Interferon-induced transmembrane protein 3 (IFITM3) and its antiviral activity.

Infections caused by enveloped viruses require fusion with cellular membranes for viral genome entry. Viral entry occurs following an interaction of viral and cellular membranes allowing the formation of fusion pores, by which the virus accesses the cytoplasm. Here, we focus on interferon-induced transmembrane protein 3 (IFITM3) and its antiviral activity. IFITM3 is predicted to block or stall viral fusion at an intermediate state, causing viral propagation to fail. After introducing IFITM3, we describe the generalized lipid membrane fusion pathway and how it can be stalled, particularly with respect to IFITM3, and current questions regarding IFITM3's topology, with specific emphasis on IFITM3's amphipathic α-helix (AAH) 59V-68M, which is necessary for the antiviral activity. We report new hydrophobicity and hydrophobic moment calculations for this peptide and a variety of active site peptides from known membrane-remodeling proteins. Finally, we discuss the effects of posttranslational modifications and localization, how IFITM3's AAH may block viral fusion, and possible ramifications of membrane composition.

Adsorption and photodynamic efficiency of meso-tetrakis(p-sulfonatophenyl)porphyrin on the surface of bilayer lipid membranes.

The adsorption and photodynamic efficiency of 5,10,15,20-tetrakis(p-sulfonatophenyl)porphyrin (H2TPPS4) on bilayer lipid membranes (BLM) have been studied. The adsorption of H2TPPS4 on BLM leads to rising of the potential drop on the membrane/water interface which has been detected either by the intramembrane field compensation (IFC) method, or as ζ-potential of liposomes measured by the dynamic light scattering method. The dependence of this potential on the concentration of H2TPPS4 and KCl in the solution can be described in the frame of Gouy-Chapman model of diffuse double layer assuming that the molecules of H2TPPS4 adsorb on the surface of BLM as an anions with four charged groups. The potential disappeared when the pH of solution decreased from 6 to 3 allowing the conclusion that the protonated forms of H2TPPS4 can not adsorb on the BLM probably due to change of conformation or aggregation of the molecules. The photodynamic efficiency of H2TPPS4 was evaluated by measuring the rate of damage of the targets - molecules of styryl dye (di-4-ANEPPS) by singlet oxygen generated under illumination on the surface of BLM. This rate was proportional to the surface density of H2TPPS4 molecules on the membrane which was determined from the change of surface charge of the membrane due to adsorption of the H2TPPS4. These results indicate that the di-4-ANEPPS molecules are damaged by singlet oxygen generated by monomers of H2TPPS4 molecules adsorbed on the membrane. The rate of oxidation of di-4-ANEPPS molecules adsorbed on the same (cis) side of the membrane together with the H2TPPS4 molecules was either the same or higher than that when di-4-ANEPPS molecules were adsorbed on opposite (trans) side. It indicates that the quenching of singlet oxygen by the di-4-ANEPPS molecules at cis side of the membrane was negligible, in contrast to our earlier study when singlet oxygen was generated by aluminum(III) phthalocyanines with one or two peripheral sulfo groups. The difference between these phthalocyanines and H2TPPS4 was explained by their different adsorption depth in the membrane.