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Recombinant rabies virus expressing interleukin-6 enhances the immune response in mouse brain

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Abstract

Rabies, which is caused by the rabies virus (RABV), is an ancient zoonosis that has a high mortality rate. Previous studies have indicated that recombinant RABV expressing canine interleukin-6 (rHEP-CaIL6), induced more virus-neutralizing antibodies than parental RABV in mice following intramuscular immunization. To investigate the immune response induced in the CNS by rHEP-CaIL6 after intranasal or intracranial administration in mice, the permeability of the blood-brain barrier (BBB), the infiltration of CD3 T cells, and innate immune response-related effector molecules in the CNS were examined. It was observed that infection of rHEP-CaIL6 led to enhanced BBB permeability following intranasal infection. More CD3 T cells infiltrated into the central nervous system (CNS) in mice infected with rHEP-CaIL6 than in those infected with the HEP-Flury strain. Furthermore, rHEP-CaIL6 induced an increased expression of innate immune response-related effector molecules, compared with the parental HEP-Flury strain, within the CNS. Taken together, these findings suggest that rHEP-CaIL6 induced stronger immune responses in mice brains, which is more beneficial for virus clearance. These results may also partly illustrate the role of IL6 in RABV infection.

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Acknowledgements

We thank the Guangdong Haid Institute of Animal Husbandry and Veterinary Research for providing instruments for our work. This study was partially supported by the Nature Science Foundation of Guangdong (No.2015A03031103), the National Key Research and Development Program of China (No. 2016YFD0500400), the National Nature Science Foundation of China (No.31172322) and the grant from the 2017 Graduate Student Overseas Study Program of South China Agricultural University (2017LHPY028).

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Author notes

  1. Jun Luo, Boyue Zhang, Yuting Wu and Qin Tian contributed equally to this work.

Authors and Affiliations

  1. College of Veterinary Medicine, South China Agricultural University, No. 483 Wushan Street, Guangzhou, 510642, China

    Jun Luo, Boyue Zhang, Yuting Wu, Qin Tian, Meijun Mo, Teng Long, Mingzhu Mei, Ruqi Fan, Ziyu Lyu, He Jiang, Fan Wu, Yingyi Lin & Xiaofeng Guo

  2. Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, Guangzhou, People’s Republic of China

    Jun Luo, Boyue Zhang, Yuting Wu, Qin Tian, Meijun Mo, Teng Long, Mingzhu Mei, Ruqi Fan, Ziyu Lyu, He Jiang, Fan Wu, Yingyi Lin & Xiaofeng Guo

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  1. Jun Luo
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Correspondence to Xiaofeng Guo.

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The authors declare that they have no conflict of interest.

Ethical approval

All procedures involving animals were approved by the Ethics Committee for Animal Experiments at South China Agricultural University. All animal experiments were carried out in strict accordance with international, national and institutional guidelines for the use and care of animals.

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Handling Editor: Diego G. Diel.

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Luo, J., Zhang, B., Wu, Y. et al. Recombinant rabies virus expressing interleukin-6 enhances the immune response in mouse brain. Arch Virol 163, 1889–1895 (2018). https://doi.org/10.1007/s00705-018-3808-8

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  • DOI: https://doi.org/10.1007/s00705-018-3808-8

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