What is the clinical evidence from this study?

Intervention: Site-directed mutagenesis of the IG1 region. Primary outcome: Ad5 binding and CVB attachment.

What question did this study set out to answer?

To determine the tissue distribution of the coxsackievirus and adenovirus receptor during development and characterize the structural domains required for adenovirus and coxsackievirus binding.

February 1, 2000Experimental Cell ResearchOpen Access

Expression of the Adenovirus Receptor and Its Interaction with the Fiber Knob

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Key result

IG1 region mutagenesis completely inhibits Ad5 binding without affecting CVB attachment, revealing non-overlapping receptor interactions.

Population

Rodent models (embryonic and adult) and cell models for site-directed mutagenesis

Design

Preclinical

Authors

RTRichard P. TomkoNYU Langone Health CJClas B. JohanssonKarolinska University Hospital MTMaxim TotrovMolsoft (United States)

Discussion

Member takes

Implication

Remains preclinical in rodent models; leaves open whether IG1 mutagenesis can selectively block adenovirus without affecting coxsackievirus in humans.

Key Points

To determine the tissue distribution of the coxsackievirus and adenovirus receptor during development and characterize the structural domains required for adenovirus and coxsackievirus binding.
Assessed receptor tissue distribution in developing and adult rodents using immunohistochemistry.
Generated targeted mutations in the receptor's IG1 domain based on computer structural modeling to measure adenovirus 5 and coxsackievirus B attachment.
Evaluated domain-specific antibody interference against the IG2 region to identify coxsackievirus binding regions.
Receptor expression was widespread in the central and peripheral nervous systems and epithelial cells during embryogenesis, becoming primarily restricted to epithelial cells in adults.
A double amino acid substitution in the IG1 three-stranded antiparallel beta sheet completely abolished adenovirus 5 binding without impairing coxsackievirus attachment.
An antibody specifically targeting the IG2 domain inhibited coxsackievirus binding alone, confirming distinct, non-overlapping interaction sites for the two viruses.

Structured PICO

Population

Rodent models (embryonic and adult) and cell models for site-directed mutagenesis

Intervention

Site-directed mutagenesis of the IG1 region of the coxsackievirus group B and adenovirus receptor (HCVADR)

Outcome

Tissue distribution of the receptor and viral binding (Ad5 vs CVB3)surrogate

The study demonstrates that adenovirus and coxsackievirus B bind to distinct, non-overlapping regions of their shared cellular receptor.

Cite This Study

Tomko et al. (2000) studied this question. Site-directed mutagenesis of the IG1 region was evaluated on Ad5 binding and CVB attachment. Site-directed mutagenesis of the IG1 region completely inhibited Ad5 binding without affecting CVB attachment, indicating their molecular interactions with the receptor do not overlap.

synapsesocial.com/papers/6aa38418dd5797a3831aa0aa https://doi.org/10.1006/excr.1999.4761

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Implication

Remains preclinical in rodent models; leaves open whether IG1 mutagenesis can selectively block adenovirus without affecting coxsackievirus in humans.

Expression of the Adenovirus Receptor and Its Interaction with the Fiber Knob

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Expression of the Adenovirus Receptor and Its Interaction with the Fiber Knob

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Also Consider

Also Consider