Targeting insideout phosphatidylserine as a therapeutic strategy for viral diseases

Abstract

Targeting exposed anionic phospholipids on a spectrum of virus-infected cells can protect against lethal virus infections in vivo. Keywords phosphatidylserine; antiviral; therapeutic There is a pressing need for anti-viral agents that are effective against multiple classes of viruses. Broad specificity might be achieved by targeting phospholipids that are widely expressed on infected host cells or viral envelopes. We reasoned that events occurring during virus replication (e.g. cell activation or pre-apoptotic changes) would trigger the exposure of normally-intracellular anionic phospholipids on the outer surface of virus-infected cells. A chimeric antibody, bavituximab, was used to identify and target the exposed anionic phospholipids. Infection of cells with Pichinde virus (a model for Lassa fever virus, a potential bioterrorism agent) led to the exposure of anionic phospholipids. Bavituximab treatment cured overt disease in guinea pigs lethally infected with Pichinde virus. Direct clearance of infectious virus from the blood and antibody-dependent cellular cytotoxicity of virus-infected cells appeared to be the major anti-viral mechanisms. Combination therapy with bavituximab and ribavirin was more effective than either drug alone. Bavituximab also bound to cells infected with multiple other viruses and rescued mice with lethal murine cytomegalovirus infections. Targeting exposed anionic Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#term