....
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Antiviral Chemistry & Chemotherapy (1992) 3(6), 311-326
Review
Prospects for antiviral chemotherapy in veterinary
medicine: 2. Avian, piscine, canine, porcine, bovine and
equine virus diseases*
E. A. Rollinson
Pitman Moore Europe, Breakspear Road South,
Harefield, Uxbridge UB9 6LS, UK.
Summary
This paper, which is published in two parts, reviews
the literature pertaining to antiviral chemotherapy of
viruses of veterinary importance. While early reports in
the 1970s referred to the chemotherapy of a number of
different RNA and DNA viruses, there' was consider-
able focus in the 1980s, initially on herpesviruses and
latterly on retroviruses, and particularly in cats. Details
are given of the successful treatments of FeLV and FIV,
which have been used as animal models for HIV
therapy. 'Therapy of equine, canine, bovine, porcine,
avian, and fish diseases is also considered. The high
costs of developing and registering a new chemical
entity, especially for food species in which extensive
toxicity/residue data are required, is the main reason
why specific antiviral compounds are not currently
available for veterinary use, although some non-speci-
fic immune modulators are now emerging. Concurrent
availability of appropriate diagnostic tools is a prere-
quisite for successful veterinary antiviral chemo-
therapy, as is a greater understanding of the
pathogenesis of virus infections in animals and the
development of more sophisticated means of drug
delivery, appropriate to both food animal species and
companion animals (dogs, cats, and horses).
Additionally, antiviral agents are valuable as research
tools per se, as opposed to solely as chemotherapeu-
tic agents. Part 1 covers the feline virus diseases, while
part 2 includes the other viruses ~f veterinary import-
ance, in dogs, horses, cattle, pigs, birds, and fish.
Introduction
Antiviral chemotherapy in the veterinary field remains at
Received 26 March, 1992; revised and accepted 8 May, 1992. For
correspondence. Tel. 0895 626 303; Fax. 0895626 476.
• Part 1, 'Feline virus diseases' was published in Antiviral Chemistry &
Chemotherapy 3(5).
the early stages of development, although it is almost 30
years since the concept of antiviral chemotherapy became
an actuality. While a number are available for the treatment
of virus infections in humans, to date, no specific antiviral
compounds have been licensed solely for veterinary use.
Indeed, compounds such as acyclovir (Zovirax®) and
zidovudine (Retrovir®) have been so successful, that they
now represent some 43% of total sales of The Wellcome
Foundation pic, with turnovers for the half-year to Feb-
ruary 1992 of £278 million for Zovirax'" and £103 million for
Retrovir®,up over 30% on 1991 (Anon, 1992b). In humans,
. antivirals are almost exclusively restricted to treatment of
herpes or retrovirus infections.
The two main reasons for the absence of antiviral drugs
for veterinary use is the high cost of development coupled
with narrow spectrum of activity. There has been a lack of
investment in targeted antiviral research programmes in
animal health, because of the likely poor return on such
investment. The development of a new chemical entity,
particularly for use in food species, costs in the region of
£10 million and takes approximately 10 years, because of
the extensive safety/toxicity/residue testing required for
product registration. While this investment may be justi-
fied for a broad spectrum antibacterial which can be used
in several different species against a number of diseases,
it is unlikely to be so for an antiviral compound, which
could be useful against a single virus in a restricted
number of species.
The concept of a really 'broad spectrum antiviral' (other
than non-specific immunomodulators or cytokines) will be
difficult to realize since, to date, a broader spectrum of
action has normally been associated with host cell toxicity.
For example, while acyclovir (ACV) had good activity
against equine herpes virus 1 (EHV-1), only poor activity
was reported against the other herpes viruses of domestic
animals, SHV-1 (porcine), BHV-1 [bovine), FHV-1 (feline)
(Rollinson and White, 1983), and acyclovir shows no
activity against other DNA viruses or against RNA viruses
such as TGE, transmissible gastoenteritis, a member of
the Coronaviridae (Rollinson, 1988). However, the advent
of compounds such as HPMPA and HPMPC, which do
have a relatively broad spectrum of activity but low
toxicity, is encouraging.
312 E. A. Rollinson
The specificity of action of acyclovir, and similar nucleo-
side analogues, is due to the fact that such compounds
require conversion to the active triphosphate form within
virus-infected cells. The phosphorylation to the mono-
and/or diphosphate is catalysed by the virus-specified
thymidine kinase (TK). The ACV triphosphate then acts as
a substrate for viral DNA polymerase and inhibits further
DNA synthesis by chain termination. The relatively low
sensitivity of BHV-1 to acyclovir results from the nucleo-
side analogue not being a good substrate for the viral TK
(Weinmaster et al., 1982).
Evenif specific veterinary antivirals were available, there
remains a practical problem in the timing of treatment.
Generally, by the time clinical signs of virus infection are
apparent, in acute infection at least, and the disease has
been diagnosed, much of the viral replication and conse-
quent pathological changes will have already taken place.
In these cases, antiviral chemotherapy is likely to be of
limited value, except in in-contact animals not yet showing
signs, and symptomatic therapy is likely to be the only
practical approach. However, this limitation used to be
attributed to human antivirals, and has since been proved
untenable. The importance of rapid, specific diagnostic
tools as a fundamental basis of antiviral therapy cannot be
stressed too strongly. Although, there is currently much
effort in this field, the emphasis is on development of
diagnostics to accompany viral vaccines, either to ascer-
tain whether vaccination is necessary or has been
successful, rather than for the diagnosis of infections.
Notwithstanding the above reservations, the research
effort on the human front has greatly intensified since the
advent of HIV (human immunodeficiency virus) and AIDS
(acquired immunodeficiency syndrome) and the search for
anti-retroviral drugs is likely to lead to the discovery of
potential compounds for veterinary use. Furthermore,
animals models e.g. FeLV and FIV are being used in the
screening process for human antivirals. In two parts, this
paper provides an update on earlier reviews (Gustafson,
1980; White, 1981; Rollinson, 1988) and will demonstrate
how the initiatives in human antiviral research will impact
on the prospects for the veterinary field. There are
innumerable reports of activity in vitro of many antivirals
against viruses which are only of veterinary importance
(see Rollinson, 1988) as well as reports where antiviral
agents have been used solely as research tools per se.
While referring to in vitro activity where appropriate. this
review will be largely restricted to reports of in vivo testing.
Summary tables are given, by species, listing the virus
diseases against which antiviral agents have been tested
in vivo in the target host, together with the compounds
tested and their actlvlties, as follows: In part 1,Table 1A on
feline diseases, followed in part 2 by: Table 1B, avian
diseases; Table 1C, bovine diseases; Table 1D, porcine
diseases; Table 1E, equine diseases; Table ,1 F, canine
diseases; and Table 1G, fish diseases. Details of these
reports are given in the text, with the emphasis on
retroviruses and herpesviruses, reflecting the relatively
large effort in these areas. Apart from a brief mention by
White (1981) of a lack of activity of the antipox drug
methisazone against orf infection, there are no reports of
testing antivirals against ovine viruses in sheep, although
visna virus has been used as an in vitro model for HIV
(Frank et al., 1987). However, there are two reports of
sheep being used as a model in vivo system for testing
suramin against bovine leukaemia virus, to which sheep
are susceptible (Burkhardt and Ros, 1989; Rosenthal et
al., 1990). Prior to doing studies in the target host,
dose-ranging work is frequently done in laboratory animal
models. The currently available models for viruses of
veterinary importance are listed in Table 2, part 2 together
with the compounds tested and their relative activities. It is
of interest to note that there is not always good correlation
between these models and activity in the target species. A
review of several animal models used to assess human
antivirals is given by Field and Brown (1989).
Avian herpesviruses
A review on the significance of antiviral chemotherapy to
the poultry industry is given by Gustafson (1980). The
avian herpesviruses include Marek's disease virus (MDV),
Turkey herpes virus (THV), Pigeon herpes virus (PHV),
Duck plague herpes virus (DPHV). In vitro studies with
compounds which have shown activity are as follows: (1)
Pyrophosphate analogues. Slight activity against DPHV
(R. Olson et el., personal communication), PHV (Schwers
et al., 1980, 1981), but moderate activity against MDVand
THV (Reno et aI., 1978), (2) Ribavirin. Moderate activity
against MDV (C. S. Edison, p~rsonal communication;
Eidson et el., 1974), (3) Acyclovir. Slight activity against
PHV (Thiry et al., 1983), with moderate activity against
MDV and THV (Collins, 1983), and (4) Fluoropyrimidine
nucleosides (FIAC, FMAU, FIAU). High activity against
MDV and THV (Schat et el., 1984).
In vivo studies in the target species (see Table 1A) have
been disappointing with phosphonoacetic acid (PAA) and
MDV (Lee et al., 1976) and Phosphonoformic acid (PFA)
and PHV (Vindevogel et aI., 1982). No positive effect was
demonstrated in Marek's disease-infected chicks treated
for 28 days at 500mg PAA kg- 1 day" i.p, or in pigeon
herpesvirus-infected pigeons and budgerigars treated for
10 days at 1OOmg PFA kg- 1 day" i.rn, PHV infection also
proved refractory to acyclovir treatment [100mg kg- 1
day-1, i.rn., thrice daily] (Thiry et al., 1983) and MDV
infection was not ameliorated by the interferon inducer,
Poly I:C (Nemes et aI., 1969). Cyclophospharnlde gave
some protection «30%) against MDV in chickens (Lu et
al. 1976; Yue-Shoung et et., 1976).
 Antiviral chemistry in veterinary medicine 313

Table 18. Avian virus diseases against which

antiviral agents have been tested in vivo in Virus/disease Compound Activity Reference
chickens and turkeys.
Avian
Avian influenza Amantadine +++ Lang et at. (1970)
(turkeys) +++ D. Karunakaran (personal
communication)
Avian influenza Amantadine ++ Webster et at. (1985)
(chickens) Webster et at. (1986)
Avian influenza amino-caproic acid
(chickens) and aprotinin ++ Zhirnov et at. (1983)
Avian influenza Polyl:C Portnoy and Merigan (1971)
(chickens) Statolon ++
Tilorone
ExogenouslFN ++
Marek's Disease Phosphonoacetic acid Lee et at. (1976)
Ribavirin ++ C. S. Eidson et at. (personal
communication; 1974)
aminoureidophenyl ++ Eidson et at. (1974)
sulphone Chang (1973,1974)
dichlorodiphenyl- ++ Colrnano et at. (1971)
dichloroethane
Polyl:C Nemes et at. (1969)
Acyclovir + Salamonowicz et at. (1987)
cyclophosphamide + Lu et al. (1976); Yue-Shoung
et at. (1976)
statolon ++ V. E. Vengris and C. J. Mare
(personal communication)
exogenouslFN ++ V. E. Vengris and C. J. Mare
(personal communication)
Arginine/lysine Chang et al. (1982)
Pigeon herpes phosphonoformic acid Vindevogel et at. (1982)
acyclovir Thiry et at. (1983)
Newcastle Disease
(chickens) ribavirin ++ Anjum et al. (1982)
isoprinosine + Moya et at. (1984)
butylated
hydroxytoluene ++ Brugh (1977)
impacarzin +++ E. F. Kaleta et at.
(personal communication)
Haemorrhagic
Enteritis
(turkeys) metyrapone ++ Colmano et al. (1971)
Myeloblastosis adriamycin Dhananjaya and Antony
(chickens) (1988)

Table 1C. Bovine virus diseases against which

antiviral agents have been tested in vivo in cattle. Virus/disease Compound Activity Reference

Infectious Bovine bromovinyl-deoxyuridine Babiuk et at. (1983)

Rhinotracheitis 2-deoxyglucose + Mohanty et at. (1980)
(IBR) (BHV-1) Polyl:C ++ Theil et at. (1971)
(IPV) aminobromophenyl- ++ Hamdy and Stringfellow (1980)
pyrimidol
Hu-IFNa2 -1+ C. van den Broecke et at.
(personal communication)
BOV-IFN-a1 Babiuk and Bielefeldt Ohmann
(1984)
Czarniecki et at. (1985)
BOV-IFN-a1 + Babiuk et at. (1984,1985)
Levamisole Bielefeldt Ohmann et at.
(1987)
BOV-IFN-a1 + Lawman et at. (1987)
HPMPC +++ Gilliam and Field (1992a, 1992b)
Bovine rotavirus Hu-IFN-a2 ++ Schwers et at. (1984)
van den Broecke et at. (1984)
Bielefeldt Ohmann et at.
(1987)
Bovine leukaemia cyclophosphamide Van der Maaten et at.
(1984)
Bovine respiratory 2-deoxyglucose + Mohanty et at. (1981)
syncytial (RSV)
314 E. A. Rollinson

Table 1D. Porcine virus diseases against which

antiviral agents have been tested in vivo in pigs. Virus/disease Compound Activity Reference

Aujeszky's Disease
(SHV-1) phosphonoacetic acid + Gustafson and Scherba
(pseudorabies) (1977)
ara-AMP + COV ++ D. P. Gustafson et al.
(personal communication)
bromovinyl- + Rollinson (1988)
deoxyuridine
DHPG + Rollinson and White (1988)
Isoprinosine Glasgow and Galasso
(1972)
Porcine Influenza 6-azauridine Steffenhagen et a/.
(1976)
idoxuridine +
(toxic) Steffenhagen et a/.
(1976)
Transmissible 6-azauridine Steffenhagen et a/.
gastroenteritis (1976)
(fGE) idoxuridine Glasgow and Galasso
isoprinosine (1972)

Table 1E. Equine virus diseases against which

antiviral agents have been tested in vivo in Virus/disease Compound Activity Reference
horses.
Equine Influenza amantadine ++ Bryans et a/. (1966)
Infectious
anaemia morpholino-biguanide Tabuchi and Akiyama
(1973)
EHV-1 (herpes) DHPG ++ Rollinson and White
(rhinopneumonitis) acyclovir (unpublished observations)
(adverse
reactions)
HPMPC ++ Gibson et a/., (1992)
(keratitis) IDU +++ Matthews and
Handscombe (1983)

Table 1F. Canine virus diseases against which

antiviral agents have been tested in vivo in dogs. Virus/disease Compound Activity Reference

Infectious canine nialamide +++ Cifuentes-Bernal et a/.

hepatitis (CAl/) (1968)
polyl:C + Wooley et a/. (1974)
Distemper diethyl ether +++ Donovan (1968)
(inhaled)

Table 1G. Fish virus diseases against which

Virus/disease Compound Activity Reference
antiviral agents have been tested in vivo in trout
and salmon.
Infectious
pancreatic
necrosis (trout) ribavirin Savan and Dobos (1980)
polyvinyl-
pyrrolidoneiodine ++ Econonom (1973)
Oncorynchus masou
(salmon) idoxuridine ++ Kimura etal. (1983b)
acyclovir + Kimura et a/. (1983b)
Infectious
haematopoietic 1-~-D-ribofuranoyl- + Hasobe and Saneyoshi
necrosis (trout) 5-hydroxyuracil (1985a, 1985b)

Moderate activity in vivo against MOV was obtained
with amino-ureidophenylsulphone (Chang, 1973, 1974;
Eidson et al., 1974), with dichlorodiphenyldichloroethane
(Colmano and Gross, 1971), with Statolon and with
exogenous IFN (V. E. Vengris and C. J. Mare, personal
communication). A study of the effects of in-feed amino
acids lysine and argenine, which, respectively, have been
reported to suppress the clinical manifestations of
herpesvirus infections and enhance multiplication of
herpesviruses, was undertaken in chickens infected with
MOV, but no details have been published. Ribavirin was
effective in reducing lesions in MOV experimentally
infected chickens when administered s.c, (500mg kg- 1
day:", twice daily injections for 2 weeks), but was inef-
fective when provided in feed (1 g 1001b- 1 feed) to
1-day-old chickens for 6 weeks (C. S. Eidson, personal
communication; Eidson etal., 1974). Repeated parenteral
treatment of communally reared chickens would not be
economically feasible and it is unlikely that ribavirin would
become a commercial reality for control of Marek's
disease. Various other agents have been tested for their
antiviral activity in poultry. Treatment with the two adrenal
steroid-blocking agents, metyrapone and dlchlorodiphe-
nyldichloroethane in feed (350 and 500mg kg-1,
respectively), significantly reduced the severity of disease
in herpes encephalitis virus-infected turkeys and Marek's
disease virus-infected chickens, respectively (Colmano
and Gross, 1971).There are no reports of chemotherapeu-
tics providing over 80% protection in avian species with
herpesvirus infections.
Other avian viruses
A report on the promising prophylactic activity of amanta-
dine appeared in,970 against malignant influenza A in
turkeys (Lang et aI., 1970). Optimum effectiveness was
obtained only with sustained administration of the drug
over a 2-3 week period; infection was prevented, or
remained subclinical, in about 80% of turkeys given a
single oral dose (10mg kg- 1) or when amantadine was
incorporated into the feed pellets at 0.025 or 0:05%
(:::;5mg kg- 1 day-1). The minimum effective dose was of
the order of 5 mg kg- 1, giving 10-20% failures.
Studies on the efficacy of amantadine_against influenza
A virus infection in quail were reported by Easterday
(1975), but it was not until 10 years later that another
publication on its use in poultry appeared. Webster and
co-workers (1985) showed that amantadine and rimanta-
dine administered in drinking water (0.1 or 0.01%) were
efficacious both prophylactically and therapeutically
against an influenza A virus infection in chickens, which
caused up to 80% mortality. However, under conditions
simulating natural transmission of the virus, amantadine-
resistant mutant viruses arose within 9 days: all of the
Antiviral chemistry in veterinary medicine 315
contacts were infected and approximately 50% died.
Simultaneous administration of H5N2 vaccine and aman-
tadine protected birds from infection, whereas vaccine
alone did not. The efficacy of vaccine plus chemo-
therapeutic agent can be explained by the rapid response
of chickens to vaccination with influenza virus. By the time
amantadine-resistant viruses appeared (approximately 9
days after initial infection), the birds were immune. These
results indicate that, should a highly virulent influenza
outbreak appear, amantadine plus vaccine would be
feasible, especially when eradication is not a viable option.
In turkeys, amantadine was most effective when adminis-
tered orally for at least two days after challenge (D.
Karunakaran, personal communication). The protease
inhibitors E-amino-H-caproic acid and aprotinin, when
administered to influenza virus-infected chicks (every
3-6h i.rn. for 3 days), prevented the development of a
generalized infection when therapy was commenced
immediately (Zhirnov et el., 1983). Moreover, when
therapy was commenced 72 h post-infection, it blocked
an already disseminated infection.
Newcastle DiseaseVirus (NOV) infection in chickens has
provided another target for chemotherapy studies. Riba-
virin proved effective in reducing mortality when adminis-
tered orally (by gavage or in drinking water) to infected
flocks of chickens in Pakistan (Anjum et al., 1982).
Treatment had no curative effect on severely affected
birds, but did prolong their survival time. Ascorbic acid
was inactive in vivo in NOV-infected chickens (Kramer et
aI., 1973). In pilot trials, the imidazolidone derivative
Impacarzin, injected i.rn., prevented the development of
clinical signs and mortality in NOV-infected chicks and
adult chickens (E. F. Kaleta et al., personal communica-
tion). The therapeutic effect was dependent on the virus
challenge and dose rate and also on the time interval
between infection and treatment. In a study aimed at
explaining why NOVvaccines sometimes fail to immunize
recipient birds, it was found that butylated hydroxytoluene
(BHl), a widely used antioxidant poultry feed additive,
incorporated in diet at 100-200 ppm, prevented mortality
of chickens exposed to virulent NOV and also prevented
the serological response of chickens exposed to avirulent
vaccine NOV(Brugh, 1977). It was considered premature,
on the basis of this study, to consider the clinical use of
BHT for control of NOV, and important first to define the
mechanism of apparent antiviral action of BHT.
Whitfill et al. (1991)reported on what appears to be one
of a newly identified class of non-specific antiviral agents
produced in vivo in chickens in response to viral infection,
with activity against NOV, infectious bursal disease virus,
and infectious bronchitis virus. The virus neutralizing
factor (VNF) acts as an in-contact inhibitor, rather than at
the cellular level to prevent viral replication, ruling out that
it is an IFN-agent. However, protective effects of VNF were
316 E. A. Rollinson

not observed when given to chickens immediately, before,
or 3 or 7 days prior to Rous sarcoma virus challenge.
The liver disease associated with Duck hepatitis B virus
(DHBV) infection of domestic ducks provides a useful
model for the human counterpart (Marion et aI., 1984), but
reports of antiviral activity against DHBV appear to be
limited to in vitro studies (yokota et al., 1990). Of a number
of nucleoside analogues tested, (S)-HPMPA showed the
highest activity, ICso 0.511-g mr',
not investigated, and no further studies with this
compound have been reported.
Hasobe and Saneyoshi (1985a) reported on the treat-
ment ofthe rhabdovirus infectious hematopoietic necrosis
virus (IHNV) in salmonid fishes by 6-TI (6-thioinosine)
(O.111-g rnl") and 5-0HUrd (10 I1-g rnr') (1-[3-D-ribofura-
nosyl-5-hydroxyuracil), over a four-week period, either
daily or on alternate days. The compounds were moder-
ately effective, with life span increased in treated groups,
with survival rates 26% and 20% higher, respectively.
5-0HUrd was less effective when given on alternate days.

Piscine viruses
Canine viruses
The fish herpesviruses include Herpes virus salmonis
DHPG was inactive in vitro against canine herpesvirus
(HVS), Oncorhynchus masou virus (OMV), and channel
(CHV) (Smith et aI., 1983; Ogilvie and Hanna, 1984).
catfish virus (CCV). No activity against HVS and OMV was
Ribavirin showed high activity in vitro against canine
reported in in vitro studies with Ara-A (Kimura et el., 1983a)
parainfluenza virus (Povey, 1978).
but CCV proved very susceptible (ICso <10 I1-M) (Buck and
Isoprinosine was inactive in ferrets infected with canine
LOh, 1985). The pyrophosphate analogues showed slight
distemper virus (Glasgow and Galasso, 1972), while
activity in vitro against CCV and moderate activity against
diethyl ether (inhaled) showed high activity (Donovan,
OMV (Koment and Haines, 1978; Kimura et al., 1983a;
1968).
Buck and LOh, 1985). Idoxuridine and acyclovir on the
Subcutaneous administration to dogs of poly I:C (0.2mg
other hand, were highly active in vitro, (ICso <10 I1-M)
kg- 1) 24h before i.v, inoculation of infectious canine
against CCV, OMV, and HVS and in vivo against OMV
hepatitis virus resulted only in longer survival of the treated
(Kimura et al., 1983b). When IDU was provided in feed at a
compared with the untreated dogs (a mean survival time of
dose rate of 2511-g per fish per day for 60 days, or when fish
6.1 and 3.8 days, respectively) and no dogs survived
were placed in water containing 2511-g IDU mr' mortality
(Wooley et aI., 1974). The poor protection recorded may
was delayed and reduced and tumour development
have been due to the fact that circulating IFN was not
markedly suppressed. The effect of ACV in reducing
detectable in the dogs. The route of administration of the
mortality and preventing tumour development in OMV-
IFN inducer may greatly affect the IFN response. Thus, it
infected chum salmon fry was only evident when the fry
cannot be argued that the IFN per se was ineffective, but
were immersed in a 2511-g ACV rnr ' solution (30 min day"
rather the inducer was ineffective in promoting an ade-
for 15-60 days), and was not seen in fish receiving
quate IFN response. The monoamine oxidase inhibitor
ACV-medicated food (approximately 2511-g per fish per
nialamide (50mg kg- 1 , in divided, thrice daily oral doses)
day), which is the preferred method of giving medication in
was of therapeutic value in the treatment of experimental
practice.
infectious canine hepatitis virus infection in dogs as
A single 2-h exposure of infectious pancreatic necrosis
determined by clinical signs, liver function tests, and
virus (IPN)-infected fry to ribavirin doses as high as 400 I1-g
histopathology (Cifuentes-Bernal et aI., 1968).
mr' tank water resulted in only a slight decrease in the Although there are reports on activity against rabies
number of deaths (Savan and Dobos, 1980). Whether
virus in vitro (e.g. Tsiang et aI., 1978, 1991; Hernandez-
repeated daily exposure of the fry would have produced
Jaurequi et al., 1980) and in laboratory animals (Table 2),
better results was not investigated because, in a hatchery
there do not appear to be any data or in vivo work in dogs.
situation where the numbers of fish and size of tanks are so
Therapy of viral-infections of the central nervous system is
large, the cost of such a measure would be prohibitive.
covered by Griffin (1991).
In 1962, Economon showed that young brook trout that
were fed polyvinylpyrrolidone-iodine (PVP-I) in their food
Porcine viruses
ration showed a significant reduction in IPN morbidity and
mortality. SUbsequent studies to determine the optimum Transmissible gastroenteritis virus (TGEV) was reported to
dose regimen were not reported until 10 years later be insensitive in vitro to amantadine (Dimitrov, 1983; E.R.
(Economon, 1973). Brook trout fry were given PVP-I Rollinson, unpublished observations) the pyrophosphate
treated diet for 15 days to give an estimated intake of 1.64 analogues PFA and PM (Dimitrov, 1983; E.R. Rollinson,
available iodine kg day", A mortality of 17% was unpublished observations) leupeptin (Appleyard and Tis-
observed in the treated fish compared with 34% mortality dale, 1985) and the fluoropyrimidine nucleosides, FIAC,
in the untreated controls. The mode of action of PVP-I was FMAU, FIAU (E.R. ROllinson, unpublished observations).

However, Ribavirin showed moderate activity in vitro (IC50
10-100 f.1M) (Krainova et aI., 1983).
In pigs with TGEV infection, idoxuridine or 6-azauridine
treatment was ineffective (Steffenhagen et aI., 1976), as
was isoprinosine (Glasgow and Galasso, 1972).
In studies against pseudorabies (Aujeszky's disease,
SHV-1)in pigs (D. P. Gustafsen et al., personal communi-
cation) the highly soluble monophosphate ester disodium
salt of Ara-A, Ara-AMP, was used (10 or 20mg kg- 1 i.rn,
every 8 or 24 h for 5 days) together with the adenosine
deaminase inhibitor co-vidarabine (Co-V) (one injection
i.m. prior to first Ara-AMP) dose. Although all piglets
developed pyrexia and exhibited some degree of nervous
system involvement attributable to the virus, treatment did
delay the time of onset of clinical signs, but Co-V did little
to enhance the effectiveness of Ara-AMP, as all the piglets
in this group died.
Further work on experimentalBl-iv-t infection was
reported by Rollinson et al. (1988). Two experimental
porcine models of SHV-1 were compared for assessing
the efficacy of a nucleoside analogue, BW B759U (9-[1,3-
dihydroxy-2-propoxymethyl] quanine, DHPG. While signs
were the same following intranasal inoculation and in-con-
tact transmission of SHV~1 , the time-course of the disease
was different. There was less variation in clinical signs
between pigs following artificial infection, but the disease
was more severe, making this a consistent but also more
stringent test system. DHPG was administered intramu-
scularly in divided twice daily doses at 50 mg kg- 1 to
three-week-old piglets in these two SHV-1 disease
models. In artificially infected animals, in which treatment
was begun 1.5h preinfection and continued for six days,
there was a delay in the onset of clinical signs (4.8
compared with 3.2 days), a 1 log10 reduction in virus
shedding, and a 1 to 2 log10 reduction in Virus recovered
from tissues, but all the treated piglets died from AD. In
contrast, none of the DHPG treated piglets in the in-con-
tact model system died during the eight-day medication
period, although two piglets died subsequently. Mean
serum concentrations of DHPG 2 h after intramuscular
dosing were about 45 f.1M, at 9 h 15-20 f.1M and at 17 h
3.5 f.1M. The in vitro IC50 of DHPG against SHV-1 varied
from 1.5 to 80 f.1M depending on the cell line in which the
assay was carried out. There were no overt signs of DHPG
toxicity in the treated piglets.
While the porcine rotaviruses were insensitive in vitro to
ribavirin, bovine rotavirus proved moderately sensitive
(IC50 10-100 f.1M) and Rotavirus from both cattle and pigs
were moderately sensitive to DHPA (D. F. Smee et aI.,
personal communication; R. W. Sidwell et aI., personal
communication). Bovine rotavirus was insensitive to
HPA-23 in vitro (Evrard etal., 1984), but moderately
sensitive to HulFNu 2 (Dagenais et aI., 1981; Schwers et
al.,1985).
Antiviral chemistry in veterinary medicine 317
African swine fever virus has been the subject of
numerous in vitro studies (reviewed by Gil-Fernandez et
aI., 1987), but there do not appear to be any published
reports of studies in pigs. A system for the larqe-scale
production of purified mature recombinant porcine IFN-u
has been described recently (Lefevre et aI., 1990). The
availability of this molecule will open up a new field for in
vivo investigations concerning the role of IFN in pigs and
its possible prophylactic use.
Bovine viruses
In vivo studies in cattle on therapy of bovine rotaviruses
include those with HulFN 2, which showed moderate
protection (A. Schwers et al., personal communication;
van den Broecke et al., 1984; Schwers et al., 1985).
Bacterially produced HulFN was administered at a rate of
106 IU kg- 1, l.m., daily for 3 or 4 days, to three colostrum-
deprived calves inoculated orally 2-24 h post birth with
approximately 108 p.f.u. rotavirus (strain 81/36F). Two
treated calves remained clinically normal and one pre-
sented with transient diarrhoea only, while in the four
untreated controls, diarrhoea persisted for at least 48 h
and one calf died. Equivocal results were obtained when
Hu-IFN was tested against BHV-1 in cattle. A dose of 106
IU kg- 1 was, administered l.rn, for 6 days to 3 heifers,
commencing 24 h prior to intranasal infection with 5 x 107
p.f.u. BHV-1. Treatment did not reduce virus excretion or
nasal discharge, and did not prevent the establishment of
latency (C. van den Broecke et aI., personal communi-
cation).
Babiuk and co-workers have investigated the potential
of recombinant bovine interferon alpha (BoIFNu) against
the viruses implicated in bovine respiratory disease.
Treatment of bovine alveolar macropahges or polymor-
phonuclear granulocytes with BolFNu resulted in reduced
BHV-1 replication and spread (Bielefeldt Ohmann et al.,
1984; Babiuk et al., 1984). The increase in leukocyte
function was not always apparent; in some instances, the
random and chemotaxin-induced migration of cells were
suppressed. Of the other bovine viruses against which
BolFNu has been tested in vitro, vesicular stomatitis virus
proved the most susceptible (inhibited by 1 to 10 IU rnl"),
followed by bovine virus diarrhoea virus (1 031U rnr') and
parainfluenza-3 virus (1621U mr'), with BHV-1 being the
least susceptible (>1000 IU mr') (Czarniecki et al., 1985).
In in vivo experiments, treatment of calves (groups of 5)
with BolFNu (10 or 25 mg per animal) had a definite effect
on their ability to withstand a virulent challenge 48 h later
with BHV-1, followed 4 days later by Pasteurella haemoly-
tica infection (Babiuk et al., 1984; Czarnieki et al., 1985). A
1-mg dose did not effectively reduce clinical scores
relative to the control placebo group. At the higher dose
rate, reductions in pyrexia, clinical signs, death, and lung
318 EA. Romnson

pathology were observed in this disease model. However,
as found with Hu-IFN above, virus excretion was not
reduced significantly, even in those animals protected
against challenge, suggesting that Bol FNa. may have more
of an immunomodulatory effect than a direct antiviral
effect in this model (Babiuk et a/., 1985). It is notable that
there was no difference in the level of intranasal interferon
secreted by control or interferon-treated animals, implying
that interferon treatment did not affect the production of
endogenous interferon. Of all the viruses implicated in the
initiation of 'shipping fever', BHV-1 is the least sensitive in
vitro to BoIFNa.and, since treatment of calves resulted in
reduced clinical signs of the disease induced by this virus,
it is probable that treatment with BoIFNa.may prove more
beneficial with respect to the other viruses involved in this
disease complex.
When the IFN inducer Poly I:C was given to calves, 1 mg
kg- 1 i.v., 3h prior to BHV-1 challenge, it did not prevent
infection, although the severity of respiratory disease and
pneumonic lesions in the lungs were reduced (Theil et aI.,

Table 2. Laboratory animal models for viruses of veterinary importance,and antivirals tested therein.

Laboratory animal Compounds

Virus model tested Activity Reference

Equine mice amantadine + Bryans et al. (1966)

influenza
EHV-1 hamsters idoxuridine Lieberman et et. (1972)
distamycin A Lieberman et et. (1972)
ribavirin + Sidwell et al. (1977)
Ara-T ++ Aswell et al. (1977)
Gentry et al. (1979)
5-Me-Ara-C ++ Aswell et al. (1977)
Gentry et al. (1979)
Ara-A +++ Aswell et al. (1977)
Gentry et al. (1979)
Ara-Hxrnp +++ Allen et al. (1975)
ACV +++ Rollinson and White
(1983)
OHPG ++++ Rollinson and White
(1983)
Polyl:C ++ Lieberman et al. (1972)
IFN exogenous ++ Lieberman et al. (1972)
Statolon +++(-) Lieberman et al. (1972)
NOV +++ Lieberman et al. (1972)
FIAC. FMAU,
FIAU + Rollinson (1987)
mice ACV + Field (1985)
PMEA ++ Field et al. (1991)
Field and Awan (1990)
HPMPA ++ H. J. Field et al.
(personal communication)
Field et al. (1992)
PCV ++ de la Fuente et al. (1992)
HPMPC Gibson et al. (1992)
WEEV mice ribavirin Sidwell et al. (1972)
Polyl:C ++(-) A. N. Ibrahim and S. Karatela
(pt>rsonal communication)
VEEV mice tilorone + Kuehne et al. (1977)
Rabies mice isoprinosine Glasgow and Galasso
(1972)
6-Azauridine Enright et al. (1971)
idoxuridine Enright et al. (1971)
NOV Atanasiu et al. (1970)
Polyl:C +(+) Nemes et al. (1969)
Janis and Habel (1972)
OHPA +++ Sodja and Holy (1980)
Sodja (1986)
l3-phenylserine Pons and Preston (1961)
rabbits NOV ++ Atanasiu et al. (1970)
Polyl:C ++ Janis and Habel (1972);
Fenje and Postic (1971)
hamsters NOV + Atanasiu et al. (1970)
 Antiviral chemistry in veterinary medicine 319

Canine
distemper ferrets isoprinosine Glasgow and Galasso
(1972)
SHV-1 rabbits HPA-23 P. P. Pastoret et al.
(personal communication)
Evrard et al. (1984)
Phosphonoformate Vindevogel et al. (1982)
P. P. Pastoret et al.
(personal communication)
Acyclovir + Thiry et al. (1983)
mice BVDU -(+) Field (1985)
Rollinson (1988)
acyclovir + Rollinson and White
(1983)
Field (1985)
DHPG ++ Rollinson and White
(1983)
Field (1985)
heparin +++ Aguilar-Setien et al.
(1983)
FIAC, FMAU,
FIAU + Rollinson (1987)
FMDV mice Polyl:C +++ Richmond and Hamilton
(1969)
guinea pig 6MFA + Lal et al. (1980)
BHV-1 rabbits BVDU Rollinson (1988)
RVFV mice ribavirin +++ Westover et al. (1981)
Jones et al. (1979)
Canonico et al. (1984)
Scrapie mice heparin Ehlers and Diringer (1984)
dextransulphates +H Ehlers and Diringer (1984)
RSV cotton rats ribavirin + Wyde et al. (1987)
Rotavirus mice N/A N/A Ward et al. (1990)

Abbreviations
EHV-1 Equine herpes virus type 1 (equine rhinopneumonitis, equine abortion)
WEEV Western equine encephalomyelitis virus
VEEV Venezuela equine encephalomyelitis virus
SHV-1 Suid herpes virus 1 (Aujeszky's disease, pseudorabies)
FMDV Foot and mouth disease virus
BHV-1 Bovid herpes virus type 1 (lnfectious bovine rhinotracheitis)
RVFV Rift valley fever virus
RSV Respiratory syncytial virus

1971).Another IFN inducer, ABPP, also showed activity in
reducing the duration and extent of clinical signs, virus
excretion, and lung lesions in BHV-1 challenged calves;
the drug was administered either 12 h prior to BHV-1
exposure or 6h post exposure, and given once daily (1 g
per calf) for 6 consecutive days (Hamdy and Stringfellow,
19aO).
In vitro experiments showed that levamisole consisten-
tly enhanced both macrophage and lymphocyte functions
with a resultant increase in o-tnterferon production
(Babiuk et al., 19a4). However, in experiments in cattle to
determine how far levamisole could be used to obviate the
stress-related immunosuppression associated with
shipping fever, variable results were obtained. In one case,
the levamisole was administered (6mg kg- 1) in combin-
ation with a live-attenuated BHV-1 vaccine. In normal
unstressed animals, levamisole administration at the time
of vaccination resulted in a decreased antibody and
cell-mediated response to BHV-1. However, if animals
were transported and then treated with levamisole, there
appeared to be an enhanced antibody response and
concurrent reduction in virus excretion. In another large
field trial, levamisole administration had no effect on
morbidity due to respiratory disease, but was associated
with improved daily weight gain and feed conversion.
The sugar analogues 2-deoxy-D-glucose (2-dG) and
glucosamine have been evaluated against two bovine
respiratory viruses. Daily injection of 2-dG (20mg kg- 1 Lv.)
had no protective or ameliorating effect against experi-
mental respiratory tract infection in calves caused by
BHV-1. However, ocular instillation of the drug markedly
reduced the severity of conjunctivitis and keratoconjuncti-
vitis, when given either at the time of infection or after
clinical signs developed (Mohanty et aI., 19aO). Thus,
topical 2-dG may have chemotherapeutic potential in
conjunctivitis in cattle caused by BHV-1. A similar dose
regimen, but at 10mg kg-1, was used to investigate the
effect of 2-dG against experimental bovine respiratory
320 E. A. Rollinson
syncytial virus infection in calves (Mohanty et al., 1981).
Respiratory tract disease due to this virus is usually less
severe than that caused by BHV-1. Although i.v, treatment
protected against the development of mild clinical signs of
respiratory disease, there was no effect on the gross and
histopathological changes produced by the virus in the
lungs. The drug was ineffective when administered after
the onset of clinical disease and there was no added
advantage in administering it intranasally at the time of
infection. Ribavirin treatment, on the other hand, when
given 3 days post RSV challenge (72mg i.v., Day 1
followed by 60 mg on Days 2 and 3), did lead to a reduction
in symptoms of disease, and there were no adverse
systemic effects of therapy (Bartzatt and Anderson, 1989).
Further studies on ribavirin treatment of cattle with
pneumonia (n = 14), diarrhoea (n = 10) or malignant
catarrhal fever (n = 1) were reported by V. Ya. Mozgiz et al.
(personal communication). Calves were treated orally at
5mg kg-1, 3-4 times daily, for 3-5 days. All treated
animals recovered and had better weight gains than the
controls, five of which died.
Gilliam and Field (1992) established that HPMPC is
active against the BHV-1 in tissue culture at a concentra-
tion of4 fL9 rnl". They then designed an experimenttotest
the efficacy of a single dose of HPMPC in experimentally
infected calves. Eleven calves, shown to be free from
BHV-1 by serological tests, were infected by means of
intranasal instillation. All untreated animals developed
clinical signs including fever and ocular and nasal dischar-
ges. High titres of virus were recovered from nasal and
ocular secretions. An injection of 20mg kg- 1 of HPMPC
given once on the day before, or day after virus inoculation
had a profound affect on clinical signs. The therapeutic
dose reduced virus shedding in all sites by several log10.
The development of antibody to the infecting Virus was
different in the treated animals compared to untreated
controls. It was of interest that the animals which had been
treated during the acute infection showed a reduced and
different pattern of virus shedding on reactivation. A
therapeutic dose of HPMPC was also able to modify the
pattern of virus reactivation in animals which had not been
treated during the initial infection. These findings are
particularly important since they demonstrate efficacy of a
single dose of the antiviral agent HPMPC against an alpha
herpesvirus in its natural host.
Malignant catarrhal fever virus (MCFV) is slightly sensi-
tive to acyclovir in vitro but no activity was demonstrable in
a rabbit disease model of MCF (N. Edington, personal
communication).
Bovine leukaemia virus was moderately sensitive to
Ribavirin in vitro (Sidwell and Smee, 1981), and to suramin,
HPA-23 and AZT (Reiner et al., 1989) while cyclophospha-
mide treatment of BLV-infected cattle was ineffective (Van
der Maaten, 1984). Suramin treatment of BLV-infected
sheep (20 mg kg- 1 per week from week 10 to week 16 post
infection) lead to a significant, but transient, dis-
appearance of P24 antigen and did not affect the titre of
anti-P24 or gp51 antibodies (Burkhardt and Ros, 1989;
Rosenthal et el., 1990).
Equine viruses
A small-scale trial by Bryans et al. in 1966 demonstrated
that oral treatment with amantadine (by intubation, twice
daily for 11 days, at 20mg kg- 1 dose- 1) SUbstantially
reduced equine influenza virus excretion in experimentally
infected horses. The authors suggest that (assuming
comparable activity existed for future antigenic variant
viruses) amantadine might be used to limit the spread of
disease caused by such variant influenza virus until such
time as an updated vaccine was licensed.
In a study of 439 clinical cases (Thein and Hechler;
1983), a radiation-inactivated preparation of avipoxvirus
(pind-Avi), an inducer of 'paraimmunity' in the horse, was
useful in preventing equine influenza and respiratory
disease in foals, but it was of no value in treating acute or
chronic respiratory disease in horses.
Provided that therapy is administered frequently, idox-
uridine and acyclovir have been used with success against
herpetic keratitis in horses (Matthews and Handscombe,
1983; Bedford, 1985; N. Irby, personal communication).
Although ACV was effective in preventing EHV-1 induced
mortality (from hepatitis) in Syrian hamsters (Rollinson and
White, 1983), preliminary investigations on the pharmaco-
kinetics of ACV in the horse (Rollinson, 1988) indicated
that it is unlikely to be a suitable antiviral for treatment of
equine rhinopneumonitis, because of short half-life and
poor absorption from the gut. A therapeutic effect could
possibly be achieved in the horse after dosing at 20 mg
kg- 1 i.v, every8h, but such a dose regimen is unlikely to be
acceptable in practice. Moreover, i.v, administration was
regularly followed by symptoms of colic, possibly caused
by crystalluria. Relatively low plasma levels were obtained
following oral dosing as a result of poor absorption. It
would appear that the pharmacokinetics of ACV in the
horse differ markedly from humans and other species.
When ACV was used to treat foals which had been
naturally infected in utero by EHV-1, there was no
response to therapy (5mg kg- 1 i.v. 2-3 times daily) (D.
Powell, personal communication). Of possibly much
greater potential is the ACV congener DHPG, which has
outstanding in vitro activity against EHV-1 ICso 0.06 fL9
mr' and in vivo in the hamster disease model (EDso 0.4 fL9
mr' day-l) (Rollinson and White, 1983). In a small
experimental study, four ponies received DHPG orally,
30 kg kg- 1, twice daily for 5 days beginning 5 h pre-infec-
tion. The height and duration of pyrexia in these ponies
was reduced compared with the untreated controls, as

was the level of virus shedding. The duration of virus
shedding appeared to be unaffected by treatment, as
were the serological responses of the ponies to infection
(E. A. Rollinson, unpublished observations). In a further
study to investigate the possible use of DHPG in treating
EHV-1 infected pregnant mares, it appeared that DHPG
did not cross the placenta in late gestation (P. Rossdale
and E. A. Rollinson, unpublished observations). Impor-
tantly, DHPG appeared to be free of the acute adverse
effects produced by ACV in the horse. Activity in vitro of
DHPG has also been reported for equine coital exanthema
(EHV-3, ICso 0.16 JLg mr') (Smith et aI., 1983).
Field and colleagues (Field and Awan 1990; H. J. Field et
al., personal communication; 1992) have reported on the
marked effects of HPMPA ([S]-9-[3-hydroxy-2-phos-
phonyl methoxypropyl] adenine) on the pathogenesis of
EHV-1 in a murine model, and more recently in horses
(Gibson et al., 1992). When treatment in mice was
commenced before infection, virus replication in the
respiratory tract was virtually eliminated, viraemia was
cleared and progression of clinical signs was reversed.
Effects of therapy were less marked-when treatment was
begun post-infection. PMEA was only marginally effective
in this murine model. The in vivo data reflected the in vitro
results, where HPMPA had an ICso of 0.1 JLg rnr', with
PMEA some 10-fold less active. The mode of action of
HPMPA differs from that of DHPG, in that it acts indepen-
dently of the virus encoded thymidine kinase, and TK-
mutants remain sensitive to HPMPA.
InnoVet is submitting a US licence application for its
immunostimulant IVET-629, in 1992, for treatment of
chronic equine respiratory diseases. IVET-629 exhibits
selective stimulation of B-Iymphocytes, which may have
some effect on resistance to reinfection (Anon, 1992a).
Potential problem of drug resistance
If antiviral drugs become available for general use, it is
probable that resistant viral strains will develop, as
bacterial strains have done to antibacterials. The methods
for evaluating resistance and the mechanisms of resist-
ance to antiviral agents are dealt With elsewhere (Field,
1983, 1988; Larder and Darby, 1984). Although it is well
known that drug resistance may be acquired by viruses in
Vitro, little is yet known of the significance of resistance in
the clinical situation. For example, mutants of FIVresistant
to AZT have been reported (Remington et aI., 1991). Initial
indications regarding one kind of resistance, herpes
simplex virus type 1 to ACV, are encouraging, in that some
resistant strains of HSV-1 (which manifest resistance by
virtue of being thymidine-kinase negative) tend to have
reduced virulence (Field, 1983). Similarly, when compar-
ing the pathogenicity for mice of various vaccine strains of
SHV-1, van Oirschot and Gielkens (1984)found that mice
Antiviral chemistry in veterinary medicine 321
were resistant only to the strain which did 'not induce
thymidine kinase in pig kidney cells, but were susceptible
to the TK+ strains. Ben-Poratt et al. (1984) have reported
that a TK- strain of SHV-1 was avirulent in swine.
Combination therapy may offer a means by which the
development of drug resistance can be reduced, by the
use of two drugs with different mechanisms of inhibition.
Reports on the combined effects of antiviral agents on
Viruses of veterinary importance are scant, excepting for
those on use of IFN and nucleoside analogues, reported
under feline leukaemia and FIV in Part 1.
Concluding remarks
The success of acyclovir (ZOVIRAX®) and zidovudine
(RETROVIR®) and the huge research and development
commitment throughout the human pharmaceutical com-
panies towards antiretroviral compounds is undoubtedly
improving the prospects for the availability of specific
antiviral compounds for veterinary use, especially for FeLV
and FIV. Non-specific immune modulators, with antiviral
activity are now nearing the market, e.g. InnoVet's IVET-
629 for the treatment of equine respiratory disease and
shipping fever in cattle. However, there still remains the
economic conundrum, of how far the high costs of
development and registration of specific veterinary antivi-
rals per se will be justified by subsequent financial return
from sales. The advent of antivirals with a relatively broad
spectrum of activity but low toxicity, such as HPMPA and
HPMPC, is encouraging in this respect. There is likely to be
continued use, in animals, of antivirals which are regis-
tered for human use only. Additionally, antiviral agents are
extremely useful as research tools per se, as opposed to
chemotherapeutic agents alone, and can be used
selectively to define and/or generate virus isolates with
particular profiles, for example. There are still many
obstacles to overcome in the practical use of veterinary
antivirals, especially that of prompt diagnosis to facilitate
early treatment. Further progress in the development of
diagnostic tools will be a prerequisite to successful
veterinary antiviral chemotherapy. Alternatively, it may be
possible to anticipate when viral infections may threaten
and to treat them strategically. Prophylactic treatment
may well be worthwhile, e.g. when animals are subjected
to stress situations, such as being transported, marketed,
mixed with other stock, racing or competing, etc., or are
likely to be exposed to infection for some other reason,
although suitable withdrawal periods would have to be
defined for competition horses, for example. Breeding
stock, particularly of horses, cattle, pig, and sheep, where
viruses are important causes of abortion and infertility, are
obvious targets for antiviral chemotherapy. The increase
in artificial insemination and embryo transfer, especially in
cattle, offers another possibility for the use of antivirals in
322 E. A. Rollinson
preventing the transmission of venereally associated viral
agents.
Antiviral chemotherapy and vaccination need not be
mutually exclusive, both approaches being used in certain
circumstances for the control of virus diseases, e.g.
vaccine breakdown, or where an animal is likely to suffer
adverse reactions to vaccination. Chemotherapy and
vaccination were proposed as a possible control strategy
for highly viruent influenza viruses in chickens, especially
under conditions where eradication is not a viable option
(Webster et al., 1985, 1986). Either measure alone did not
prevent development of the disease and mortality, but
simultaneous administration of an H5N2 vaccine and
amantadine protected birds from infection.
There is still much to be learned concerning the
pathogenesis of virus infections of domestic animals,
birds, and fish. Only by improving our understanding ofthe
many factors involved in the disease process and under-
taking concomitant studies on pharmacokinetics/pharm-
acodynamics will it become possible to design effective
chemotherapeutic regimens. Technology is advancing
regarding the targeting of drugs to the site of infection by
using prod rugs (Krenitsky et al., 1984), by using protein
carriers (Fiume et al., 1988), by modifying drugs to resist
metabolic degradation, by use of liposomes or polymers
to encapsulate/allow slow or pulse release (Canonico et
al., 1984; Kende et al., 1985; Koff and Fidler, 1985). These
advances in drug delivery will be of particular importance
in veterinary practice, since repeated dosing is not always
practicable or cost effective. In this context, the reported
efficacy of a single dose of the antiviral agent HPMPC
against BHV-1 infection in cattle is particularly exciting,
and suggests that it will be possible to overcome the
hurdle of practicable administration. Overall, specific
veterinary antiviral chemotherapy is having a continuing,
significant and rewarding role, now and in the future,
particularly for the retrovirus diseases of cats, and
herpesvirus infections of many domestic animals.
Acknowledgements
I am extremely grateful to Miss Diane Claydon for her efforts in
typing the manuscript, to Mrs Sue Adlern for obtaining references
and to David Rollinson for comments and support.
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