Citations 3
Ex Vivo and In Vivo CD46 Receptor Utilization by Species D Human Adenovirus Serotype 26 (HAdV26)
Hemsath, Jack R. , Liaci, A. Manuel , Rubin, Jeffrey D. , Parrett, Brian J. , Lu, Shao‐Chia , Turner, Mallory A., Chen, Christopher Y. , Cupelli, Karolina, Reddy, Vijay , Stehle, Thilo , Liszewski, M. Kathryn , Atkinson, John P. , Barry, Michael A. , Stehle, Thilo , Barry, Michael A , Nguyen, Tien Anh
Journal of Virology | November 17, 2021 | Volume: 96 | Issue: 3 | Pages: No page available
The human species D Ad26 is being investigated as a low-seroprevalence vector for oncolytic virotherapy and gene-based vaccination against HIV-1 and SARS-CoV-2. However, there is debate in the literature about its tropism and receptor utilization, which directly influence its efficiency for certain applications. This work was aimed at determining which receptor(s) this virus uses for infection and its role in virus biology, vaccine efficacy, and, importantly, vaccine safety.
Myosin-1E interacts with FAK proline-rich region 1 to induce fibronectin-type matrix
Heim, Joel B. , Squirewell, Edwin J., Neu, Ancilla, Zocher, Georg , Sominidi‐Damodaran, Sindhuja , Wyles, Saranya P. , Nikolova, Ekaterina , Behrendt, Nille, Saunte, Ditte Marie Lindhardt , Lock‐Andersen, Jørgen, Gaonkar, Krutika S. , Yan, Huihuang , Deursen, Jan van, Sprangers, Remco , Stehle, Thilo , Böttcher, Ralph T. , Lee, Jeong‐Heon , Ördög, Tamás , Meves, Alexander , van Deursen, Jan, Meves, Alexander , Sarkaria, Jann N. , Krendel, Mira , Lee, Jeong-Heon , Heim, Joel B
Proceedings of the National Academy of Sciences | March 27, 2017 | Volume: 114 | Issue: 15 | Pages: 3933-3938
Significance Focal adhesion kinase (FAK) is an intensely studied protein involved in many medically relevant biological processes, including cancer. Despite the large interest in FAK, a promising strategy to target FAK therapeutically is elusive. Here, we show that a region within the FAK protein that contains autophosphorylation site tyrosine (Y) 397 is essential for FAK activity in vivo. Myosin-1E (MYO1E), an actin-dependent molecular motor protein, directly interacts with FAK to induce Y397 autophosphorylation, which, in turn, causes changes in gene expression commonly observed in aggressive cancer. Our findings are significant because they further delineate FAK function in vivo and identify the MYO1E–FAK interaction as a possible Achilles’ heel for cancer.
In Vitro and In Vivo Properties of Adenovirus Vectors with Increased Affinity to CD46
Wang, Hongjie , Liu, Ying , Li, Zong-Yi, Tuve, Sebastian, Stone, Daniel , Kalyushniy, Oleksandr, Shayakhmetov, Dmitry M. , Verlinde, Christophe L. M. J. , Stehle, Thilo , McVey, John H. , Baker, Andrew H. , Peng, Kah-Whye , Roffler, Steve R. , Lieber, André , Baker, Andrew H
Journal of Virology | August 28, 2008 | Volume: 82 | Issue: 21 | Pages: 10567-10579
ABSTRACT Gene transfer vectors containing adenovirus (Ad) serotype 35 (Ad35) fibers have shown promise for cancer and stem cell gene therapy. In this study, we attempted to improve the in vitro and in vivo infection properties of these vectors by increasing their affinity to the Ad35 fiber receptor CD46. We constructed Ad vectors containing either the wild-type Ad35 fiber knob (Ad5/35) or Ad35 knob mutants with 4-fold- and 60-fold-higher affinity to CD46 (Ad5/35+ and Ad5/35++, respectively). In in vitro studies with cell lines, the higher affinities of Ad5/35+ and Ad5/35++ to CD46 did not translate into correspondingly higher transduction efficiencies, regardless of the CD46 receptor density present on cells. However, in vivo, in a mouse model with preestablished CD46 high liver metastases, intravenous injection of Ad5/35++ resulted in more-efficient tumor cell transduction. We conclude that Ad5/35 vectors with increased affinity to CD46 have an advantage in competing with non-CD46-mediated sequestration of vector particles after intravenous injection.