Viruses may contribute to motor neuron disease (MND) or Amyotrophic Lateral Sclerosis (ALS) by inducing inflammatory cytokines. Chloroviruses (CVs) are large dsDNA viruses, located ubiquitously in fresh-water environments worldwide, and were recently shown to replicate in macrophages, inducing inflammatory cytokines. Interestingly, they also encode a functional Cu-Zn superoxide dismutase (SOD), involving several SOD1 variants, including G93A.

Sera from 17 ALS patients and 13 age-matched controls were evaluated for antibody directed against ATCV-1 CVs and for inflammatory cytokines, determining whether significant human exposures to chloroviruses in ALS exist.  To subsequently assess the influence of chloroviruses on the development of motor deterioration, ATCV-1, heat-killed ATCV-1, poly I:C, or saline were injected intracranially into both SOD1G93A-transgenic and C57Bl/6 wild-type mice at 5 weeks of age. Poly I:C was also injected as a control of innate anti-viral immune responses without infection.

Antibody to ATCV-1 was detected in serum samples from both ALS patients and healthy controls, but IgG1-type antibody was significantly higher in ALS serum. ATCV-1 infection of SOD1G93A transgenic mice significantly accelerated onset and progression of motor loss and mortality, when compared to saline-treated transgenics. By contrast, heat-killed ATCV-1 did not accelerate loss of motor function, while poly I:C was found to significantly delay mortality in transgenic ALS mice.  

These studies detected heightened IgG1 antibody response to ATCV-1 in ALS serum, and revealed that exposure to chlorovirus ATCV-1 significantly accelerates onset of ALS-like MND in a transgenic mouse model. These findings together suggest that infection with chloroviruses may play a role in the pathogenesis of ALS/MND, and that components of the innate antiviral immune response appear to have a beneficial effect on motor disease progression.