Human SOD1G93A influences the response of macrophages to chloroviruses or the major glycoproteins of chloroviruses.

Compared with PBCV-1 chlorovirus, ATCV-1 chlorovirus accelerates the onset of motor neuron disease in ALS model SOD1G93A mice and induces an ALS-associated inflammatory cytokine response from macrophages that is composed of high levels of Nitric oxide (NO) and IL-6.

We developed murine RAW264.7 macrophage cell lines that express human wtSOD1 or SOD1G93A. We isolated the major glycoproteins (gp) from chloroviruses PBCV-1, ATCV-1, OSy-NE5, and variants of PBCV-1 and then stimulated RAW cells with each. Because the protein IRF3 drives ISRE activity and along with ERK MAPKs induce innate anti-viral immune responses, we stimulated wtRAW cells and IRF3KO RAW cells with ATCV-1gp and P1L6gp in the presence or absence of the ERK MAPK inhibitor, U0126.

The results show that SOD1G93A in macrophages responding to certain chlorovirus glycoproteins enhances production of inflammatory factors associated with development of ALS. Moreover, IRF3 and ERK MAP kinases likely regulate the responses of macrophages to those chlorovirus glycoproteins.