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. |
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: |
S0042-6822(17)30421-X |
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 |