Effects of G and SH Truncation on the Replication, Virulence, and Immunogenicity of Avian Metapneumovirus

Author:

Hong Seung-Min12,Ha Eun-Jin12ORCID,Kim Ho-Won12,Kim Seung-Ji12,Ahn Sun-Min12ORCID,An Se-Hee3ORCID,Kim Gun4ORCID,Kim Suji5,Kwon Hyuk-Joon2678ORCID,Choi Kang-Seuk12ORCID

Affiliation:

1. Laboratory of Avian Diseases, Department of Farm Animal Medicine, College of Veterinary Medicine and BK21 PLUS for Veterinary Science, Seoul National University, Seoul 088026, Republic of Korea

2. Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul 08826, Republic of Korea

3. Animal and Plant Quarantine Agency, Gimcheon 39660, Republic of Korea

4. Laboratory of Veterinary Pharmacology, Research Institute of Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul 088026, Republic of Korea

5. Department of Nuclear Medicine, Seoul National University Bundang Hospital, Seongnam 13620, Republic of Korea

6. Laboratory of Poultry Medicine, Department of Farm Animal Medicine, College of Veterinary Medicine and BK21 PLUS for Veterinary Science, Seoul National University, Seoul 088026, Republic of Korea

7. Institutes of Green-bio Science Technology (GBST), Farm Animal Clinical Training and Research Center (FACTRC), Seoul National University, Pyeongchang 25354, Republic of Korea

8. GeNiner Inc., Seoul 08826, Republic of Korea

Abstract

Four mutants varying the length of the G and SH genes, including a G-truncated mutant (ΔG) and three G/SH-truncated mutants (ΔSH/G-1, ΔSH/G-2, and ΔSH/G-3), were generated via serially passaging the avian metapneumovirus strain SNU21004 into the cell lines Vero E6 and DF-1 and into embryonated chicken eggs. The mutant ΔG particles resembled parental virus particles except for the variance in the density of their surface projections. G and G/SH truncation significantly affected the viral replication in chickens’ tracheal ring culture and in infected chickens but not in the Vero E6 cells. In experimentally infected chickens, mutant ΔG resulted in the restriction of viral replication and the attenuation of the virulence. The mutants ΔG and ΔSH/G-1 upregulated three interleukins (IL-6, IL-12, and IL-18) and three interferons (IFNα, IFNβ, and IFNγ) in infected chickens. In addition, the expression levels of innate immunity-related genes such as Mda5, Rig-I, and Lgp2, in BALB/c mice were also upregulated when compared to the parental virus. Immunologically, the mutant ΔG induced a strong, delayed humoral immune response, while the mutant ΔSH/G-1 induced no humoral immune response. Our findings indicate the potential of the mutant ΔG but not the mutant ΔSH/G-1 as a live attenuated vaccine candidate.

Funder

New Faculty Startup Fund from Seoul National University

Research Institute of Veterinary Science of Seoul National University’s BK21 program

Publisher

MDPI AG

Subject

Pharmacology (medical),Infectious Diseases,Drug Discovery,Pharmacology,Immunology

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