The Parasitic Wasp's Secret Weapon
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The Parasitic Wasp’s
Secret Weapon
Parasitic wasps must develop inside living caterpillars.
They survive this hostile environment by smuggling
in a virus that suppresses their host’s immune system
by Nancy E. Beckage
T his caterpillar will never be-
come a moth. It lurks deep in
the foliage of a tasty tomato
plant, hidden from predators, but its
enemy has found it anyway. In search
will die as well. Yet the caterpillar can-
not be allowed to gain the upper hand
using its immune defenses. Much of the
responsibility for maintaining this deli-
cate balance falls to the wasp’s viral ac-
of a nanny for her offspring, the para- complice. Like the wasp, many parasites
sitic wasp has homed in on the distinc- of insect hosts have evolved associa-
tive scent of her lepidopteran victim tions with bacteria and viruses that help
and its lunch. Now the tiny wasp in- them perform their often deadly deeds.
jects a clutch of eggs through the cater- the University of
pillar’s tough cuticle and into its body Microbial Weapons Cambridge sus-
cavity, where her larvae will thrive by pected that female
feeding on their living nursery. At a crit-
ical moment in development, the wasp
larvae will burst through the flanks of
A simple example of such a partner-
ship occurs in certain parasitic
worms that carry a virulent bacterium
Venturia wasps in-
ject substances re-
quired for successful
the caterpillar to spin their cocoons on in their digestive tracts. These worms development of their
its surface. These wasps eventually de- regurgitate the bacteria into their insect progeny into host larvae
part as adults, metamorphosis com- hosts, killing the hosts within days of along with eggs during
plete, but their host is now destined to infection. The rapidly dividing bacteria the process called oviposi-
die as a caterpillar. are an immediate food source for the tion. In particular, Salt noted
If this were a one-on-one interspecies developing worms, and they provide that the ovary of the female
scuffle, the caterpillar might stand a further sustenance by secreting diges- wasp harbors substances that
chance—it has an immune system capa- tive enzymes that soon turn the host ca- prevent destruction of wasp eggs
ble of engulfing and killing invading daver into a nutrient-rich soup. In re- by the caterpillar’s immune cells.
wasp eggs before they can do permanent turn, the bacteria benefit by using the Normally, injected wasp eggs float
harm. The wasp, however, does not worms as vehicles for invasion of new freely in the bloodlike fluid, called the
come to this encounter alone. In addi- hosts. These interacting partners are hemolymph, that fills the body cavity of
tion to her eggs, she injects hordes of strictly independent organisms—they the caterpillar. When Salt washed the
virus particles. These viral warriors ra- do not share genes. wasp eggs prior to injection, however,
pidly defeat the caterpillar’s immune re- In contrast, the interaction between they provoked a rapid immune response.
sponse, tipping the balance of power in endoparasitic wasps and the virus they These eggs, stripped of an unidentified
favor of the wasp progeny. The cater- exploit is more intimate. Not only are factor, were quickly attacked by the
pillar, doubly parasitized, slowly ceases the fates of the partners intertwined, but host’s immune cells and ultimately killed.
feeding, fails to pupate and dies a pre- their genetic material is also permanent- In 1973 electron micrographs taken by
mature death. ly mingled. And the relationship goes
Host-parasite relationships such as further—the wasp and the virus possess
those involving the wasp, the virus and related genes. All this raises a thought-
WASP AND CATERPILLAR are the Da-
the doomed caterpillar are among the provoking question: Are the wasp and vid and Goliath of the insect world. The
most complex in nature. The wasp is an the virus two entities or one? huge caterpillar’s immune system threat-
endoparasite—it must develop inside its The first hint that endoparasitic wasps ens the wasp’s eggs, which must mature
host. If the caterpillar dies before the might have unusual weapons in their inside a living host. But the tiny wasp pre-
wasp larvae are properly fed, the wasps arsenal came in 1965. George Salt of vails using a deadly weapon: a virus.
82 Scientific American November 1997 Copyright 1997 Scientific American, Inc. The Parasitic Wasp’s Secret Weapon
ROBERTO OSTI Copyright 1997 Scientific American, Inc.
WASP LAYS WASP LARVAE PREVAIL
EGGS IN
CATERPILLAR
LAUREL ROGERS; STEVEN H. HARWOOD (top and bottom micrographs); MARK D. LAVINE (center micrograph)
EGG IS ACCOMPANIED BY
a OVARIAN FLUID AND VIRUS
EGGS ARE CATERPILLAR’S IMMUNE SYSTEM
WASHED FIGHTS OFF INVASION
EGGS WITHOUT
OVARIAN FLUID (AND VIRUS)
b ARE INJECTED INTO CATERPILLAR
WASP LARVAE PREVAIL
WASHED EGGS
ARE INJECTED INTO
c CATERPILLAR WITH VIRUS
BATTLE OF THE INSECTS rages between the caterpillar and not so fortunate. In the laboratory, however, wasp eggs that have
the wasp. Wasp eggs escape attack by the caterpillar’s immune been washed lack the protective virus (b) and are rapidly en-
system thanks to a virus injected into the caterpillar by the wasp gulfed by the caterpillar’s immune cells (center micrograph); no
along with her eggs (a). The virus disables the caterpillar’s im- wasps survive this encounter. Injecting pure virus along with the
mune cells, allowing the free-floating eggs (top micrograph) to washed eggs (c) allows the wasp eggs (bottom micrograph) to
develop into normal wasp larvae. The fate of the caterpillar is develop into larvae and emerge from the caterpillar.
Susan Rotheram, also at Cambridge, purified virus. But how exactly do the wasps: certain cells, known as hemo-
offered a clue to the identity of the pro- viruses—today called polydnaviruses cytes, circulating in the caterpillar’s blood
tective substance. These images showed (pronounced “puh-LID-nah-viruses”)— undergo rapid physical transformation.
that the surface of a Venturia egg be- disable the caterpillar immune system? Graduate student Mark D. Lavine has
comes impregnated with viruslike parti- seen these effects within a few hours of
cles as it passes through the wasp’s ovi- Immune Deficiency oviposition. Affected hemocytes “round
duct during oviposition. up,” failing to adhere to substrates such
Nearly a decade later Donald B.
Stoltz of Dalhousie University conduct-
ed an extensive taxonomic survey of
T o answer this question, my col-
leagues and I study the parasitic
wasp Cotesia congregata, which can
as glass or parasite eggs. They also un-
dergo extensive blebbing, or pinching
off of bits of their membrane and cell
parasitic wasps in collaboration with lay hundreds of eggs in each caterpillar. contents. The damaged hemocytes
S. Bradleigh Vinson of Texas A&M These eggs hatch into larvae that dine clump together and are removed from
University. They showed that viruslike on the host’s hemolymph fluid instead circulation. Overall, this transforma-
particles are invariably found in certain of consuming its tissue, thereby allow- tion bears a striking resemblance to the
wasp species that develop as internal ing the infected caterpillar to survive cell suicide, or apoptosis, that occurs in
parasites of lepidopteran hosts. More- well past emergence of the wasp proge- mammalian cells [see “Cell Suicide in
over, they observed that these viruses ny. Manduca sexta, the tobacco horn- Health and Disease,” by Richard C.
replicate exclusively in the ovarian tis- worm, serves as our model host. Any- Duke, David M. Ojcius and John Ding-
sue of female wasps. During oviposi- one who grows tomatoes has probably E Young; Scientific American, De-
tion, the wasp injects thousands of viri- had a run-in with these giant leaf-green cember 1996].
ons into the caterpillar along with one caterpillars, which forage on tomato, Granulocytes and plasmatocytes are
or more eggs. tobacco and jimsonweed and often among the caterpillar hemocytes most
It seemed reasonable to suspect that grow to the size of a man’s little finger. affected by parasitism; Michael R.
these viruses are the ovary-derived sub- Tobacco hornworms are convenient to Strand of the University of Wisconsin
stances that accompany wasp eggs into work with in the laboratory: obtaining has shown that granulocytes in particu-
the host and squelch the host’s immune blood samples from these enormous cat- lar die by apoptosis. These are exactly
response. The evidence was purely cir- erpillars is easier than obtaining samples the host immune cells that respond to
cumstantial until 1981, when Stolz, Vin- from mice. foreign objects, including Cotesia eggs.
son and their co-workers finally con- We have observed one immediate con- In a normal immune response, granulo-
firmed that this job can be performed by sequence of the parasitism by Cotesia cytes first release granules that coat the
84 Scientific American November 1997 Copyright 1997 Scientific American, Inc. The Parasitic Wasp’s Secret Weaponinvading egg. Plasmatocytes then ad- protein inside hemocytes one day after hemocytes. Webb has shown that imme-
here to the egg surface in multiple lay- oviposition, when these cells were quite diate but short-term protection against
ers, forming a thick capsule that even- disabled. We continued to find evidence immune cells is conferred by ovarian
tually kills the egg inside. Selective re- of EP1 in the caterpillar for six days; protein molecules injected directly into
moval of the granulocytes and the hemocyte function returned to normal the host by the wasp. The job of long-
plasmatocytes from circulation disables on the eighth day—but too late for the term protection then falls to the polyd-
the caterpillar’s first line of defense caterpillar to kill the wasp larvae. navirus through sustained viral protein
against the endoparasite. Similar phe- Researchers led by Otto Schmidt of production in caterpillar cells.
nomena occur during human immuno- the University of Adelaide have found a
deficiency virus (HIV) infection in hu- similar correlation in a different host- Arresting Development
mans. In that case, the virus targets parasite pair: hemocytes first become
lymphocytes, causing the clumping and
apoptotic death of the cells. Opportu-
nistic infectious agents are then free to
damaged during the brief period when
viral protein is produced—then immune
response rallies in two or three days. We
A nother important aspect of the Co-
tesia-Manduca-polydnavirus tri-
partite relationship (and the one that
ravage the victim, much like the wasp speculate that hemocyte damage occurs first piqued my interest in the field) is
progeny that overtake their unfortunate as long as such viral proteins persist; the way the parasite manipulates the
caterpillar host. once viral protein levels drop, damaged development of the host. A growing in-
When we inject unparasitized tobacco hemocytes would recover or be replaced, ternal parasite benefits by extending the
hornworm larvae with purified polyd- replenishing the functional supply. interval over which its host remains a
navirus, caterpillar hemocytes undergo One consequence of this timing is feeding larva. For this reason, many en-
changes in appearance and behavior that the host immune response resumes doparasites develop strategies to delay
analogous to those we observe in nor- in full force before developing wasps are host metamorphosis. I was particularly
mal parasitism. But if we chemically in- ready to leave the caterpillar. Unlike vul- interested by the case of the tobacco
activate the virus prior to injection, the nerable eggs or young larvae, however, hornworm parasitized by Cotesia, be-
hemocytes remain unaltered. This re- older wasp larvae seem able to with- cause this host remains developmental-
sult suggests that virus capable of di- stand active immune cells on their own. ly stunted long after the wasp progeny
recting manufacture of viral proteins is Polydnavirus provides a long but tem- leave the body cavity; the caterpillars
required for immune suppression. porary reprieve from immune attack, often linger two weeks before dying.
Graduate student Steven H. Harwood allowing the wasps to become mature Developmental arrest in lepidopteran
has shown that polydnaviral proteins enough to protect themselves. hosts is mediated through the endocrine
do indeed appear rapidly in the cater- Bruce A. Webb of the University of system. I studied endocrine disruption
pillar host. We detect the first evidence Kentucky, who works with parasitized caused by parasitism as a graduate stu-
that polydnaviral genes are active with- tobacco budworms, has discovered how dent in Lynn M. Riddiford’s laboratory
in 30 minutes of oviposition. By this the wasps fill one final chink in their at the University of Washington. There
time viral particles have spread through- immune suppression armor. Although I observed that the concentration of a
out the host, entering cells, including the cellular immune response by the key hormone regulating metamorpho-
hemocytes. In our tobacco hornworm caterpillar is essentially immediate, there sis is disturbed after parasitism of to-
system, we have also shown that at least is a lag before polydnaviral proteins are bacco hornworms by C. congregata.
one polydnavirus-encoded protein is available to alter the behavior of host The level of juvenile hormone (JH) is
produced inside host hemocytes follow-
ing parasitism. This protein is called
EP1, for “early protein 1.”
We took great care to establish that
Enlisting Insects in the War on Weeds
EP1 is in fact a polydnaviral protein.
EP1 production can be induced in to-
bacco hornworm larvae by injection of
W asps and viruses are not the only organisms capable of hardball tactics: hu-
mans are past masters. And lately scientists have turned caterpillars and their
parasites into lethal weapons against weeds. Their worthy opponent is kudzu, a fast-
polydnavirus alone, suggesting that the growing, pernicious climber that carpets seven million acres in the southern U.S.
EP1 gene resides in the genome (the Entomologist David Orr and his colleagues at North Carolina State University have re-
characteristic set of genes) of the virus; cently deployed soybean looper caterpillars to combat kudzu. In field tests the loopers
alternatively it could reside in the ge- defoliate the weed, and Orr believes the plants’ efforts to replace lost leaves will slowly
nome of the host and merely be activat- exhaust their enormous root systems (a single plant can have roots that weigh as much
ed by the virus. We deduced part of the as 300 pounds).
sequence of the gene encoding the EP1 Because soybean loopers eat crops as well as kudzu, each caterpillar enters the field
protein and then searched for this se- equipped with a safety mechanism to prevent its escape—parasitic wasps that execute
quence in various organisms. We turned the caterpillar as it spins its cocoon, ensuring that no moths will emerge to fly away and
up no such gene in Manduca but in- reproduce. An added benefit is that the parasitized loopers eat more kudzu: the wasps
stead found the EP1 gene in the polyd- extend both the feeding interval of the caterpillars and their appetite.
navirus genome. Intriguingly, manufac- It is not clear how the eggs of this wasp, Copidosoma truncatellum, escape attack by
ture of this polydnaviral-encoded pro- the immune system of the caterpillar; the wasp does not carry polydnaviruses. Several
tein correlates temporally with the most wasps that do carry polydnavirus have also been used in biological-control strategies,
dramatic effects of parasitism on host though, often as weapons against populations of pest insects, including destructive
hemocytes. fruit flies, moths and aphids. —Mia Schmiedeskamp
We detected high levels of the EP1
The Parasitic Wasp’s Secret Weapon Copyright 1997 Scientific American, Inc. Scientific American November 1997 85dramatically elevated in parasitized wasp chromosomes. No virus-free indi-
hosts, never descending to the low level viduals have ever been identified in
needed for pupation. The high levels of wasp species that carry polydna-
JH are probably caused by a lack of viruses. Virus and wasp ap-
sufficient juvenile hormone esterase, an pear to be permanent and
enzyme that clears JH from the organ- integral partners. N
HO ORM
ism. Parasitism apparently leads to sus- Unlike typical infec- R
LIF NWO AL
tained low esterase levels, in a manner tious viruses that usurp EC
YC RM
LE
that prevents pupation even after de- the replication ma-
parture of the wasps. chinery of their
It turns out that developmental arrest hosts to repro-
is largely executed by polydnavirus, al- duce wildly,
though the presence of the wasp itself is polydnavirus
needed to obtain full arrest. When we in- reproductive
ject unparasitized larvae with low doses success is af-
of polydnavirus, they fail to pupate fected by the
normally. The amount of virus required survival of each
to retard development appears to be less and every wasp. For
than that required to suppress the im- every wasp that is pro-
mune response. In fact, postdoctoral duced, a chromosomal
fellow Mitch Dushay showed that eggs copy of the virus is pro-
that have been washed prior to injec- duced. This intimate associa-
tion retain trace amounts of virus parti- tion of the genetic material of
cles or viral proteins that do not suffice wasp and virus explains the seeming-
to prevent encapsulation by immune ly selfless role of the virus in supporting
cells but may cause developmental fail- wasp parasitism. The success of polyd-
ure of the host. Polydnavirus may also navirus depends on efficient reproduc- quired the ability to copy and package
contribute to developmental effects tion of the wasp, which in turn depends a subset of useful genes selectively from
even after departure of the wasps from on an essential host-parasite relation- their own genomes, for shipment into
the host. We speculate that the virus re- ship. Any role the virus plays in ensur- caterpillar cells. Work by Webb and
mains as a latent infection in the cater- ing the success of the parasite also en- Summers on wasp venom proteins may
pillar—perhaps mediating lasting effects sures the success of viral transfer to the fit with this last hypothesis.
on development. next generation. These researchers have found that
Polydnavirus is clearly responsible Because viral transmission from wasp some wasp venom genes are similar to
for manipulating a number of develop- to wasp takes place through inheritance polydnaviral genes. Moreover, antiven-
mental and immune programs of the of a virus integrated into the chromo- om antibodies raised in the laboratory
caterpillar host in a manner that is some, there must be some other ratio- also recognize viral proteins that are im-
beneficial to the wasp. In many ways, nale for the mass production of virus in portant for manipulation of the cater-
the virus is essential to successful para- the wasp’s ovaries. In fact, the packaged pillar. It seems, then, that wasp venom
sitism. The amazing strength of this re- viruses produced at this step seem to be genes and polydnaviral genes may be
lationship between wasp and polyd- useless for the typical viral mission of evolutionarily related. This result is es-
navirus becomes even clearer when one infection with intent to replicate—but pecially exciting because certain wasp
considers the genetics of the partners. they are masters of host manipulation. venom proteins are known to play a
Viruses are expert at spreading through- supporting role in manipulating cater-
Permanent Partners out a host and entering host cells. Para- pillar physiology.
sitic wasps appear to have harnessed In one evolutionary scenario, initially
T he size and complexity of polydna-
viral genomes greatly exceeds that
of other DNA viruses: each polydna-
this talent to target useful viral protein
production to caterpillar cells, allowing
for insider manipulation of their host’s
independent polydnaviruses may have
picked up useful venom genes from the
wasp genome. In another scheme, the
virus comprises up to 28 separate circles biology. wasp may have found an incredibly ef-
of double-stranded DNA (thus their The integration of polydnaviruses ficient way to utilize its own venom
name, from “polydisperse DNA virus- into wasp chromosomes prompts ques- proteins, by copying their genes, pack-
es”). In 1986 Jo-Ann G. W. Fleming and tions about the origin of the virus. A aging them and routing them to cater-
Max D. Summers of Texas A&M dis- typical answer might be that the viruses pillar cells where they can maintain a
covered that the extremely complex originated as independent pathogens of sustained effect. Either scenario results
polydnavirus genome is integrated into the caterpillar hosts, or of the wasps in increased fitness of both the wasp
the genome of both male and female themselves, and later combined with and virus; either way the genetic bound-
wasps. This viral DNA is thought to be the wasp DNA. A much more intrigu- aries between the wasp and virus are
scattered throughout the wasp chromo- ing possibility is suggested by the ap- obscured.
somes. Wasp inheritance of the virus parently permanent and exclusive asso- Whatever the origins of the polyd-
appears to be strictly Mendelian—the ciation of viral DNA with wasp DNA. naviruses, their associations with wasps
viral sequences are copied and passed Perhaps there was never a separate viral and caterpillars offer rich opportunities
to successive generations as part of the entity. Instead wasps may have ac- for the study of evolutionary biology.
86 Scientific American November 1997 Copyright 1997 Scientific American, Inc. The Parasitic Wasp’s Secret WeaponWASP INJECTS EGGS
AND POLYDNAVIRUS WASP LARVAE EMERGE
INTO CATERPILLAR FROM CATERPILLAR
LARVA
WASP
EGG
VIRUS ENTERS
CATERPILLAR CELLS
HO IFE C
AL NW CLE
TE OR
L
L
R Y
VIRA AY VIRUS REPLICATES
RE M
H W
D
PAT IN WASP
OVARIAN CELLS
P
WAS LE
E CY C
LIF
VIRUS READY
FOR INJECTION
INTO NEW HOST
PUPA
INTERTWINING LIFE
CYCLES reveal the relations
among caterpillar, wasp and
polydnavirus. The normal horn-
worm life cycle (left) is disrupted
when a wasp injects her eggs and polyd-
navirus. The wasps mature and reproduce
normally (blue circle), but the hornworm dies prema-
turely (yellow circle, right). This sabotage is orchestrated
by polydnavirus, which enters and disables caterpillar
cells (brown circle). Wasps inherit the virus in their chro-
ROBERTO OSTI
mosomes, and the virus multiplies in the developing
wasp’s ovaries in preparation for the next round of battle.
CATERPILLAR DIES
The vicious tactics of the wasp and its Scientific American, April 1993]. between wasp and virus is so intimate
viral accomplice against their hijacked Endoparasitic wasps invariably kill that it blurs interspecies genetic bound-
caterpillar host argue against the tenu- their hosts. The event is exquisitely aries. The complex question of why the
ous hypothesis that the most highly timed and coordinated, however, to en- caterpillar does not become a moth
evolved parasites exhibit only minimal sure the success of the wasp. In beauti- should keep a raft of scientists from
virulence to their hosts [see “The Evo- ful contrast to these hardball tactics, evolutionary biologists to endocrinolo-
lution of Virulence,” by Paul W. Ewald; the mutually advantageous relationship gists busy for years to come. SA
The Author Further Reading
NANCY E. BECKAGE is associate professor of entomology at Polydnaviruses: Mutualists and Pathogens. Jo-Ann G. W. Flem-
the University of California, Riverside, where she has been on the ing in Annual Review of Entomology, Vol. 37, pages 401–426; 1992.
faculty since 1990. Her interests include the strategies adopted by How Parasitic Wasps Find Their Hosts. James H. Tumlinson, W.
parasites and pathogens to disrupt development of host species Joe Lewis and Louise E. M. Vet in Scientific American, Vol. 268, No.
and the coevolutionary relationships of host organisms with para- 3, pages 100–106; March 1993.
sites. Previously, Beckage held positions in the U.S. Department of Polydnaviruses: Potent Mediators of Host Insect Immune
Agriculture Stored Products Insects Research Unit at the Universi- Dysfunction. M. D. Lavine and N. E. Beckage in Parasitology To-
ty of Wisconsin and at the Seattle Biomedical Research Institute. day, Vol. 11, No. 10, pages 368–378; 1995.
She received a Ph.D. from the University of Washington in 1980. Parasitic Wasps. Donald L. J. Quicke. Chapman & Hall, 1997.
The Parasitic Wasp’s Secret Weapon Copyright 1997 Scientific American, Inc. Scientific American November 1997 87You can also read
