Characterization of the secretory glycoprotein 90K/LGALS3BP as an antiviral restriction factor
DFG Collaborative Research Centre 900: chronic infections: "Microbial Persistence and its Control"
After recognition of pathogen-associated molecular patterns (PAMPs) by infected cells, interferons are synthesized, secreted and bind the interferon receptor on neighboring cells to „alarm“ them from an upcoming virus invasion. Binding induces a signaling cascade that ultimately results in synthesis of several interferon-stimulated genes, so-called ISGs (“interferon-stimulated genes”). ISGs comprise many antiviral genes, including those encoding APOBEC3G, a cellular deaminase which hypermutates the viral genome, or Tetherin, which prevents release of mature virions from the producer cell´s surface. Another ISG is lgals3bp, which encodes for the cellular glycoprotein 90K. Previous work of our group demonstrated the antiviral potency of 90K against HIV. Specifically, 90K reduces the infectivity of newly assembled virions by interfering with the viral incorporation of HIV Envelope proteins (Lodermeyer et al., Retrovirology 2013). We are now focusing on the elucidation of the antiviral mechanism. Using truncated versions of 90K, we plan to define which domains/regions within 90K are essential and sufficient for its antiviral function. In parallel, 90K orthologs from non-human species, which share a high degree of homology with human 90K, but differ in their antiviral capability, are useful tools for the elucidation of the antiviral mechanism. Further, they shed light on the evolutionary conservation of 90K´s antiviral function. Finally, we test whether 90K acts antivirally against other enveloped viruses. The long-term perspective is to pave avenues towards a new antiviral treatment strategy.
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DFG - German Research Foundation