Infection and replication of human adenovirus type 3 possessing type 5 fiber protein in rodent cells
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Published on: November 12, 2015
Tiantian Liu1, Mei Wang2, Zhichao Zhou3
1School of Public Health, Guangdong Pharmaceutical University, Guangzhou, Guangdong, 510310, China; State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China.
Abstract:
Human adenovirus (HAdV) is an important respiratory pathogen in children that often leads to wider outbreaks of acute respiratory tract infection. HAdV group B contains the most important serotypes, HAdV-3 and HAdV-7, responsible for infection of humans. However, due to the species barrier, there is no suitable and effective animal model of HAdV-B for drug and vaccine development. Here we generated a recombinant capsid-chimeric HAdV-3, rAd3E-Fk5, by replacing the HAdV-3 fiber gene with that of the group C, type 5 virus. The rAd3E-Fk5 virus infected and replicated efficiently in both BALB/c mice and golden hamster primary kidney epithelial cells. However, the infectivity of the parent HAdV-3 virus was very low in hamster primary kidney cells. The infectivity of the recombinant rAd3E-Fk5 virus was also confirmed by staining for viral late protein, hexon, in infected primary rodent cells. These results indicate that the fiber protein may be a limiting factor in determining the species specificity of HAdV-3. This chimeric virus may be useful for developing an animal model of HAdV-3 infection, for vaccine and antiviral drug evaluation and for determination of the pathogenic mechanisms of HAdV-B.
Insights
A new chimeric human adenovirus type 3 (HAdV-3) virus efficiently infects rodent cells, overcoming species barriers. This breakthrough facilitates the development of animal models for studying HAdV-B infections and evaluating vaccines and drugs.
Area of Science:
- Virology
- Immunology
- Infectious Diseases
Background:
- Human adenovirus (HAdV) causes significant respiratory infections in children, with HAdV group B (HAdV-B) serotypes like HAdV-3 and HAdV-7 being major pathogens.
- Existing species barriers limit the development of effective animal models for HAdV-B, hindering drug and vaccine research.
Purpose of the Study:
- To engineer a recombinant HAdV-3 with altered species tropism for improved animal model development.
- To investigate the role of the fiber protein in HAdV-3 species specificity.
Main Methods:
- Generation of a chimeric HAdV-3 (rAd3E-Fk5) by replacing the HAdV-3 fiber gene with that of HAdV-C5.
- Testing the infectivity and replication of rAd3E-Fk5 in primary kidney epithelial cells from BALB/c mice and golden hamsters.
- Comparing infectivity of rAd3E-Fk5 with the parent HAdV-3 virus.
- Confirming viral infection via hexon protein staining.
Main Results:
- The recombinant virus rAd3E-Fk5 demonstrated efficient infection and replication in both mouse and hamster primary kidney cells.
- The parent HAdV-3 virus showed very low infectivity in hamster primary kidney cells.
- Hexon staining confirmed the presence of the virus in infected primary rodent cells.
Conclusions:
- The fiber protein is a critical determinant of HAdV-3 species specificity.
- The chimeric virus rAd3E-Fk5 shows promise as a tool for developing HAdV-3 animal models.
- This recombinant virus can aid in evaluating HAdV-B vaccines, antiviral drugs, and pathogenic mechanisms.
