Targeting inside-out phosphatidylserine as a therapeutic strategy for viral diseases
Targeting inside-out phosphatidylserine as a therapeutic strategy for viral diseases
Soares, M.M., et al. Nat. Med. 14, 633-40 (2008).
Speaker: Wei-Cheng Huang (黃偉誠) Time: 14:00~15:00, Mar. 25, 2009
Commentator: Dr. Yao Chang (張 堯博士) Place: Room 601
Abstract:
Phosphatidylserine (PS), an anionic phospholipid normally restricted to the inner leaflet of plasma membrane of resting cells. However, the exposure of PS occurs on the cell surface when cells undergo apoptopsis, cell injury, and cell activation. Previous studies showed that viral infections may trigger PS exposure by inducing apoptosis or activating PS transporters1. Based on these findings, the authors hypothesized that exposure of PS or other phospholipids was a common phenomenon of virus-infected cells and can further be used as a target for antiviral therapy. To test this hypothesis, the authors used an anti-PS antibody, bavituximab2 (ref.) to detect and target exposed PS after viral infections. They found that bavituximab not only recognized the exposed PS on the cells infected with Pichinde virus causing fatal hemorrhagic fever in guinea pigs, but also recognized the PS on the envelope of Pichinde virus. Next, the authors identify the therapeutic activity of bavituximab, the authors infected guinea pigs with Pichinde virus with a lethal dose and found that most infected guinea pigs treated with bavitaximab recovered from the fatal infection. Additionally, the combined treatment of bavituximab and ribavirin showed additive effect on reducing the mortality of infected guinea pigs. The protective effect of bavituximab was due to the clearance of infectious virus from the bloodstream and the induction of antibody-dependent cellular cytotoxicity. Besides, bavituximab also bound to the cells infected with a board spectrum of viruses and protected mice for lethal mouse cytomegalovirus infection. Taken together, the authors demonstrated that the PS on virus-infected cells and viruses themselves could be a potential effective target for the development of antiviral agents.
References:
1. Balasubramanian, K. & Schroit, A.J. Aminophospholipid asymmetry: A matter of life and death. Annu Rev Physiol 65, 701-734 (2003).
2. Ran, S., et al. Antitumor effects of a monoclonal antibody that binds anionic phospholipids on the surface of tumor blood vessels in mice. Clin Cancer Res 11, 1551-1562 (2005).