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Toward the understanding of DSG2 and CD46 interaction with HAdV-11 fiber, a super-complex analysis
Gregory Effantin1, Marc-André Hograindleur1, Daphna Fenel1
1Université Grenoble Alpes, CNRS, CEA, IBS , Grenoble, France.
Importance:
The main limitation of oncolytic vectors is neutralization by blood components, which prevents intratumoral administration to patients. Enadenotucirev, a chimeric HAdV-11p/HAdV-3 adenovirus identified by bio-selection, is a low seroprevalence vector active against a broad range of human carcinoma cell lines. At this stage, there's still some uncertainty about tropism and primary receptor utilization by HAdV-11. However, this information is very important, as it has a direct influence on the effectiveness of HAdV-11-based vectors. The aim of this work is to determine which of the two receptors, DSG2 and CD46, is involved in the attachment of the virus to the host, and what role they play in the early stages of infection.
Insights
This study investigates the HAdV-11 adenovirus receptor usage, focusing on DSG2 and CD46. Understanding these interactions is crucial for developing effective oncolytic adenovirus therapies against cancer.
Area of Science:
- Virology
- Oncology
- Molecular Biology
Background:
- Oncolytic viruses face neutralization by blood components, limiting intratumoral delivery.
- Enadenotucirev, a chimeric adenovirus (HAdV-11p/HAdV-3), shows broad activity against carcinoma cells and has low seroprevalence.
- HAdV-11 tropism and primary receptor utilization remain unclear, impacting vector efficacy.
Purpose of the Study:
- To identify the specific host cell receptors (DSG2 or CD46) utilized by HAdV-11 for viral attachment.
- To elucidate the role of these receptors in the early stages of HAdV-11 infection.
Main Methods:
- Bio-selection of chimeric adenovirus (Enadenotucirev).
- Investigation of HAdV-11 tropism and primary receptor utilization.
- Analysis of DSG2 and CD46 involvement in viral attachment and infection.
Main Results:
- Identification of the primary receptor(s) for HAdV-11 attachment.
- Characterization of the role of DSG2 and CD46 in HAdV-11 entry.
- Insights into the early infection mechanisms of HAdV-11.
Conclusions:
- Determining HAdV-11 receptor usage is critical for optimizing oncolytic adenovirus vector design.
- This research clarifies essential aspects of HAdV-11 tropism, paving the way for improved cancer therapies.
