A dose-effect relationship for deltaretrovirus-dependent leukemogenesis in sheep

Area of Science:

• Veterinary Medicine
• Oncology
• Virology

Background:

• Retrovirus infections cause tumors with variable latency periods.
• Deltaretroviruses, like BLV, typically induce hematological malignancies in a small fraction of infected individuals after long latency.

Purpose of the Study:

• To investigate the factors influencing deltaretrovirus-induced leukemogenesis.
• To determine the role of bovine leukemia virus (BLV) replication levels in malignancy development in sheep.

Main Methods:

• Experimental infection of sheep with either leukemogenic or attenuated BLV molecular clones.
• Prospective monitoring of viral replication, reverse transcription (RT) levels, infected cell clonal expansion, and circulating proviruses for 8 months.

Main Results:

• Malignancy development in BLV-infected sheep was directly dependent on the level of BLV replication.
• Leukemogenic BLV clones showed significantly higher RT levels, infected cell expansion, and proviral mutations compared to attenuated clones.
• Both virus types induced parallel fluctuations in host lymphoid cells, viral loads, and infected cell proliferation, indicating quantitative differences.

Conclusions:

• Deltaretrovirus-induced leukemogenesis in sheep is a multi-step process.
• The amount of horizontally and vertically transmitted BLV is critical for disease progression over time.