Kupffer and endothelial liver cell damage renders A/J mice susceptible to mouse hepatitis virus type 3

Area of Science:

• Virology
• Immunology
• Hepatology

Background:

• A/J mice are genetically resistant to mouse hepatitis virus type 3 (MHV 3).
• Kupffer and endothelial cells form the liver sinusoidal lining, crucial for liver immunity.
• The role of these cells in MHV 3 resistance is not fully understood.

Purpose of the Study:

• To investigate if damage to liver sinusoidal cells affects MHV 3 susceptibility in A/J mice.
• To elucidate the role of the liver sinusoidal lining in innate resistance to MHV 3.

Main Methods:

• Administration of sublethal doses of frog virus 3 (FV 3) to A/J mice.
• Infection of FV 3-pretreated mice with MHV 3.
• Assessment of liver histopathology, viral antigen presence, serum transaminase levels (GPT), and MHV 3 viral titers.

Main Results:

• FV 3-induced damage to Kupffer and endothelial cells rendered genetically resistant A/J mice highly susceptible to MHV 3.
• Histopathology revealed necrotic foci with MHV 3 antigens in infected mice.
• FV 3-pretreated mice exhibited elevated GPT levels and increased MHV 3 replication rates and titers.

Conclusions:

• The liver sinusoidal lining plays a critical role in protecting hepatocytes from viral infection.
• Damage to these sinusoidal cells directly impacts the innate resistance of A/J mice to MHV 3.
• This study underscores the importance of sinusoidal cells in controlling viral hepatitis.