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Replication and pathogenicity of attenuated human metapneumovirus F mutants in severe combined immunodeficiency mice
Chun-mei Yu1, Rong-pei Li, Xin Chen
1Children's Hospital of Chongqing Medical University, Chongqing, China.
Abstract:
This study was to evaluate the replication and pathogenicity of attenuated human metapneumovirus (HMPV) mutants in severe combined immunodeficiency (SCID) mice. SCID mice were intranasally infected with either wild type GFP-rHMPV (WT), or mutant viruses (M1, M2 and M4) with the N-linked glycosylation(s) of the F protein removed. The organs were collected for viral isolation, titration, pulmonary histopathology and mRNA detection by PCR at different time points. WT or mutant viruses were successfully isolated from the lungs of infected mice after inoculation. The titers of WT and M1 peaked on 5th day and remained detectable until 14th day post-inoculation. M2 reached approximately 4 logs lower titer on 5th and 9th day post-inoculation as compared to WT and M1. M4 showed similar growth kinetics to M2. Viral signal was never detected from the heart, liver, spleen, kidney and brain on 5th day post-inoculation. The pulmonary pathology score in the M1 infected mice was similar to WT infected mice but higher than in M2 or M4 infected mice. WT and HMPV mutants can thus only replicate in the lungs of SCID mice. Attenuated M2 and M4 may be considered as candidates for the preparation of vaccine against HMPV.
Insights
Attenuated human metapneumovirus (HMPV) mutants M2 and M4 showed reduced replication and pathogenicity in SCID mice. These attenuated HMPV strains are potential vaccine candidates.
Area of Science:
- Virology
- Immunology
- Vaccinology
Background:
- Human metapneumovirus (HMPV) is a significant respiratory pathogen.
- Development of effective HMPV vaccines is crucial for public health.
- Understanding viral attenuation mechanisms is key for vaccine design.
Purpose of the Study:
- To evaluate the replication and pathogenicity of attenuated HMPV mutants in a severe combined immunodeficiency (SCID) mouse model.
- To assess the potential of these attenuated mutants as vaccine candidates against HMPV.
Main Methods:
- SCID mice were intranasally inoculated with wild-type (WT) GFP-rHMPV or F protein N-linked glycosylation mutants (M1, M2, M4).
- Viral isolation, titration, pulmonary histopathology, and mRNA detection via PCR were performed on collected organs at various time points.
- Replication and pathogenicity were assessed by viral load, tissue distribution, and lung pathology scoring.
Main Results:
- WT and mutant HMPV were isolated from the lungs of infected SCID mice.
- Mutants M2 and M4 exhibited significantly lower viral titers and reduced pulmonary pathology compared to WT and M1.
- Viral replication was confined to the lungs, with no detection in other organs.
Conclusions:
- Attenuated HMPV mutants M2 and M4 demonstrate reduced replication and pathogenicity in SCID mice.
- These attenuated strains show promise as candidates for developing a safe and effective HMPV vaccine.
