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Comprehensive analysis of host cell response to human adenovirus type 26 infection
Category
Projekti Hrvatske zaklade za znanost
Total cost
199.955,00
EUR
Start date
Dec 5th 2025
End date
Dec 4th 2028
Status
Active

Adenovirus (AdV) based vectors are currently leading vectors used in gene therapy clinical trials, namely cancer treatment and vaccination. Low seroprevalent human adenovirus type 26 (HAdV-D26) emerged as a candidate for vaccine vector development and very recently HAdV-D26 based vaccines against Ebola and COVID-19 received marketing authorization from European Union. While HAdV-D26 immunogenicity in vivo is rather well described questions regarding basic biology of HAdV-D26 are still opened. Based on our previous data, namely the fact that HAdV-D26 co-localizes with avß3 integrin and when uses avß3 integrin as a receptor it enters the cells through caveolae, as well as preliminary different pattern of tyrosine phosphorylation observed between cells differing in avß3 integrin expression infected with HAdV-D26, we assume that HAdV-D26, due to binding to avß3 integrin and engaging in different cell entry pathway induces different profile of host response. Since host signalling and response induced by AdV vector limit and influence performance of vector itself, integrative studies assessing the host response following HAdV-D26 infection are highly warranted. Thus, the overall goal of AdenoHost is to address clear gap in the regulatory landscape of host signalling induced by HAdV-D26 infection of epithelial cells in the context of the avß3 integrin usage as HAdV-D26 receptor. This will be achieved through transcriptomic, proteomic and phosphoproteomic profiling of mock and HAdV-D26 infected epithelial cells with avß3 integrin increased expression. We expect to obtain comprehensive integrative analysis of biologically significant changes in HAdV-D26 infected epithelial cells and detailed understanding of HAdV-D26 induced host signalling after engaging avß3 integrin, new knowledge that will be valuable for further improvement of HAdV-D26-based vectors for gene transfer and vaccination, and virology in general.

Laboratory for Cell Biology and Signalling