Friend viral pathogenesis in C57BL/6 reversible DBA/2 allophenic mice

Area of Science:

• Virology
• Immunology
• Genetics

Background:

• Friend erythroleukemia virus infection in mice leads to erythroid precursor proliferation, splenomegaly, and reticulocytosis.
• Mouse strain susceptibility to Friend virus varies, with the Fv-2 gene significantly influencing the early response to infection.

Purpose of the Study:

• To investigate whether Friend virus susceptibility/resistance is cell-autonomous or influenced by interactions between cells of different genotypes.
• To determine the role of Fv-2 genotype in Friend virus pathogenesis using allophenic mice.

Main Methods:

• Allophenic mice, created from resistant (C57BL/6, Fv-2rr) and susceptible (DBA/2, Fv-2ss) mouse strains, were infected with Friend virus.
• Viral pathogenesis was monitored by splenomegaly, reticulocytosis, and leukocytosis.
• Red blood cell genotype proportions were analyzed using strain-specific electrophoretic variants of hemoglobin and glucose phosphate isomerase.

Main Results:

• Allophenic mice with ≥25% susceptible-strain red blood cells developed Friend virus disease, with increased susceptible-strain red cells.
• No evidence of resistant-strain cells protecting susceptible-strain cells was observed when susceptible cells predominated.
• Mice with ≤15% susceptible-strain red blood cells showed significantly retarded Friend disease development.

Conclusions:

• Friend virus disease development is primarily driven by susceptible-strain cells, with no protective effect from resistant-strain cells when susceptible cells are abundant.
• Resistant-strain cells may offer protection to susceptible-strain cells, potentially inhibiting viral replication or involving immune mechanisms, when resistant cells are in the majority.
• The Fv-2 genotype plays a critical role in determining the cellular response to Friend virus infection.