Summary auto-generated
This study demonstrated that ovine pulmonary adenocarcinoma (OPA), a lung cancer caused by jaagsiekte sheep retrovirus (JSRV), can be successfully induced in lambs inoculated at 1, 3, and 6 months of age, not just in neonates. Scottish Blackface lambs in four age groups received intratracheal inoculation of JSRV-containing lung fluid. Clinical disease and pathologically confirmed OPA developed in 62-90% of older lambs, with incubation periods ranging from 92 to 209 days depending on age. Younger lambs (1 week old) developed disease faster (70-74 days) than older lambs. Importantly, JSRV viraemia was detectable in peripheral blood via PCR before clinical signs appeared in all age groups, occurring earlier in younger animals. The researchers developed a sensitive PCR assay targeting the JSRV U3 region to detect viral DNA in blood samples. Histopathological examination confirmed papillary adenocarcinoma of alveolar type II and Clara cells across all age groups. The age-dependent susceptibility likely reflects differences in target cell availability, as these lung cell types are more abundant in neonates and decline significantly during the first month of life. These findings enable improved investigation of OPA pathogenesis and vaccine development.
Key findings
- JSRV infection and OPA can be induced in 100% of lambs aged 1-6 months, with 62-90% developing clinical disease and 87-100% showing pathological lesions
- Incubation period increases significantly with age at inoculation, ranging from ~71 days in 1-week-old lambs to ~185 days in 3-month-old lambs
- JSRV viraemia is detectable in peripheral blood before clinical signs appear across all age groups, occurring earlier in younger animals and enabling preclinical diagnosis
- Age-dependent susceptibility likely reflects the availability of target cells (alveolar type II and Clara cells), which are proportionally more abundant in newborns and decline dramatically during the first month of life
- A sensitive PCR assay was developed to detect JSRV DNA in blood samples, enabling non-lethal monitoring of infection progression and potential vaccine efficacy studies
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Abstract
Ovine pulmonary adenocarcinoma (OPA) can be reproduced consistently in neonatal lambs by intratracheal injection of inocula containing jaagsiekte sheep retrovirus (JSRV). In this study, clinical disease, confirmed pathologically as OPA, was induced in a high proportion of lambs that had been inoculated intratracheally with infectious lung fluid at 1, 3 and 6 months of age. The incubation periods, however, were longer in these three age groups than in 1-week-old lambs that were used as controls. Viraemia was detected in all age groups before onset of clinical signs, but occurred later in older animals. These results suggest an age-dependent susceptibility to OPA that could be determined by the availability of JSRV target cells in the ovine lung. The feasibility of inducing OPA in older lambs and detecting JSRV viraemia in preclinical stages enables improved studies on the pathogenesis, assessment of vaccines, diagnosis and control of the disease.