Endogenous Ecotropic Murine Leukemia Virus Promotes Prion Pathogenesis in Senescence-accelerated Mice

Area of Science:

• Neuroscience
• Virology
• Gerontology

Background:

• Senescence-accelerated prone mice (SAMP) strains show age-related cognitive decline.
• SAMP strains harbor high levels of endogenous ecotropic murine leukemia virus (E-MuLV), unlike resistant SAMR1 mice.
• Retroviruses, including MuLV, are linked to accelerated prion disease pathogenesis.

Purpose of the Study:

• To investigate the role of endogenous E-MuLV in prion disease progression.
• To compare prion disease progression in E-MuLV-carrying SAMP10 mice versus E-MuLV-low SAMR1 mice.

Main Methods:

• Infection of SAMP10 and SAMR1 mice with the 22L scrapie strain via intracerebral and intraperitoneal routes.
• Assessment of survival times, PrPSc accumulation, and vacuolation.
• Treatment of infected cerebellar slice cultures from SAMP10 mice with zidovudine.

Main Results:

• SAMP10 mice exhibited significantly shorter survival times post-scrapie infection compared to SAMR1 mice.
• Earlier and more pronounced PrPSc accumulation and vacuolation were observed in SAMP10 mice.
• Zidovudine treatment reduced PrPSc accumulation in SAMP10 cerebellar slice cultures.

Conclusions:

• Endogenous E-MuLV contributes to accelerated prion pathogenesis.
• E-MuLV promotes early and elevated PrPSc accumulation, shortening survival.
• Targeting retroviral activity may be a strategy to mitigate prion disease progression.