It is known that some viruses make use of the microtubules and/or the actin cytoskeleton for axonal transport (30Y32). Our studies have shown that a major mechanism of both retrograde and anterograde axonal transport of neurovirulent MHV is mediated by spike protein and further experiments will focus on identifying the molecular mechanisms by which the DM virus interacts with the axonal transport system and whether specific interventions targeting the transport system can delay or prevent the DM strain-induced axonal loss and demyelination. Analyzing the underlying principles of MHV axonal transport will be helpful in the design of viral vectors to be used in research, in human gene therapy, and in the identification of new antiviral therapies. Such therapies may also have the potential to prevent CNS demyelinating diseases that might be triggered initially by viral infection.  Non-Apical Membrane Antigen 1 (AMA1) IgGs from Malian Children Interfere with Functional Activity of AMA1 IgGs as Judged by Growth Inhibition Assay BACKGROUND: Apical membrane antigen 1 (AMA1) is one of the best-studied blood-stage malaria vaccine candidates. When an AMA1 vaccine was tested in a malaria naïve population, it induced functionally active antibodies judged by Growth Inhibition Assay (GIA). However, the same vaccine failed to induce higher growth-inhibitory activity in adults living in a malaria endemic area. Vaccination did induce functionally active antibodies in malaria-exposed children with less than 20% inhibition in GIA at baseline, but not in children with more than that level of baseline inhibition. METHODS: Total IgGs were purified from plasmas collected from the pediatric trial before and after immunization and pools of total IgGs were made. Another set of total IgGs was purified from U.S. adults immunized with AMA1 (US-total IgG). From these total IgGs, AMA1-specific and non-AMA1 IgGs were affinity purified and the functional activity of these IgGs was evaluated by GIA. Competition ELISA was performed with the U.S.-total IgG and non-AMA1 IgGs from malaria-exposed children. RESULTS: AMA1-specific IgGs from malaria-exposed children and U.S. vaccinees showed similar growth-inhibitory activity at the same concentrations. When mixed with U.S.-total IgG, non-AMA1 IgGs from children showed an interference effect in GIA. Interestingly, the interference effect was higher with non-AMA1 IgGs from higher titer pools. The non-AMA1 IgGs did not compete with anti-AMA1 antibody in U.S.-total IgG in the competition ELISA. CONCLUSION: Children living in a malaria endemic area have a fraction of IgGs that interferes with the biological activity of anti-AMA1 antibody as judged by GIA. While the mechanism of interference is not resolved in this study, these results suggest it is not caused by direct competition between non-AMA1 IgG and AMA1 protein. This study indicates that anti-malaria IgGs induced by natural exposure may interfere with the biological effect of antibody induced by an AMA1-based vaccine in the target population. WHO estimates there were 243 million malaria cases and 0.9 million deaths in 2008; the vast majority of deaths occurred in African children less than 5-years old due to Plasmodium falciparum, which is the most virulent species of human malaria [1] . While the protective mechanisms remain to be elucidated, a passive transfer study has shown the importance of gamma-globulin against bloodstages of P. falciparum [2] . To control and eventually eradicate malaria, an effective vaccine is considered to be needed, in addition to the existing tools, such as drugs, insecticides, etc. [3] .