Inhibition of type I interferon responses by adenovirus serotype-dependent Gas6 binding Journal Article


Authors: Nidetz, N. F.; Gallagher, T. M.; Wiethoff, C. M.
Article Title: Inhibition of type I interferon responses by adenovirus serotype-dependent Gas6 binding
Abstract: The clinical use of many adenovirus vaccine vectors (AdVs) is limited by the presence of pre-existing antibodies in human populations, which prevent common AdVs from transducing cells and expressing immunogenic gene products. Rare serotype AdVs, such as HAdV-28D can bypass pre-existing immunity. However, rare AdVs stimulate high-levels of type I interferon (IFN), which suppresses antigenic gene expression and therefore limits immunogenicity. Recent studies identified Gas6 as a factor that connects enveloped viruses to host-cell receptor tyrosine kinases, in turn generating signaling cascades that antagonize type I IFN responses. We discovered that Gas6 bound to the fiber proteins of common AdV serotypes, such as HAdV-5C, with a higher affinity than rare HAd-28D fibers. AdV-associated Gas6 suppressed IFN production by common AdVs and enhanced long-term expression of AdV encoded genes. We hypothesize that rare AdV serotypes might be engineered to include Gas6 binding motifs, thereby generating novel vectors that are more effective.
Keywords: Innate immunity; Adenovirus; gene therapy; Gas6; TAM receptors; Type I interferons; Vaccine vectors
Journal Title: Virology
Volume: 515
ISSN: 1096-0341; 0042-6822
Publisher: Elsevier Inc  
Journal Place: United States
Date Published: 2018
Start Page: 150
End Page: 157
Language: eng
DOI/URL:
Notes: LR: 20180416; CI: Copyright (c) 2017; JID: 0110674; OTO: NOTNLM; 2017/10/27 00:00 [received]; 2017/12/14 00:00 [revised]; 2017/12/15 00:00 [accepted]; 2017/12/31 06:00 [pubmed]; 2017/12/31 06:00 [medline]; 2017/12/31 06:00 [entrez]; ppublish