The Soluble Serum Protein Gas6 Bridges Virion Envelope Phosphatidylserine to the TAM Receptor Tyrosine Kinase Axl to Mediate Viral Entry

Kouki Morizono,et al., (2011) .Cell Host & Microbe. 9, 286–298

Speaker: Pei- Huan Lee (李佩寰)                                         Time: 13:10-14:00

Commentator: Hsiao-Sheng Liu Ph.D. (劉校生老師)         Place: Room 601

Abstract

The first step of viral infection is binding to its specific cell surface receptors. Viruses can use multiple strategies to facilitate binding to target cells. In this study, the authors discovered that enveloped viruses use a soluble protein in fatal calf serum (FCS) to facilitate viral entry. First, they found that cells preincubated with FCS increases transduction efficiencies of pseudotyped lentiviral vectors of enveloped viruses. Then, they further demonstrated that bProtein S in FCS and its human homologs (Gas6) efficiently bridge the virus to cells. It is known that hGas6 have two ligand –binding region. The N-terminal domain can bind to Phosphatidylserine (PtdSer) on apoptotic cells, while the C-terminal region binds to TAM receptor on phagocytes .This binding activates phagocytosis of dead cells by phagocytes. Here, the authors show that the N-terminal domain of Gas 6 binds to PtdSer on viral envelope and C-terminal region binds to Axl, which is one of TAM receptors on many cell types. Therefore, virus entry can be mediated by the same mechanism that was used for recognition of dead cells. Finally, the authors demonstrated that not only lentivirus vectors but vaccinia virus vectors can utilize the same apoptotic mimicry entry pathway via Gas6. In conclusion, this study identifies a Gas6-mediated entry mechanism which provides an alternative pathway for viral entry.

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