Sheep retrovirus structural protein induces lung tumours

Area of Science:

• Veterinary Medicine
• Oncology
• Virology

Background:

• Jaagsiekte sheep retrovirus (JSRV) causes contagious lung cancer in sheep and goats, impacting animal health and economies.
• Species-specific differences in the virus entry receptor, hyaluronidase 2 (Hyal2), partially limit JSRV's host range.
• Sheep's immunotolerance to JSRV, due to endogenous retroviruses, may facilitate oncogenesis.

Purpose of the Study:

• To investigate the oncogenic potential of the JSRV envelope (Env) protein in vivo.
• To determine the role of the virus entry receptor (Hyal2) in JSRV-induced tumorigenesis.
• To assess the impact of host immunity on JSRV-driven tumor development.

Main Methods:

• Utilized a replication-incompetent adeno-associated virus vector to express JSRV Env protein in mouse lungs.
• Compared tumor development in immunocompetent and immunodeficient mouse models.
• Evaluated the necessity of Env-Hyal2 interaction for tumorigenesis.

Main Results:

• Expression of JSRV Env protein alone in mouse lungs induced tumors with bronchiolo-alveolar localization, mimicking sheep disease.
• Lethal disease occurred in immunodeficient mice, while tumor development was significantly inhibited in immunocompetent mice.
• The interaction between the JSRV Env protein and the Hyal2 receptor was not required for tumor formation.

Conclusions:

• The JSRV Env protein is a rare example of an oncogenic viral structural protein.
• Immune recognition of the JSRV Env protein is crucial for protection against JSRV-induced tumorigenesis.
• Targeting viral Env protein interaction with host receptors is not essential for preventing JSRV-related lung cancer.