Ovine pulmonary adenocarcinoma (OPA) is a contagious lung cancer of sheep. OPA
is found in over 20 countries on the continents of Europe, Africa, America and Asia,
and in a wide variety of breeds. The tumour also has been diagnosed sporadically in
goats and wild moufflon. OPA is caused by an exogenous beta-retrovirus, jaagsiekte
sheep retrovirus (JSRV), which is different from the transcriptionally active
endogenous retroviral sequences present in the ovine genome. A unique feature of
OPA is the absence of a specific humoral immune response to JSRV, despite the
highly productive infection in the lungs and the disseminated lymphoid infection.
The absence of detectable antibodies has hampered the diagnosis and control of the
disease before the development of clinical signs. The disease can be reproduced
consistently in neonatal lambs by intra-tracheal injection of inocula containing
JSRV, but this experimental model was unsuitable for various purposes, such as the
assessment of potential vaccine preparations. In the present study, the clinical
disease was reproduced, pathologically confirmed as OPA, in a high proportion of
lambs inoculated intra-tracheally with infectious lung fluid at either one, three or six
months of age. The incubation periods, however, were found to be longer in the
older age groups than in one week old lambs. During the course of the experiment,
viraemia was detected consistently by PCR (JSRV U3 PCR). The persistent viraemia
and the delayed development of OPA in the older lambs paralleled epidemiological
observations in naturally affected flocks. The optimisation of the JSRV U3 PCR
represented an important breakthroughs for studies on the pathogenesis of this infection and for the diagnosis and control of the disease. JSRV U3 PCR was
employed for the first longitudinal survey for detecting JSRV infection in a flock
with natural history of OPA. Ewes and offspring were followed for a period of two
and half years and the JSRV U3 PCR test was repeated every 3-4 months. It was
shown that the flock was heavily infected with JSRV. The lambs from both negative
and positive mothers became JSRV positive as early as 20-30 days after birth. The
rate of infection of the ewes and of the lambs increased significantly after the first
test. JSRV incidence in the ewe population was higher in the period prior to lambing.
The results suggested that Texel breedline had a higher susceptibility to JSRV
infection and a higher probability ofremaining positive.
New envelope and capsid recombinant proteins were produced not only for
immunological assays but also for preliminary immunisation trials in sheep. The
present experiments have been able to overcome previous difficulties regarding
JSRV Env protein production.
In the present study IHC gave new insight about histogenesis and viral pathogenesis
of OPA. In fact SU Env protein was found widespread on the surface of tumour
cells. This finding proved that envelope protein is consistently produced suggesting
again a role in cell proliferation. These epidemiological and experimental
transmission data point to JSRV as a non-acute transforming retrovirus and raise
questions about the in vivo role of JSRV env gene in transformation.