Feline Foamy Virus Infection: Characterization of Experimental Infection and Prevalence of Natural Infection in Domestic Cats with and without Chronic Kidney Disease

Abstract

Foamy viruses (FVs) are globally prevalent retroviruses that establish apparently apathogenic lifelong infections. Feline FV (FFV) has been isolated from domestic cats with concurrent diseases, including urinary syndromes. We experimentally infected five cats with FFV to study viral kinetics and tropism, peripheral blood mononuclear cell (PBMC) phenotype, urinary parameters, and histopathology. A persistent infection of primarily lymphoid tropism was detected with no evidence of immunological or hematologic perturbations. One cat with a significant negative correlation between lymphocytes and PBMC proviral load displayed an expanded FFV tissue tropism. Significantly increased blood urea nitrogen and ultrastructural kidney changes were noted in all experimentally infected cats, though chemistry parameters were not outside of normal ranges. Histopathological changes were observed in the brain, large intestine, and other tissues. In order to determine if there is an association of FFV with Chronic Kidney Disease, we additionally screened 125 Australian pet cats with and without CKD for FFV infection and found that FFV is highly prevalent in older cats, particularly in males with CKD, though this difference was not statistically significant compared to controls. Acute FFV infection was clinically silent, and while some measures indicated mild changes, there was no overt association of FFV infection with renal disease.

Case-Control Study of the Immune Status of Humans Infected With Zoonotic Gorilla Simian Foamy Viruses

“…Here, we only observed CD8 T-cell expansion. As we previously discussed [16] FV establishes wide tissue tropism after natural or experimental infection in NHPs, cats, and cattle, with consistent detection of viral DNA in blood and lymphoid tissues [17,21,[40][41][42]. The separation of lymphocyte subsets from infected individuals showed infection of B and T lymphocytes [13,26,27].…”

“…Despite apparent viral control, infected individuals show elevated inflammation and some ultimately experience clinical disease or loss of viral control[36][37][38]. The present data and those obtained on hematological parameters and specific antibodies challenge the proposed SFV latency in humans, simians and felines[2,[14][15][16][17]39].…”

“…Although we observed immune differences between SFV-infected individuals and carefully matched controls, we cannot conclude that they are a direct consequence of SFV infection. However, the experimental infection of cats supports the causal relationship between FV infection, persistent lymphocytic infiltration in peripheral organs, and histological features in kidneys [17]. Importantly, the biological findings in SFV-infected hunters are plausible consequences of viral infection.…”

“…Experimental inoculation of feline FV (FFV) to young, healthy, and specific pathogen-free cats leads to persistent infection, without clinical signs, over the first six months. FFV infection induces mild to moderate blood urea levels, an increased protein:creatinine ratio in urine, and histopathological and ultrastructural changes in the kidneys [17].…”

Bovine Foamy Virus: Shared and Unique Molecular Features In Vitro and In Vivo

“…An interesting feature of FVs is their ability to infect a diverse range of cell types and cause a characteristic foam-like cytopathic effect in culture system. However, they appear to be non-pathogenic in either naturally or accidentally infected hosts with a currently "emerging" but still ill-defined capacity to affect blood or kidney parameters without overt clinical consequences [11,95,96]. This suggests that the host immune system controls viral infection and/or FV replication in vivo.…”