Inflammatory and anti-viral responses of macrophages to viruses or their molecular components. We have investigated the activation of IRF3 in the antiviral response. Presently we are focusing on the response of macrophages to Chlorovirus ATCV-1, and other chloroviruses. We have found that these viruses infect and replicate in mouse and human macrophages of the M1 phenotype and primarily induce inflammatory responses from these macrophages during these responses. Our recent findings have shown that ATCV-1 is part of the human oropharyngeal microbiome and most humans have antibodies to ATCV-1 and its major capsid glycoprotein.  Interestingly, people with Amyotrophic Lateral Sclerosis have elevated levels of ATCV-1 antibody of the IgG1 subclass in serum and cerebral spinal fluid compared with healthy controls. To investigate the significance of these findings we injected intracranially ATCV-1 into the transgenic mouse model of ALS, ie. the SOD1G93A mouse. This triggered neuroinflammation.  Normally, these mice succumb to ALS-like symptoms in 180 days after birth. When we injected the transgenic mice with ATCV-1 the mice had a significantly early development of ALS-like symptoms. This suggests that the neuroinflammatory response triggered by ATCV-1 in these mice accelerated the development of ALS-like symptoms.  The present research will focus on the molecular trigger of ATCV-1 that induces inflammatory response from macrophage, which may be blocked therapeutically to prevent or slow the tragic outcome of ALS in humans.