Expression of APOBEC3 Lentiviral Restriction Factors in Cats

Area of Science:

• Virology
• Immunology
• Genetics

Background:

• Feline immunodeficiency virus (FIV) is a lentiviral disease in cats, analogous to HIV/AIDS in humans.
• Feline APOBEC3 (A3) proteins are known to restrict FIV infection, with viral Vif protein mediating A3 degradation.
• Host-specific interactions and the role of A3 in FIV pathogenesis are not fully understood.

Purpose of the Study:

• To investigate the expression patterns of feline A3 genes (A3Z2, A3Z3, A3Z2-Z3) during FIV and puma lentivirus (PLV) infections.
• To determine how FIV and PLV infection, as well as cytokine treatments, affect A3 gene expression in various feline tissues and cell types.
• To correlate A3 expression levels with viral replication kinetics in different feline blood cell subpopulations.

Main Methods:

• Experimental infection of domestic cats with FIV and PLV, including co-infection models.
• Quantification of A3Z2, A3Z3, and A3Z2-Z3 mRNA abundance in tissues and blood cells using RT-qPCR.
• Analysis of A3 expression in purified blood cell subpopulations (T cells, B cells, monocytes).
• In vitro studies evaluating A3 expression regulation by cytokines (IFN-α, IFN-γ) and mitogens in cultured feline cells.

Main Results:

• A3Z3 mRNA was significantly more abundant (over 300-fold) than A3Z2-Z3 mRNA across all feline tissues and cells studied.
• Interferon-alpha upregulated A3 expression in cat T cells, while interferon-gamma enhanced expression in cat cell lines.
• Basal A3 expression was highest in secondary lymphoid organs and peripheral blood mononuclear cells (PBMC), with differential expression among blood cell subsets.
• Acute FIV and PLV infections generally did not alter A3 expression, except for elevated levels in the thymus; FIV infection of PBMC also showed no significant change in A3 expression.

Conclusions:

• Feline A3 gene expression is influenced by cytokine treatment but largely unaffected by lentiviral infection.
• Differential A3 expression in blood cell subsets does not appear to dictate FIV replication rates.
• The high abundance of A3Z3 mRNA suggests it plays a primary role as an anti-lentiviral factor in domestic cats.