To confirm our previous findings through ATCV-1 intracranial injection into SOD1G93A-transgenic mice, including a second chlorovirus PBCV-1 type, and the assessment of viral effect on the onset and development of an ALS phenotype.

Infectious exposures contributing to MND include WNV, poliovirus, HIV, and cyanobacteria [1]. We have demonstrated that sera from ALS patients have significantly elevated IgG1 antibody levels to chlorovirus ATCV-1.  SOD1G93A-transgenic mice exposed at 5 weeks of age to ATCV-1 developed an accelerated onset and progression of MND [2]. As chloroviruses (CV) have shown to infect mammalian macrophages [3],  they may also function as initiators of neurodegeneration. ATCV-1 is one of several CV's encoding its own SOD1. An expanded SOD1 transgenic animal study utilizing additional CV types to assess their effects on the pathogenesis of ALS is in order.

Eight SOD1G93A-transgenic mice were injected intracranially at 5 weeks of age with 5 x 10⁸ infectious ATCV-1 or with PBCV-1 virus particles. Another ten SOD1G93A-transgenic mice were injected with an equal volume of saline and five C57Bl/6 non-transgenic mice were injected with PBCV-1.  These mice were daily monitored for development of motor dysfunction, including tail paralysis, hindlimb tucking, decreased righting reflex, and latency to fall in a hanging cage lid test. Following euthanization, neuropathological analysis of CNS tissue was performed, including  assessment of cellular inflammatory mediators of disease activity.

This study demonstrated a statistically significant acceleration of onset and progression of motor dysfunction in both ATCV-1 and PBCV-1 infected SOD1G93A-transgenic mice. Measures of pathologic inflammatory mediators were also performed and will subsequently be presented.

This study of chlorovirus infection has identified an accelerated rate of onset and progression of MND symptomatology within SOD1G93A-transgenic mice. These findings reproduce our earlier results that chloroviruses, ubiquitous in fresh water aquatic environments, appear to be involved in the pathogenesis of ALS.