Human immunodeficiency virus-1/simian immunodeficiency virus infection induces opening of pannexin-1 channels resulting in neuronal synaptic compromise: A novel therapeutic opportunity to prevent NeuroHIV.

In healthy conditions, pannexin-1 (Panx-1) channels are in a close state, but in several pathological conditions, including HIV and NeuroHIV, the channel becomes open. However, the mechanism or contribution of Panx-1 channels to the Human Immunodeficiency Virus-1 (HIV) pathogenesis and NeuroHIV are unknown. To determine the contribution of Panx-1 channels to the pathogenesis of NeuroHIV, we used a well-established model of Simian Immunodeficiency Virus (SIV) infection in macaques (Macaca mulatta) in the presence of and absence of a Panx-1 blocker to later examine the synaptic/axonal compromise induced for the virus. Using Golgi's staining, we demonstrated that SIV infection compromised synaptic and axonal structures, especially in the white matter. Blocking Panx-1 channels after SIV infection prevented the synaptic and axonal compromise induced by the virus, especially by maintaining the more complex synapses. Our data demonstrated that targeting Panx-1 channels can prevent and maybe revert brain synaptic compromise induced by SIV infection.