Anti-viral effects of CGRP in mixed glial cells infected with LP-BM5 virus (VIR5P.1022)

Abstract

Abstract LP-BM5 retrovirus infection is an established murine model used to study HIV infection in humans due to that susceptible strains of mice (including C57BL/6(B6) mice) develop immunodeficiency syndrome (termed as MAIDS) following LP-BM5 infection. Previously, we observed that calcitonin gene related protein (CGRP), a neuropeptide produced primarily by sensory neurons, reduced LP-BM5 viral loads in infected mixed glial cells (primarily astrocytes and microglia). The mechanism through which CGRP decreases the viral loads is still not known. To elucidate the role of CGRP in glial LP-BM5 infection, we first determined that CGRP did not induce an increased cell death post-infection or directly decrease the viral infectivity. Then, we investigated whether CGRP could affect viral infectivity by enhancing the glycosylation of the cell receptor for viral attachment, murine cationic amino acid transporter 1 (mCAT-1). Our data indicate that blocking glycosylation by Tunicamycin did not affect CGRP’s anti-viral effects. Further, we tested the involvement of p38 MAPK pathway in CGRP-induced inhibitory effects. Preliminary experiment using a p38 inhibitor, SB203580, suggests a p38 mediated mechanism. Future studies will further elucidate the role of p38 and examine the role of other CGRP downstream pathways on LPBM5 infection.