Presence of Endogenous Viral Elements Negatively Correlates with Feline Leukemia Virus Susceptibility in Puma and Domestic Cat Cells

• Published in: Journal of virology 2020-10, Vol.94 (21)
• Main Authors: Chiu, Elliott S, VandeWoude, Sue
• Format: Article
• Language: English
• Subjects: Animals; Bone Marrow - pathology; Bone Marrow - virology; Cats; DNA Copy Number Variations; Female; Fibroblasts - pathology; Fibroblasts - virology; Gene Products, env - genetics; Gene Products, env - metabolism; Host Specificity; Leukemia Virus, Feline - genetics; Leukemia Virus, Feline - metabolism; Leukemia Virus, Feline - pathogenicity; Leukemia, Feline - pathology; Leukemia, Feline - virology; Lymph Nodes - pathology; Lymph Nodes - virology; Male; Primary Cell Culture; Puma - virology; Spleen - pathology; Spleen - virology; Terminal Repeat Sequences; Thymus Gland - pathology; Thymus Gland - virology; Viral Load; Virus Replication - genetics; Virus-Cell Interactions
• ISSN: 0022-538X; 1098-5514
• DOI: 10.1128/JVI.01274-20

While feline leukemia virus (FeLV) has been shown to infect felid species other than the endemic domestic cat host, differences in FeLV susceptibility among species has not been evaluated. Previous reports have noted a negative correlation between endogenous FeLV (enFeLV) copy number and exogenous FeLV (exFeLV) infection outcomes in domestic cats. Since felids outside the genus do not harbor enFeLV genomes, we hypothesized absence of enFeLV results in more severe disease consequences in felid species lacking these genomic elements. We infected primary fibroblasts isolated from domestic cats ( ) and pumas ( ) with FeLV and quantitated proviral and viral antigen loads. Domestic cat enFeLV and long terminal repeat (LTR) copy numbers were determined for each individual and compared to FeLV viral outcomes. FeLV proviral and antigen levels were also measured in 6 naturally infected domestic cats and 11 naturally infected Florida panthers ( ). We demonstrated that puma fibroblasts are more permissive to FeLV than domestic cat cells, and domestic cat FeLV restriction was highly related to enFeLV-LTR copy number. Terminal tissues from FeLV-infected Florida panthers and domestic cats had similar exFeLV proviral copy numbers, but Florida panther tissues have higher FeLV antigen loads. Our work indicates that enFeLV-LTR elements negatively correlate with exogenous FeLV replication. Further, samples lacking enFeLV are more permissive to FeLV infection than domestic cat samples, suggesting that endogenization can play a beneficial role in mitigating exogenous retroviral infections. Conversely, presence of endogenous retroelements may relate to new host susceptibility during viral spillover events. Feline leukemia virus (FeLV) can infect a variety of felid species. Only the primary domestic cat host and related small cat species harbor a related endogenous virus in their genomes. Previous studies noted a negative association between the endogenous virus copy number and exogenous virus infection in domestic cats. This report shows that puma cells, which lack endogenous FeLV, produce more virus more rapidly than domestic cat fibroblasts following cell culture challenge. We document a strong association between domestic cat cell susceptibility and FeLV long terminal repeat (LTR) copy number, similar to observations in natural FeLV infections. Viral replication does not, however, correlate with FeLV copy number, suggesting that this effect is specific to FeLV-LTR elements. T