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Feline Adenovirus Isolate Shows Silent Nucleotide Alterations, Alternative Receptor/Coreceptor Binding, High
Katalin Réka Tarcsai1, Krisztián Bányai2,3,4,5, Krisztina Bali2,6
1Doctoral School, Semmelweis University, 1085 Budapest, Hungary.
Abstract:
Adenovirus (AdV) infection has been rarely documented in cats and other felids. Partial sequences of the hexon and fiber genes of a Hungarian feline adenovirus isolate (FeAdV isolate) showed a close relationship to human AdV (HAdV) type C1. Further molecular and biological characterization is reported here. Whole-genome sequencing revealed two silent mutations in the genome of the FeAdV isolate compared to a HAdV-C1 reference strain (at positions 14,096 and 15,082). Competitive antibody binding to the Coxsackie-adenovirus receptor and αvβ3 and αvβ5 integrin coreceptors inhibited the binding of the FeAdV isolate in different cell lines, but residual infections suggested alternative entry routes. The FeAdV isolate was found to be more sensitive to heat, low pH and detergents, but more resistant to alkaline and free chlorine treatments, as well as to ribavirin, stavudine and cidofovir treatments, than other human AdV types. We observed a suppression of IL-10 and TGF-β1 production during the entire course of viral replication. This immunomodulation may restore intratumoral immunity; thus, the FeAdV isolate could serve as an alternative oncolytic vector. Collectively, our results support that the Hungarian FeAdV isolate is a variant of common HAdV-C1. The cohabitation of cats with humans might result in reverse zoonotic infection. Felids appear to be susceptible to persistent and productive adenovirus infection, but further studies are needed to better understand the clinical and epidemiological implications.
Insights
A rare feline adenovirus (FeAdV) isolate in Hungary is a variant of human adenovirus C1. This finding suggests potential reverse zoonotic infections and highlights FeAdV as a possible oncolytic vector.
Area of Science:
- Virology
- Molecular Biology
- Immunology
Background:
- Adenovirus (AdV) infections are seldom reported in felines.
- A Hungarian feline adenovirus (FeAdV) isolate shares genetic similarities with human adenovirus C1 (HAdV-C1).
Purpose of the Study:
- To conduct comprehensive molecular and biological characterization of the Hungarian FeAdV isolate.
- To evaluate its potential as an oncolytic vector.
Main Methods:
- Whole-genome sequencing to identify genetic variations.
- Competitive binding assays using known adenovirus receptors and integrin coreceptors.
- Assessment of viral sensitivity to various environmental conditions and antiviral treatments.
- Analysis of host immune response, specifically cytokine production (IL-10, TGF-β1).
Main Results:
- The FeAdV isolate possesses two silent mutations compared to HAdV-C1.
- While coreceptors are involved in binding, alternative entry routes exist.
- The isolate exhibits differential sensitivity to heat, pH, detergents, disinfectants, and antiviral drugs compared to human adenoviruses.
- Viral replication suppressed IL-10 and TGF-β1 production, indicating immunomodulatory effects.
Conclusions:
- The Hungarian FeAdV isolate is a variant of HAdV-C1, suggesting potential for reverse zoonotic transmission from cats to humans.
- Its unique properties, including immunomodulation, position it as a potential candidate for oncolytic virotherapy.
- Further research is necessary to elucidate the clinical and epidemiological significance of FeAdV in felids.
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