Summary
Myxomatosis is an emergent disease in Iberian hare, having been
considered a rabbit disease for decades. Genome sequencing of the
strains obtained from affected Iberian hares showed to be distinct from
the classical strains that circulated in rabbits since the virus
introduction in Europe, in 1952. The main genomic difference concerns
the presence of an additional 2.8Kb region disrupting the M009L gene and
adding a set of genes with homology to the MYXV genes M060R, M061, M064
and M065R originated in poxviruses. After the emergence of this
recombinant virus (MYXV-Tol, ha-MYXV ), in the summer of 2019, recombinnat MYXV
was not detected in rabbit surveys suggesting apparent species
segregation with the MYXV classic strains persistently circulating in
rabbits.
Recently, a group of six unvaccinated European rabbits
(Oryctolagus cuniculus cuniculus ) from a backyard rabbitry in the
South Portugal, developed signs of myxomatosis (anorexia, dyspnoea,
oedema of eyelids, head, ears, external genitals and anus, and skin
myxomas in the base of the ears), five of them dying within 24-48 hours
of symptoms onset. Molecular analysis revealed that only the recombinant
myxoma virus was present.
This is the first documented report of a recombinant myxomatosis virus
in farm rabbits associated with high mortality, which
aggravates the concern for the future of the Iberian hare and wild
rabbits and the safety of the rabbit industry against which the existing
vaccines may not be fully protective.
Keywords: European rabbit, Oryctolagus cuniculus
cuniculus , rabbit farming, Recombinant myxoma virus, ha-MYXV, MYXV-Tol,
Myxomatosis, Myxoma virus
Introduction
Myxoma virus (MYXV) is a Leporipoxvirus from the Poxviridae family that
causes an infectious, often fatal, systemic disease in the European
rabbit called myxomatosis. The virus is a dsDNA that replicates in
cytoplasm (Murphy et al., 1995). After the virus introducing in France,
in 1952, MYXV spread throughout all Europe, with mortalities rates as
high as 90% (Fenner and Ratcliffe, 1965). Over the years, the virulence
of the strains decreased significantly due to increase of genetic
resistance by the host, development of immunity and natural selection of
less virulent strains (Fenner and Fantini, 1999; Kerr, 2012). Nowadays,
the disease persists and is considered one of the main reasons behind
the fragile conservation status (danger of extinction) of the European
rabbit (Duarte et al., 2018; Villafuerte and Delibes-Mateos, 2019; C. L.
Carvalho et al., 2020).
The development and production of heterologous and homologous vaccines
against myxomatosis for rabbits, proved to confer seroconversion in
almost 100% of rabbits (Hipra, 2003), and, along with the application
of biosafety measures, allow to control the disease in the industrial
rabbit farming and small rabbitries, contrarily to wild life.
During almost seven decades, myxomatosis has been rarely reported in
European brown hares (Collins, 1955; Wibbelt and Frolich, 2005), never
in Iberian hare, being considered a rabbit disease. However, in late
2018, a natural recombinant MYXV (ha-MYXV) emerged in Iberian hare,
leading to the first epidemic outbreaks in this species, throughout
Portugal and Spain (Bocanegra et al., 2019; C. L. Carvalho et al.,
2020). The change in host tropism was attributed to a genomic
modification comprising a 2.8kb insertion containing genes with homology
to the M060R, M061R, M064 and M065R genes of MYXV, which are located
around position 60Kb in the genome. The insert disrupted the M009L gene
(Dalton et al., 2019; Pinto et al., 2019) located around position 12Kb
in the MYXV genome, which became divided in two smaller ORFs.
To date, no cases of mortality in European rabbit due to this
recombinant virus have been documented, although cases of myxomatosis in
wild and domestic rabbits continue to be monitored and genotyped in
Portugal, under the scope of a national surveillance program (+Coelho
Project, dispatch 4575, 31 may 2017, MAFDR).
Here we report a case of high mortality (≈83%) in a small backyard
rabbitry. Genotyping confirmed the unique presence of a recombinant
virus, similar to the ha-MYXV identified in Iberian hares. None of the
rabbits was vaccinated impeding any inference on the degree of
protection conferred by commercial vaccines against the recombinant MYXV. However,
the confirmation that recombinat MYXV induces severe disease in rabbits, raises
new concerns for the wild and domestic leporid species, emphasizing the
need of continuous monitoring and genomic characterization of viruses
circulating in these species in the Iberia.