture at room temperature. Infectivity, however,
was a more stable trait, in that a species' scientific name was more
of a measure of its infectivity--which in fact was host specifity
viewed from the parasite's perspective--than of its virulence.
Since that time, we have been involved with parasites that are
generally considered avirulent, i.e. non-pathogenic, but highly
infective--the eugregarines (which behave biologically as
macroparasites)--and that are rather extraordinarily diverse, mainly
because they appear to be quite host specific and their hosts are
extraordinarily diverse. For example, IF the beetle __Tenebrio
molitor__ is representative of coleopterans, with four species of
__Gregarina__, then there may be nearly a million species of the genus
__Gregarina__ in beetles alone. [We know that __Te. molitor__ is not
representative, however, so that the number of __Gregarina__ species
may be closer to 100,000, of which only 1% have been described.
{Clopton believes the number of undescribed __Gregarina__ spp. is
higher, possibly much higher, than 100,000}] When one considers the
rest of the eugregarines, one finds an equally remarkable diversity of
parasites, again with little evidence for virulence (pathogenesis).
By any commonly accepted definition of the term "success," these
eugregarine parasites are very successful. It remains to be seen
whether colonization of a new host, by a gregarine, involves initial
pathology followed by mutual resolution of the physiological conflict
to the standoff status--a traditional expectation. But the lack of
reproduction in the life cycle stage of interest (re the virulence
discussion), thus the macroparasitic behavior, requires that such
theoretical pathology be separated from parasite multiplication. So
it seems we can distinguish between pathology arising primarily from
parasite proliferation in the host, and pathology arising from other
causes ("physiological [biochemical, immunological] conflict"), at
least in theory, and a microparasite might produce one type, or the
other, or both, but a macroparasite is "restricted" to the latter.
(The adult schistosomes might well be a case of macroparasites
producing propagules [eggs] that in turn behave, pathologically, as
microparasites.) We might expect, then, that the evolutionary events
leading to a particular host/parasite relationship are a function
first of the parasite life cycle events that produce, or do not
produce, parasite multiplication in the host, and second of the
physiological (biochemical, immunological, etc.) compatability of the
host and parasite.
Parasite multiplication in the host, or lack thereof, in
virtually every case is a truly ancient and plesiomorphic character.
Thus the proliferation of parasitic nematode species post-dates the
evolutionary events that preclude production of new adult nematodes
from invaders all within (and only within) the body of an individual
host. Conversely, the proliferation of coccidian species post-dates
the evolutionary events that require production of new merozoites from
invaders all within, and only within, the body of an individual host.
If pathology associated with virulence is a driving force in the
evolution of parasitic life cycles, then evidence for such should be
found within microparasites only, and a proper comparative study of
these types of life cycles should produce some testable hypotheses.
If pathology is a byproduct of virulence, however, then the only thing
a parasite must accomplish is transition to the next life cycle stage
prior to the host's death. In this latter case, we might expect the
transition time to be rather fixed, especially in the case of large,
long lived, hosts.
Again, the very diverse coccidians might provide some interesting
clues to the relationship between pathology, virulence, and life
cycles. For example, we might ask: What is the range, among all
coccidians, in time and number of merozoite generations from
infection to oocyst production? If the range is small, and the time
short, compared to the life expectancy of an infected host, then one
must question whether virulence related pathology is (has been) a
significant driving force in the evolution of the H/P relationships in
this system. Conversely, when comparative study of a particular
system reveals a wide range of transition times, and life expectancies
of infected hosts close to at least some of those times, then the
hypothesis of virulence/pathology driven co-evolution seems plausible.
A traditional view of virulence--life cycle--evolution interactions
predicts one would find old H-P associations in which the parasite
underwent many asexual generations, produced large numbers of oocysts,
and generated little or no pathology (accomodation joined with
production of large numbers of propagules). IF indeed we define
success in terms of numbers, then evolutionary co-accomodation in
coccidia should produce an inverse relationship between extent of
pathology and numbers of parasite generations among a group of related
host species (some of which were colonized recently). However, my
cursory examination of the literature suggests exactly the opposite is
the case (pathology and number of asexual generations are directly
related). Is it conceivable that co-accomodation results in REDUCED
virulence, in this case reduced oocyst production, i.e. reduced
"success?" If so, then perhaps we parasitologists might define
success as persistence of a species, rather than as the production of
large numbers of offspring (not a new idea).
The other aspect of virulence that I've not seen discussed at
length in the parasitological literature is the relative contribution
of parasitism to a host species' fitness in nature. Granted, much of
the parasitological literature addresses problems of disease, with the
tacit assertion that disease reduces fitness. And, granted, that
there are some elegant studies demonstrating (at best), or suggesting
(at least) a relationship between parasitism and mating success, and
even mate choice. However, there is not to be found a broad and
comparative examination of the relative contribution of parasitism to
overall fitness. If one could determine, for example, all of the risk
factors for an American Robin egg from the time it's laid until its
chick reaches adulthood and produces another egg, then list those risk
factors in order of their impact, where would the nearly hundred
parasite species reported from __Turdus migratorius__ be placed? And
would they be lumped together, or ranked individually?
It seems to me that we need some models that take into account
the ideas of plesiomorphic vs. apomorphic characters, applying those
ideas to aspects of parasite biology that may not yet have been
studied in such a way (transit time, numbers of asexual generations,
nature of biochemical interaction between host and parasite, etc.),
combined with host species' life expectancies and relative risk
factors in nature. The data sets to be examined might include ones
necessary to answer the question: Do the life cycle features we feel
intuitively should be variable actually vary among a group of related
parasite species?
John Janovy, Jr.
Biol Sci; UN-L
Lincoln, NE 68588-0118
jjanovy at unLinfo.unL.edu
