Zoonotic Potential of Canine Adenovirus: Insights into Evolutionary Adaptation to Humans
Creators: name: Hussain, Zahid
Publisher: name: Zenodo
Year: 2024
Subjects: Zoonotic
Potential
Canine Adenovirus:
Insights into
Evolutionary Adaptation
Humans

description: Zoonotic Potential of Canine Adenovirus: Insights into Evolutionary Adaptation to Humans

Abstract 

Canine Adenovirus (CAdV), a DNA virus primarily infecting dogs, poses a potential zoonotic risk if it acquires specific mutations allowing efficient human infection. This report examines the molecular mechanisms and evolutionary pathways necessary for CAdV adaptation to human hosts. Key targets include the fiber knob protein for receptor binding, the hexon protein for immune evasion, and the penton base protein for cellular internalization. Analysis indicates that 7–13 mutations across these proteins and immune modulation genes may enable human adaptation. Experimental studies and observational data from other zoonotic adenoviruses highlight potential pathways for such evolution. Enhanced surveillance of CAdVs in canine and human populations is crucial for monitoring and mitigating potential zoonotic threats.

Introduction Canine Adenovirus (CAdV) exists in two serotypes: CAdV-1, causing infectious canine hepatitis, and CAdV-2, associated with respiratory disease. Although adenoviruses generally display host specificity, zoonotic transmission remains a concern, given the adaptability observed in other adenovirus species. This report investigates the molecular and evolutionary requirements for CAdV to adapt to human hosts, emphasizing receptor binding, immune evasion, and replication efficiency.

Key Factors for Adaptation

1. Fiber Knob Protein (Receptor Binding) The fiber knob protein is critical for host cell attachment by interacting with specific cellular receptors. Human adenoviruses (HAdVs) predominantly utilize the coxsackievirus and adenovirus receptor (CAR) and integrins such as αvβ3 and αvβ5. In contrast, CAdVs target canine-specific receptors. Adaptation would require mutations enabling recognition and binding to human receptors.



Residues 240–260 (Receptor-Binding Region): Alterations in this region could facilitate binding to CAR.

Residues 415–430 (Binding Pocket): Mutations here may enhance compatibility with human integrins or CAR.


2. Hexon Protein (Immune Evasion) The hexon protein, the largest structural component of the adenoviral capsid, determines antigenicity. Modifications in hypervariable regions (HVRs) can help evade host immune responses by reducing neutralization by human antibodies.



Hypervariable Regions (HVRs 200–400): Targeted mutations may obscure critical epitopes, enhancing immune evasion.


3. Penton Base Protein (Internalization) The penton base protein mediates viral internalization through interactions with integrins, employing the Arg-Gly-Asp (RGD) motif. Adaptation to human integrins would require mutations optimizing these interactions.



RGD Motif: Modifications could improve binding to human integrins αvβ3 or αvβ5, enhancing internalization efficiency.


4. E3 Region (Immune Modulation) The E3 region encodes proteins involved in immune evasion. For CAdV to evade human immune defenses, adaptations in this region are necessary.



E3/19K Protein: Changes here might inhibit MHC class I presentation, reducing recognition by human cytotoxic T cells.


Potential Mutations Required



Fiber Knob Protein: 3–5 mutations.

Hexon Protein: 2–4 mutations in HVRs.

Penton Base Protein: 1–2 mutations in the RGD motif.

E3 Region: 1–2 mutations.


In total, 7–13 mutations across these proteins are estimated to enable full adaptation to humans.

Experimental and Observational Evidence

Human Adenovirus Adaptation Studies of zoonotic adenoviruses provide valuable insights:



Simian Adenoviruses (SAdVs): Closely related to HAdVs, SAdVs required fewer than ten mutations to adapt to human receptors and evade immune defenses.

Bovine Adenoviruses (BAdVs): Cross-species transmission studies demonstrate similar mutation patterns facilitating host adaptation.


CAdV Experimental Evolution Serial passage experiments in human cell cultures can simulate selective pressure, revealing mutations that enhance compatibility with human hosts. Such studies on adenoviruses demonstrate rapid evolution under controlled conditions, often within months to years.

Timeline for Adaptation

1. Without Selective Pressure



Random mutation accumulation in natural settings could take decades to centuries.


2. Under Selective Pressure



Frequent human exposure, such as through close contact with infected dogs, might accelerate adaptation within 5–20 years.


3. Laboratory Evolution



Directed evolution via serial passage in human cells could produce adaptive mutations in months to a few years.


Conclusion



Number of Mutations Required: 7–13 mutations.

Key Sites:



Fiber Knob Protein: Residues 240–260 and 415–430.

Hexon Protein: HVRs (200–400).

Penton Base Protein: RGD motif.

E3 Region: Immune modulation proteins.


Adaptation Timeline: Evolution could occur in 5–20 years under selective pressure or faster in experimental settings.


Recommendations Enhanced surveillance of CAdVs in canine and human populations is essential to monitor potential zoonotic risks. Genomic studies should focus on the identified key regions to track mutations indicative of human adaptation. Furthermore, experimental evolution studies could provide insights into mutation pathways and inform preventive strategies.

References