Multiple Introductions of Domestic Cat Feline Leukemia Virus in Endangered Florida Panthers1

Visceral leishmaniasis (VL) is expanding in the Brazilian territory. Dogs are considered an important urban reservoir; however, studies have demonstrated the presence of infected cats in some Brazilian states. This report aimed to describe a case of Leishmania (Leishmania) infantum infection in a two-month-old domestic feline from a Brazilian region with a high incidence of human visceral leishmaniasis. The analyzed samples were the cat’s blood, conjunctiva, spleen, liver, popliteal, submandibular and mesenteric lymph nodes, skin, lung and kidney. The diagnostic methods were: parasitological examination, polymerase chain reaction (PCR) and an immunoflurescence antibody test (IFAT). All tissues were positive. The title obtained using the IFAT was 1:160. The animal was negative for feline immunodeficiency virus (FIV) and feline leukemia virus (FeLV). This work addresses the first case of feline leishmaniasis in the state of Tocantins, and reveals data that may contribute to the knowledge of the disease, since it has been shown to be able to develop rapidly and fatally in kittens, with the ability to infect several tissues.

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

Journal of Virology ◽

10.1128/jvi.01274-20 ◽

2020 ◽

Vol 94 (21) ◽

Author(s):

Elliott S. Chiu ◽

Sue VandeWoude

Keyword(s):

Copy Number ◽

Puma Concolor ◽

Leukemia Virus ◽

Domestic Cat ◽

Feline Leukemia Virus ◽

Domestic Cats ◽

Endogenous Virus ◽

Content Type ◽

Copy Numbers ◽

Felid Species

ABSTRACT 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 Felis 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 (Felis catus) and pumas (Puma concolor) with FeLV and quantitated proviral and viral antigen loads. Domestic cat enFeLV env 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 (P. concolor coryi). 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, Puma concolor 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. IMPORTANCE 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 env copy number, suggesting that this effect is specific to FeLV-LTR elements. This discovery indicates a protective capacity of the endogenous virus against the exogenous form, either via direct interference or indirectly via gene regulation, and may suggest evolutionary outcomes of retroviral endogenization.

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Endogenous feline leukemia virus siRNA transcription may interfere with exogenous FeLV infection

10.1101/2021.01.12.426481 ◽

2021 ◽

Author(s):

Elliott S. Chiu ◽

Sue VandeWoude

Keyword(s):

Mononuclear Cells ◽

Cell Function ◽

Leukemia Virus ◽

Endogenous Retroviruses ◽

Domestic Cat ◽

Feline Leukemia Virus ◽

Infectious Agents ◽

Biological Functions ◽

Peripheral Blood Mononuclear ◽

Solo Ltrs

AbstractEndogenous retroviruses (ERVs) are increasingly recognized for biological impacts on host cell function and susceptibility to infectious agents, particularly in relation to interactions with exogenous retroviral progenitors (XRVs). ERVs can simultaneously promote and restrict XRV infections using different mechanisms that are virus- and host-specific. The majority of endogenous-exogenous retroviral interactions have been evaluated in experimental mouse or chicken systems which are limited in their ability to extend findings to naturally infected outbred animals. Feline leukemia virus (FeLV) has a relatively well-characterized endogenous retrovirus with a coexisting virulent exogenous counterpart and is endemic worldwide in domestic cats. We have previously documented an association between endogenous FeLV LTR copy number and abrogated exogenous FeLV in naturally infected cats and experimental infections in tissue culture. Analyses described here examine limited FeLV replication in experimentally infected peripheral blood mononuclear cells. We further examine NCBI Sequence Read Archive RNA transcripts to evaluate enFeLV transcripts and RNA interference precursors. We find that lymphoid-derived tissues, which are experimentally less permissive to exogenous FeLV infection, transcribe higher levels of enFeLV under basal conditions. Transcription of enFeLV-LTR segments is significantly greater than other enFeLV genes. We documented transcription of a 21-nt miRNA just 3′ to the enFeLV 5′-LTR in the feline miRNAome of all datasets evaluated (n=27). Our findings point to important biological functions of enFeLV transcription linked to solo LTRs distributed within the domestic cat genome, with potential impacts on domestic cat exogenous FeLV susceptibility and pathogenesis.ImportanceEndogenous retroviruses (ERVs) are increasingly implicated in host cellular processes and susceptibility to infectious agents, specifically regarding interactions with exogenous retroviral progenitors (XRVs). Exogenous feline leukemia virus (FeLV) and its endogenous counterpart (enFeLV) represent a well characterized, naturally occurring XRV-ERV dyad. We have previously documented an abrogated FeLV infection in both naturally infected cats and experimental fibroblast infections that harbor higher enFeLV proviral loads. Using an in silico approach, we provide evidence of miRNA-transcription that are produced in tissues most important for FeLV infection, replication, and transmission. Our findings point to important biological functions of enFeLV transcription linked to solo-LTRs distributed within the feline genome, with potential impacts on domestic cat exogenous FeLV susceptibility and pathogenesis. This body of work provides additional evidence of RNAi as a mechanism of viral interference and is a demonstration of ERV exaptation by the host to defend against related XRVs.

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Presence of endogenous viral elements negatively correlates with FeLV susceptibility in puma and domestic cat cells

10.1101/2020.06.23.168351 ◽

2020 ◽

Author(s):

Elliott S. Chiu ◽

Sue VandeWoude

Keyword(s):

Copy Number ◽

Puma Concolor ◽

Leukemia Virus ◽

Domestic Cat ◽

Feline Leukemia Virus ◽

Host Susceptibility ◽

Domestic Cats ◽

Endogenous Virus ◽

Copy Numbers ◽

Felid Species

AbstractWhile 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 enFeLV copy number and exogenous FeLV infection outcomes in domestic cats. Since felids outside the genus Felis 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 (Felis catus) and pumas (Puma concolor) with FeLV and quantitated proviral and viral antigen loads. Domestic cat enFeLV env and 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 (P. concolor coryi). 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 enFeLV LTR elements negatively regulate exogenous FeLV replication. Further, Puma concolor lacking enFeLV are more permissive to FeLV infection than domestic cats, suggesting 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.ImportanceFeline 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 env copy number, suggesting this effect is specific to FeLV LTR elements. This discovery indicates a protective capacity of the endogenous virus against the exogenous form, either via direct interference or indirectly via gene regulation, and may suggest evolutionary outcomes of retroviral endogenization.

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Fatal toxoplasmosis in an immunosuppressed domestic cat from Brazil caused by Toxoplasma gondii clonal type I

Revista Brasileira de Parasitologia Veterinária ◽

10.1590/s1984-29612017025 ◽

2017 ◽

Vol 26 (2) ◽

pp. 177-184 ◽

Cited By ~ 5

Author(s):

Hilda Fátima de Jesus Pena ◽

Camila Mariellen Evangelista ◽

Renata Assis Casagrande ◽

Giovana Biezus ◽

Claudia Salete Wisser ◽

...

Keyword(s):

Toxoplasma Gondii ◽

Histopathological Examination ◽

Leukemia Virus ◽

Fatal Case ◽

Domestic Cat ◽

Feline Leukemia Virus ◽

Type I ◽

Clonal Type ◽

Pcr Rflp ◽

Pcr Targeting

Abstract The objective of the study was to report on a fatal case of feline toxoplasmosis with coinfection with the feline leukemia virus (FeLV). A domestic cat (Felis silvestris catus) presented intense dyspnea and died three days later. In the necropsy, the lungs were firm, without collapse and with many white areas; moderate lymphadenomegaly and splenomegaly were also observed. The histopathological examination showed severe necrotic interstitial bronchopneumonia and mild necrotic hepatitis, associated with intralesional cysts and tachyzoites of Toxoplasma gondii that were positive by anti-T. gondii immunohistochemical (IHC) evaluation. The bone marrow showed chronic myeloid leukemia and the neoplastic cells were positive by anti-FeLV IHC evaluation. DNA extracted from lungs was positive for T. gondii by PCR targeting REP-529. T. gondii was characterized by PCR-RFLP and by the microsatellites technique. ToxoDB-PCR-RFLP #10, i.e. the archetypal type I, was identified. Microsatellite analysis showed that the strain was a variant of type I with two atypical alleles. This was the first time that a T. gondii clonal type I genotype was correlated with a case of acute toxoplasmosis in a host in Brazil.

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Osteochondroma in a young cat infected by feline leukemia virus

Ciência Rural ◽

10.1590/0103-8478cr20151558 ◽

2017 ◽

Vol 47 (1) ◽

Author(s):

Matheus de Oliveira Reis ◽

Lauren Santos de Mello ◽

Kivia Lunardelli Hesse ◽

Marina Paula Lorenzett ◽

Kauê Danilo Helene Lemos dos Reis ◽

...

Keyword(s):

Histopathological Examination ◽

Leukemia Virus ◽

Peripheral Blood Lymphocytes ◽

Domestic Cat ◽

Feline Leukemia Virus ◽

Cartilage Tissue ◽

Pathological Findings ◽

Primary Bone Tumors ◽

Proliferative Lesion ◽

Primary Bone

ABSTRACT: Osteochondromas are primary bone tumors characterized by cartilage-covered bone projections involving single or multiple masses (osteochondromatosis). This study reports the clinical and pathological findings from a young domestic cat with osteochondroma in the humerus. During the clinical evaluation, the animal had pronounced right forelimb musculature atrophy and an increased distal humeral volume. Histopathological examination of the neoplasm revealed a proliferative lesion characterized mostly by endochondral ossification and peripheral foci of proliferating cartilage tissue. Further testing using immunohistochemical staining and polymerase chain reaction revealed the presence of feline leukemia virus antigens in the hematopoietic cells of the bone marrow and FeLV proviral DNA in the peripheral blood lymphocytes. Clinical and pathological findings are consistent with osteochondroma. This neoplasm occurred in an eight-month-old feline with humeral enlargement that had been present since two months old.

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Feline Leukemia Virus (FeLV) Disease Outcomes in a Domestic Cat Breeding Colony: Relationship to Endogenous FeLV and Other Chronic Viral Infections

Journal of Virology ◽

10.1128/jvi.00649-18 ◽

2018 ◽

Vol 92 (18) ◽

Cited By ~ 23

Author(s):

Jordan A. Powers ◽

Elliott S. Chiu ◽

Simona J. Kraberger ◽

Melody Roelke-Parker ◽

Isabella Lowery ◽

...

Keyword(s):

Viral Load ◽

Viral Infections ◽

Leukemia Virus ◽

Domestic Cat ◽

Feline Leukemia Virus ◽

Breeding Colony ◽

Content Type ◽

Viral Loads ◽

Chronic Viral Infections ◽

Disease Outcomes

ABSTRACTExogenous feline leukemia virus (FeLV) is a feline gammaretrovirus that results in a variety of disease outcomes. Endogenous FeLV (enFeLV) is a replication-defective provirus found in species belonging to theFelisgenus, which includes the domestic cat (Felis catus). There have been few studies examining interaction between enFeLV genotype and FeLV progression. We examined point-in-time enFeLV and FeLV viral loads, as well as occurrence of FeLV/enFeLV recombinants (FeLV-B), to determine factors relating to clinical disease in a closed breeding colony of cats during a natural infection of FeLV. Coinfections with feline foamy virus (FFV), feline gammaherpesvirus 1 (FcaGHV-1), and feline coronavirus (FCoV) were also documented and analyzed for impact on cat health and FeLV disease. Correlation analysis and structural equation modeling techniques were used to measure interactions among disease parameters. Progressive FeLV disease and FeLV-B presence were associated with higher FeLV proviral and plasma viral loads. Female cats were more likely to have progressive disease and FeLV-B. Conversely, enFeLV copy number was higher in male cats and negatively associated with progressive FeLV disease. Males were more likely to have abortive FeLV disease. FFV proviral load was found to correlate positively with higher FeLV proviral and plasma viral load, detection of FeLV-B, and FCoV status. Male cats were much more likely to be infected with FcaGHV-1 than female cats. This analysis provides insights into the interplay between endogenous and exogenous FeLV during naturally occurring disease and reveals striking variation in the infection patterns among four chronic viral infections of domestic cats.IMPORTANCEEndogenous retroviruses are harbored by many animals, and their interactions with exogenous retroviral infections have not been widely studied. Feline leukemia virus (FeLV) is a relevant model system to examine this question, as endogenous and exogenous forms of the virus exist. In this analysis of a large domestic cat breeding colony naturally infected with FeLV, we documented that enFeLV copy number was higher in males and inversely related to FeLV viral load and associated with better FeLV disease outcomes. Females had lower enFeLV copy numbers and were more likely to have progressive FeLV disease and FeLV-B subtypes. FFV viral load was correlated with FeLV progression. FFV, FcaGHV-1, and FeLV displayed markedly different patterns of infection with respect to host demographics. This investigation revealed complex coinfection outcomes and viral ecology of chronic infections in a closed population.

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Evolutionary dynamics of endogenous feline leukemia virus proliferation among species of the domestic cat lineage

Virology ◽

10.1016/j.virol.2010.06.010 ◽

2010 ◽

Vol 405 (2) ◽

pp. 397-407 ◽

Cited By ~ 16

Author(s):

Sagi Polani ◽

Alfred L. Roca ◽

Bryan B. Rosensteel ◽

Sergios-Orestis Kolokotronis ◽

Gila Kahila Bar-Gal

Keyword(s):

Evolutionary Dynamics ◽

Leukemia Virus ◽

Domestic Cat ◽

Feline Leukemia Virus

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Endogenous feline leukemia virus siRNA transcription may interfere with exogenous FeLV infection

Journal of Virology ◽

10.1128/jvi.00070-21 ◽

2021 ◽

Author(s):

Elliott S. Chiu ◽

Coby A. McDonald ◽

Sue VandeWoude

Keyword(s):

Mononuclear Cells ◽

Cell Function ◽

Leukemia Virus ◽

Endogenous Retroviruses ◽

Domestic Cat ◽

Feline Leukemia Virus ◽

Infectious Agents ◽

Biological Functions ◽

Peripheral Blood Mononuclear ◽

Solo Ltrs

Endogenous retroviruses (ERVs) are increasingly recognized for biological impacts on host cell function and susceptibility to infectious agents, particularly in relation to interactions with exogenous retroviral progenitors (XRVs). ERVs can simultaneously promote and restrict XRV infections using mechanisms that are virus- and host-specific. The majority of endogenous-exogenous retroviral interactions have been evaluated in experimental mouse or chicken systems which are limited in their ability to extend findings to naturally infected outbred animals. Feline leukemia virus (FeLV) has a relatively well-characterized endogenous retrovirus with a coexisting virulent exogenous counterpart and is endemic worldwide in domestic cats. We have previously documented an association between endogenous FeLV LTR copy number and abrogated exogenous FeLV in naturally infected cats and experimental infections in tissue culture. Analyses described here examine limited FeLV replication in experimentally infected peripheral blood mononuclear cells which correlates with higher enFeLV transcripts in these cells compared to fibroblasts. We further examine NCBI Sequence Read Archive RNA transcripts to evaluate enFeLV transcripts and RNA interference precursors. We find that lymphoid-derived tissues, which are experimentally less permissive to exogenous FeLV infection, transcribe higher levels of enFeLV under basal conditions. Transcription of enFeLV-LTR segments is significantly greater than other enFeLV genes. We documented transcription of a 21-nt miRNA just 3’ to the enFeLV 5’-LTR in the feline miRNAome of all datasets evaluated (n=27). Our findings point to important biological functions of enFeLV transcription linked to solo LTRs distributed within the domestic cat genome, with potential impacts on domestic cat exogenous FeLV susceptibility and pathogenesis. Importance Endogenous retroviruses (ERVs) are increasingly implicated in host cellular processes and susceptibility to infectious agents, specifically regarding interactions with exogenous retroviral progenitors (XRVs). Exogenous feline leukemia virus (FeLV) and its endogenous counterpart (enFeLV) represent a well characterized, naturally occurring XRV-ERV dyad. We have previously documented an abrogated FeLV infection in both naturally infected cats and experimental fibroblast infections that harbor higher enFeLV proviral loads. Using an in silico approach, we provide evidence of miRNA-transcription that are produced in tissues most important for FeLV infection, replication, and transmission. Our findings point to important biological functions of enFeLV transcription linked to solo-LTRs distributed within the feline genome, with potential impacts on domestic cat exogenous FeLV susceptibility and pathogenesis. This body of work provides additional evidence of RNAi as a mechanism of viral interference and is a demonstration of ERV exaptation by the host to defend against related XRVs.

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Infectious Endogenous Retroviruses in Cats and Emergence of Recombinant Viruses

Journal of Virology ◽

10.1128/jvi.00280-12 ◽

2012 ◽

Vol 86 (16) ◽

pp. 8634-8644 ◽

Cited By ~ 36

Author(s):

Yukari Anai ◽

Haruyo Ochi ◽

Shinya Watanabe ◽

So Nakagawa ◽

Maki Kawamura ◽

...

Keyword(s):

Leukemia Virus ◽

Endogenous Retroviruses ◽

Domestic Cat ◽

Feline Leukemia Virus ◽

Polymorphism Analysis ◽

Domestic Cats ◽

Heterozygous Locus ◽

Recombinant Viruses ◽

Genomic Insertions ◽

Insertional Polymorphism

Endogenous retroviruses (ERVs) comprise a significant percentage of the mammalian genome, and it is poorly understood whether they will remain as inactive genomes or emerge as infectious retroviruses. Although several types of ERVs are present in domestic cats, infectious ERVs have not been demonstrated. Here, we report a previously uncharacterized class of endogenous gammaretroviruses, termed ERV-DCs, that is present and hereditary in the domestic cat genome. We have characterized a subset of ERV-DC proviral clones, which are numbered according to their genomic insertions. One of these, ERV-DC10, located in the q12-q21 region on chromosome C1, is an infectious gammaretrovirus capable of infecting a broad range of cells, including human. Our studies indicate that ERV-DC10 entered the genome of domestic cats in the recent past and appeared to translocate to or reintegrate at a distinct locus as infectious ERV-DC18. Insertional polymorphism analysis revealed that 92 of 244 domestic cats had ERV-DC10 on a homozygous or heterozygous locus. ERV-DC-like sequences were found in primate and rodent genomes, suggesting that these ERVs, and recombinant viruses such as RD-114 and BaEV, originated from an ancestor of ERV-DC. We also found that a novel recombinant virus, feline leukemia virus subgroup D (FeLV-D), was generated by ERV-DCenvtransduction into feline leukemia virus in domestic cats. Our results indicate that ERV-DCs behave as donors and/or acceptors in the generation of infectious, recombinant viruses. The presence of such infectious endogenous retroviruses, which could be harmful or beneficial to the host, may affect veterinary medicine and public health.

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