Axonal degeneration as a self‐destructive defense mechanism against neurotropic virus infection

C57BL/Wld S (Wallerian degeneration slow mutant) mice are protected from axonal (Wallerian) degeneration by overexpression of a fusion protein (Wld S ). We tested whether delay of axonal degeneration in Wld S mice could be beneficial in mice infected with GDVII and DA strains of Theiler's murine encephalomyelitis virus (TMEV), which spread in the central nervous system (CNS) using axonal transport. We infected Wld S mice and their parent strain, C57BL/6 (B6) mice, with virulent GDVII virus. One week after GDVII virus infection, 97% of B6 mice died, while 36% of Wld S mice survived. LD 50 in B6 and Wld S mice were 1.1 and 23 plaque forming units, respectively. Wld S mice had neuronal death (apoptosis) and marked loss of MAP‐2 immunoreactivity, suggesting that apoptosis and dendritic pathology cannot be prevented by the Wld S gene. In contrast, infection with the less virulent DA virus resulted in limb paralysis only in Wld S mice with larger numbers of virus‐infected cells in the CNS. Although prolonged survival of axons in Wld S mice may be beneficial during GDVII virus infection, it could favor virus spread during DA virus infection. This suggests that axonal degeneration in B6 mice might be a beneficial mechanism that limits the spread of some neurotropic viruses. Supported by the University of Utah (Funding Incentive Seed Grant to IT) and the NIH (NS34497 to RSF).