St George, T. D.

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Paper 3.20
ARBOVIRUS RESEARCH IN AUSTRALlA- VOLUME 8
EFFECTS OF THE PATHOGENESIS OF ARBOVIRUS INFECTIONS IN
CATTLE ON THE EFFICIENCIES OF VECTORS
T .D. St. George
15 
Tamarix Street, Chapel Hill, Qld 4069, Australia
In the last 50 years the number of arboviruses isolated from particular insect species has reached many
hundreds. If the insect has digested its blood meal, this is good evidence that the virus isolate has multiplied in
the insect. Of course, PCR can find virus remnants in insect species that have taken a blood meal but the viruses
may be incapable of replication within the insect tissues. There are other barriers to the insect being a valid
vector. After initial replication the virus must reach the saliva, and be delivered with the saliva into the relevant
part of the host to which it is adapted, to multiply. Usually it has a phase where it is in the bloodstream to be
taken in a blood meal for the next round of the biological cycle. There are exceptions where viruses multiply
only in surface tissues. The logistics of proVing a vector are formidable. Knowledge of the behaviour of the
virus within a vertebrate may assist the process and enable the investigator to focus limited resources more
precisely on few species.
METHOD OF FEEDING
The first problem the insect faces is to penetrate the epidermis. The mouthparts manage this action very
quickly for the flying insect's brief visit and more slowly for tick's longer contact with a vertebrate. Culicoides
midges, sandflies and ticks produce a wound through the epidermis and into the dermis. Lacerated capillaries
ooze blood into the small wound for the pool feeders to ingest. Ticks cement their mouthparts into the wound
they have produced in a fashion that varies with genera (Obenchain and Galun 1993). This prolonged contact
allows for deposition of saliva and intake of blood over a much longer period, perhaps negating the requirement
for multiplication (Jones et al. 1992) and giving an opportunity for viruses to be transmitted or acquired for days.
In contrast, mosquitoes probe for a small blood vessel and insert their mouthparts into a small blood vessel
together with much of the saliva. The mosquito does deposit some of the saliva in the dermis outside the venule
in the probing process.
The differences of feeding technique affect the fate of the arbovirus. When the virus contaminated saliva
is deposited extravascularly as with a midge or a tick it may multiply to some extent in adjacent issue cells or
those that are attracted as part of the inflammatory response. Lateral cell to cell spread does occur with certain
viruses, for example Vesicular stomatitis virus (VSV). However, to generalise within the vertebrate, it must travel
via the lymphatics to reach the bloodstream. The virus that the mosquito delivers into the bloodstream reaches its
target tissue probably well within a minute. The fate of a rhabdovirus and an orbivirus are contrasted for
illustration.
Bovine ephemeral fever virus (BEF) does not traverse the lymphatic system, at least in the first 2 dafter
viraemia commences (St.George 1993). The experiment which showed this was not continued long enough to
determine how long the lymph was free of BEF or infected neutrophils that are so characteristic of ephemeral
fever. The viraemia in experimental cases persists for 2-5 d. This is consistent with experimental findings that
the intravenous route is the only way to produce disease experimentally (Mackerras et al. 1940). Also, live virus
given intramuscularly or subcutaneously as a vaccine multiplies locally but does not generalise (Tanaka and
Inaba 1986).
In contrast, bluetongue virus (BLU) undergoes first stage multiplication within the lymph system. After
the flfSt stage of replication an increased amount of virus reaches the bloodstream and is carried to the spleen for
secondary cycle (Barratt-Boyes and MacLachlan 1994). Thus BLU is in the bloodstream from day I or 2 after
transmission and thus available to a new vector. BLU remains in the bloodstream for some weeks though not at a
titre high enough to infect a new vector via a blood meal after 2 weeks. Under experimental conditions BLU can
be injected subcutaneously, intramuscularly or intravenously and multiply satisfactorily. This applies also to
other orbiviruses which are injected experimentally (T .D. St.George unpublished data).
SIMULTANEOUS INFECTIONS IN CATTLE WITH ARBOVIRUSES
There are many possible combinations of simultaneous infections. The discussion here will be limited to a
few examples. If closely related viruses infect a cow at the same time this gives a chance for exchange of genetic
information.
Paper 3.20
ARBOVIRUS RESEARCH IN AUSTRALfA- VOLUME 8
For example, Akabane and Aino viruses have been isolated from a single blood sample from a bull
(Cybinski and Zakrzewski 1983). When two viruses of very different families enter a cow from vectors one may
block the other. St. George (1985) bled 22 cattle daily during a 3 week period during an ephemeral fever
epidemic. Six arboviruses, besides BEF, infected one or more of the group in the observational period. Only six
of 22 fully susceptible cattle developed clinical ephemeral fever during this time. These were also the only cattle
from which BEF was isolated and which seroconverted to BEF. There were no subclinical infections. Four of
the seven had pre-existing immunity to CSIRO Village virus (CV), an orbivirus which produces a subclinical
infection in cattle. In the other three -cattle with ephemeral fever, where the viraemia with CV began shortly after
BEF infection, the duration of viraemia with CV appeared to be shortened.
Of the remainder in the group CV established a viraemia of 12 to 17 d which appeared to block BEF
infection in 10 of the other 15 cattle and other arboviruses (Akabane, Aino, Peaton, Douglas, Tinaroo and
Kimberley viruses) in the remaining 5. All the cattle that did not develop BEF infection and clinical ephemeral
fever, because of the interference by the other arboviruses, were susceptible in the next epidemic 2 years later
(St. George 1985).
It appears that the first virus to establish and multiply has successfully blocked the other. In this instance,
the outbreak of ephemeral fever was halted while susceptible animals remained. The rhabdovirus BEF which
goes directly into the bloodstream is competing with an orbivirus (CV virus) which presumably replicates in the
lymph system first in a similar fashion to BLU. Both viruses are from types which induce interferon
(interleukins) production by the host tissue (Eksteen and Huismans 1972, St. George et al. 1986, Uren and
Zakrzewski 1989). Interleukins, being soluble, would be in the lymph as well as in the plasma.
In the outbreak of Tammar Wallaby Disease (Kirkland et al. 2000), there was a high mortality in
wallabies. However, no homologous antibody was found in wallabies that did not die. It is possible that
infection by the newly identified orbivirus was blocked by one or other of the arboviruses that are also carried by
Cu/icoides vectors (for example, Wallal or Warrego virus).
TARGETING VECTORS
How can knowledge of route of infection help to narrow the search for a vector? In the case of BLU, 52
species of insect were listed by Gibbs and Greiner (1988) as potential vectors. As these were all Cu/icoides
species there is no advantage from knowledge of the pathogenesis within the vertebrate host. However, in the
case of the rhabdovirus, BEF has been isolated from mosquitoes and Cu/icoides (Table 1). If the insects that rely
on pool feeding are eliminated, the three Cu/icoides species, from which BEF has been isolated, are eliminated.
This leaves the mosquitoes. Both Culicine and Anopheline mosquitoes are represented in Table 1 as sources of
BEF. This means that all mosquito species biting cattle are suspect. Additional species of mosquito must be
found to cover the vast range of Africa, Asia and Australia that ephemeral fever is found, beyond the range of
these species. However, the false trail which has wasted effort by processing hundreds of thousands of
Cu/icoides species for BEF, can be avoided in the future.
Table Which are the vectors?
-
Mosouito and Culicoides snecies
There is other evidence that can be advanced to support the evidence from pathogenesis studies that
mosquitoes are vectors of ephemeral fever and not Cu/icoides. Experimental ephemeral fever is produced reliably
only by the intravenous injection of virulent virus (Mackerras et al. 1940).
Paper 3.20
ARBOVIRUS RESEARCH IN AUSTRALlA- VOLUME 8
The epidemiology of ephemeral fever in Australia is not consistent with C. brevitarsis Kieffer being a
vector (St. George 1993, Kirkland 1993). After experimental infection of C. brevitarsis and Culex annulirostris
Skuse with BEF, only the mosquito excreted BEF in saliva (Muller 1987, Muller pers comm). KIM virus that is
closely related to BEF has been isolated from Cx. annu/irostris as well as C. brevitarsis. Thus, in Australia, Cx
annu/irostris should be a prime target in the search for vectors of ephemeral fever using techniques not available
before the 1990's with considerable economy of effort. Strategies for control of vectors can also be more
rationally based on the natural history of mosquitoes rather than Culicoides.
There are other instances where rhabdoviruses have been isolated from both mosquitoes and Cu/icoides
midges. Fukuoka virus has been isolated in Japan from Cx. tritaeniorhynchus Giles and C. punctatus (Kaneko et
al. 1986). Oakvale virus has been isolated from Cx. edwardsi and C. austropa/pa/isLee and Reye, both bird
feeding insects in Australia. If there is a need to determine the vectors of these viruses initial effort should be
focussed on the mosquito species.
AN HYPOTHESIS WITH WIDER IMPLICATIONS
The Rhabdoviridae are a diverse group of viruses. Not all are arboviruses. Rabies virus, the type species,
is spread by the bite of a mammal. The pathogenesis is very well understood. This virus and its close relatives
traverse the neural system and then reach the salivary glands of the vertebrate host and not the lymphatics to
complete their life cycle. Vesicular stomatitis virus spreads laterally in skin tissue and does not generalise from a
local infection (Wilks 1994, TM Monath pers comm). To these two very different rhabdoviruses, BEF can be
added. Thus, within the rhabdoviridae, it may be a characteristic of the family that multiplication with the lymph
system is not a part of their natural history. They have exploited different pathways in their successful biological
cycles.
REFERENCES
Barratt-Boyes SM and MacLachlan NJ (1994) Dynamics of viral spread in bluetongue virus infected calves. Vet
Microbiol40: 361-371.
Cybinski DH and Zakrzewski H (1983) A dual infection with Akabane and Aino viruses. Aust Vet J 60: 283.
Eksteen PAL and Huismans H (1972) Interferon induction by bluetongue virus and bluetongue virus ribonucleic
acid. Onderstepoort JVet Res 39: 125-132.
Gibbs EPJ and Greiner EC (1988) Bluetongue and epizootic hemorrhagic disease. In: The arboviruses:
epidemiology and ecology. Vol. 11 (Monath TP, Ed) CRC Press, Boca Raton. pp.39-70.
Jones LD, Kaufman DK and Nuttall PA (1992) Modification of the skin feeding site by tick saliva mediates virus
transmission. Experientia 48: 779-782.
Kaneko N, Inaba Y, Akashi H, Muira Y, Shorthose J and Kurashige K (1986) Isolation of a new bovine
ephemeral fever virus. Aust Vet J 63: 29.
Kirkland PD, Davis RJ, Rose K, Cooper D and Blumstein D (2000) Isolation of orbiviruses during an epizootic
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Uren MF, YoungPL and HoffmannD, Eds) pp. 33-37.
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Effects of the pathogenesis of arbovirus infections in cattle on the efficiencies of vectors

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Effects of the pathogenesis of arbovirus infections in cattle on the efficiencies of vectors

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