Pneumopathogenicity in mice of a Sendai virus mutant, TSrev-58, is accompanied by in vitro activation with trypsin

Area of Science:

• Virology
• Pathogen Research
• Molecular Biology

Background:

• Sendai virus, a paramyxovirus, causes respiratory infections.
• Viral pathogenicity is often linked to the activation of viral proteins, such as the F protein, by host proteases.
• Understanding the factors influencing Sendai virus lung pathogenicity is crucial for disease control.

Purpose of the Study:

• To investigate the pneumopathogenicity of a trypsin-sensitive revertant (TSrev-58) of Sendai virus in a mouse model.
• To determine if in vitro trypsin sensitivity correlates with in vivo lung pathogenicity.
• To compare the pathogenicity of TSrev-58 with its parental trypsin-resistant mutant (TR-5) and the wild-type virus.

Main Methods:

• Generation of a trypsin-sensitive revertant (TSrev-58) from a trypsin-resistant mutant (TR-5) of Sendai virus.
• Characterization of amino acid substitutions in the F protein cleavage site of TSrev-58.
• Assessment of pneumopathogenicity of TSrev-58, TR-5, and wild-type Sendai virus in mice.
• Correlation analysis between in vitro trypsin sensitivity and in vivo lung pathogenicity.

Main Results:

• TSrev-58 exhibited trypsin sensitivity similar to the wild-type virus, with a single amino acid substitution at residue 116 (Ile----Arg) on the F protein.
• Despite a different amino acid difference at residue 109 (Asn----Asp) compared to the wild-type, TSrev-58 demonstrated equivalent pneumopathogenicity in mice.
• The study confirmed that the protease activating Sendai virus in mouse lungs is highly similar to trypsin.

Conclusions:

• In vitro trypsin sensitivity of Sendai virus serves as a reliable marker for its pneumopathogenicity in mice.
• The activating protease in mouse lungs closely resembles trypsin in its interaction with Sendai virus.
• These findings contribute to understanding the mechanisms of Sendai virus pathogenesis and host-pathogen interactions.