scholarly journals Feline leukemia virus (FeLV) endogenous and exogenous recombination events result in multiple FeLV-B subtypes during natural infection

2021 ◽  
Author(s):  
Katelyn Erbeck ◽  
Roderick B. Gagne ◽  
Simona Kraberger ◽  
Elliott S. Chiu ◽  
Melody Roelke-Parker ◽  
...  
Keyword(s):  
Leukemia Virus ◽  
Natural Infection ◽  
Horizontal Transmission ◽  
Genetic Material ◽  
Feline Leukemia Virus ◽  
Natural Setting ◽  
Domestic Cats ◽  
Wide Range ◽  
Closed Colony ◽  
Recombination Breakpoints

Feline leukemia virus (FeLV) is associated with a range of clinical signs in felid species. Differences in disease processes are closely related to genetic variation in the envelope ( env ) region of the genome of six defined subgroups. The primary hosts of FeLV are domestic cats of the Felis genus that also harbor endogenous FeLV (enFeLV) elements stably integrated in their genomes. EnFeLV elements display 86% nucleotide identity to exogenous, horizontally transmitted FeLV (FeLV-A). Variation between enFeLV and FeLV-A is primarily in the long terminal repeat (LTR) and env regions, which potentiates generation of the FeLV-B recombinant subgroup during natural infection. The aim of this study was to examine recombination behavior of exogenous FeLV (exFeLV) and enFeLV in a natural FeLV epizootic. We previously described that of 65 individuals in a closed colony, 32 had productive FeLV-A infection, and 22 of these individuals had detectable circulating FeLV-B. We cloned and sequenced the env gene of FeLV-B, FeLV-A, and enFeLV spanning known recombination breakpoints and examined between 1-13 clones in 22 animals with FeLV-B to assess sequence diversity and recombination breakpoints. Our analysis revealed that FeLV-A circulating in the population, as well as enFeLV env sequences, are highly conserved. We documented many recombination breakpoints resulting in the production of unique FeLV-B genotypes. More than half of the cats harbored more than one FeLV-B variant, suggesting multiple recombination events between enFeLV and FeLV-A. We concluded that FeLV-B was predominantly generated de novo within each host, though we could not definitively rule out horizontal transmission, as nearly all cats harbored FeLV-B sequences that were genetically highly similar to those identified in other individual. This work represents a comprehensive analysis of endogenous-exogenous retroviral interactions with important insights into host-viral interactions that underlie disease pathogenesis in a natural setting. Importance Feline leukemia virus (FeLV) is a felid retrovirus with a variety of disease outcomes. Exogenous FeLV-A is the virus subgroup almost exclusively transmitted between cats. Recombination between FeLV-A and endogenous FeLV analogues in the cat genome may result in emergence of largely replication-defective, but highly virulent subgroups. FeLV-B is formed when the 3’ envelope ( env ) region of endogenous FeLV (enFeLV) recombines with that of the exogenous FeLV (exFeLV) during viral reverse transcription and integration. Both domestic cats and wild relatives of the Felis genus harbor enFeLV, which has been shown to limit FeLV-A disease outcome. However, enFeLV also contributes genetic material to the recombinant FeLV-B subgroup. This study evaluates endogenous-exogenous recombination outcomes in a naturally infected closed-colony of cats to determine mechanisms and risk of endogenous retroviral recombination during exogenous virus exposure that leads to enhanced virulence. While FeLV-A and enFeLV env regions were highly conserved from cat to cat, nearly all individuals with emergent FeLV-B had unique combinations of genotypes, representative of a wide range of recombination sites within env . The findings provide insight into unique recombination patterns for emergence of new pathogens and can be related to similar viruses across species.

scholarly journals Feline leukemia virus (FeLV) endogenous and exogenous recombination events result in multiple FeLV-B subtypes during natural infection

2021 ◽  
Author(s):  
Katelyn Erbeck ◽  
Roderick B. Gagne ◽  
Simona Kraberger ◽  
Elliott S. Chiu ◽  
Melody Roelke Parker ◽  
...  
Keyword(s):  
De Novo ◽  
Leukemia Virus ◽  
Natural Infection ◽  
Horizontal Transmission ◽  
Clinical Signs ◽  
Feline Leukemia Virus ◽  
Natural Setting ◽  
Domestic Cats ◽  
Closed Colony ◽  
Recombination Breakpoints

AbstractFeline leukemia virus (FeLV) is associated with a range of clinical signs in felid species. The primary hosts of FeLV are domestic cats of the Felis genus that also harbor endogenous FeLV (enFeLV) elements stably integrated in their genomes. EnFeLV elements display 86% nucleotide identity to exogenous, horizontally transmitted FeLV (FeLV-A). Variation between enFeLV and FeLV-A is primarily in the long terminal repeat (LTR) and env regions, which potentiates generation of FeLV-B recombinant subtypes during natural infection with enhanced virulence. The aim of this study was to examine exogenous FeLV (exFeLV) and enFeLV recombination events in a natural FeLV epizootic. We previously described that of 32 individuals in a closed colony with productive FeLV-A infection, 22 had detectable circulating FeLV-B. We cloned and sequenced the env gene of FeLV-B, FeLV-A, and enFeLV spanning known recombination breakpoints, examining between 1-13 clones per individual to assess sequence diversity and recombination sites. We documented multiple recombination breakpoints resulting in the production of unique FeLV-B genotypes. At least half of the cats harbored more than one FeLV-B variant, and almost all animals had variants similar to those recovered from at least one other individual in the colony. This analysis reveals that FeLV-B is predominantly generated de novo within each host, though horizontal transmission may be inferred based upon FeLV-B sequence identities between individuals. This work represents a comprehensive analysis of endogenous-exogenous retroviral interactions with important insights into host-viral interactions that underlie disease pathogenesis in a natural setting.ImportanceFeline leukemia virus (FeLV) is a felid retrovirus associated with a variety of disease outcomes. Exogenous FeLV-A is the most common horizontally transmitted virus subgroup. Domestic cats (Felis catus) harbor endogenous copies of FeLV (enFeLV) in their genomes. Recombination between FeLV-A and enFeLV may result in emergence of largely replication-defective, but highly virulent recombinant strains. FeLV-B, the most common recombinant form, results when enFeLV env recombines with FeLV-A during FeLV replication. This study evaluated endogenous-exogenous recombination outcomes in a naturally-infected closed colony of domestic cats to determine recombination sites and FeLV-B genotypic heterogeneity associated with enhanced disease virulence. While FeLV-A and enFeLV genotypes were highly conserved, a large number of unique FeLV-B variants were identified in association with predicted recombination hotspots. The findings provide insight into recombination events between viral and host genomes that result in new, and potentially more pathogenic, viral strains.

scholarly journals Ancestral Mutations Acquired in Refrex-1, a Restriction Factor against Feline Retroviruses, during its Cooption and Domestication

2015 ◽  
Vol 90 (3) ◽  
pp. 1470-1485 ◽  
Author(s):  
Jumpei Ito ◽  
Takuya Baba ◽  
Junna Kawasaki ◽  
Kazuo Nishigaki
Keyword(s):  
Field Model ◽  
Leukemia Virus ◽  
Endogenous Retroviruses ◽  
Chimeric Virus ◽  
Feline Leukemia Virus ◽  
Domestic Cats ◽  
Terminal Domain ◽  
Viral Particles ◽  
Triangular Relationships ◽  
Retroviral Infections

ABSTRACTEndogenous retroviruses (ERVs) are remnants of ancestral retroviral infections of germ cells. Retroviral endogenization is an adaptation process for the host genome, and ERVs are gradually attenuated or inactivated by mutation. However, some ERVs that have been “domesticated” by their hosts eventually gain physiological functions, such as placentation or viral resistance. We previously reported the discovery of Refrex-1, a soluble antiretroviral factor in domestic cats that specifically inhibits infection by feline leukemia virus subgroup D (FeLV-D), a chimeric virus of FeLV, and a feline ERV, ERV-DC. Refrex-1 is a truncated envelope protein (Env) encoded by both ERV-DC7 and ERV-DC16 proviral loci. Here, we reconstituted ancestral and functional Env from ERV-DC7 and ERV-DC16 envelope genes (env) by inducing reverse mutations. Unexpectedly, ERV-DC7 and ERV-DC16 full-length Env (ERV-DC7 fl and ERV-DC16 fl), reconstructed by removing stop codons, did not produce infectious viral particles. ERV-DC7 fl and ERV-DC16 fl were highly expressed in cells but were not cleaved into surface subunits (SU) and transmembrane subunits, nor were they incorporated into virions. G407R/N427I-A429T and Y431D substitutions within the SU C-terminal domain of ERV-DC7 fl and ERV-DC16 fl, respectively, caused these dysfunctions. The residues glycine 407 and tyrosine 431 are relatively conserved among infectious gammaretroviruses, and their substitution causes the same dysfunctions as the tested retroviruses. Our results reveal that specific mutations within the SU C-terminal domain suppressed Env cleavage and incorporation into virions and indicate that these mutations contributed to the domestication of Refrex-1 through multistep events that occurred in the postintegration period.IMPORTANCEDomestic cats are colonized with various exogenous retroviruses (exRVs), such as feline leukemia virus (FeLV), and their genomes contain numerous ERVs, some of which are replication-competent proviruses. The feline hosts, exRVs, and ERVs have complicated genetic interactions and provide an interesting field model for triangular relationships: recombination between FeLV and ERV-DC, which is a feline ERV, generated FeLV-D, a chimeric virus, and FeLV-D is restricted by Refrex-1, an antiretroviral factor corresponding to truncated Env of ERV-DC7 and ERV-DC16. Here, we reconstructed ancestral, functional Env from ERV-DC7 and ERV-DC16envby inducing reverse mutations to elucidate how Refrex-1 was generated from its ancestor. Our results reveal that they were repeatedly inactivated by mutations preventing Env maturation. Our results provide insights into how ERVs were “domesticated” by their hosts and identify the mutations that mediated these evolutions. Notably, experiments that restore inactivated ERVs might uncover previously unrecognized features or properties of retroviruses.

scholarly journals Epidemiologic survey of feline leukemia virus in domestic cats on Tsushima Island, Japan: management strategy for Tsushima leopard cats

2017 ◽  
Vol 29 (6) ◽  
pp. 889-895 ◽  
Author(s):  
Isaac Makundi ◽  
Yushi Koshida ◽  
Kyohei Kuse ◽  
Takahiro Hiratsuka ◽  
Jumpei Ito ◽  
...  
Keyword(s):  
Management Strategy ◽  
Leukemia Virus ◽  
Feline Leukemia Virus ◽  
Domestic Cats ◽  
Epidemiologic Survey

scholarly journals Molecular detection of viral agents in free-ranging and captive neotropical felids in Brazil

2017 ◽  
Vol 29 (5) ◽  
pp. 660-668 ◽  
Author(s):  
Mariana M. Furtado ◽  
Sueli A. Taniwaki ◽  
Iracema N. de Barros ◽  
Paulo E. Brandão ◽  
José L. Catão-Dias ◽  
...  
Keyword(s):  
Feline Immunodeficiency Virus ◽  
Molecular Detection ◽  
Puma Concolor ◽  
Leukemia Virus ◽  
Feline Leukemia Virus ◽  
Molecular Testing ◽  
Domestic Cats ◽  
Immunodeficiency Virus ◽  
Free Ranging ◽  
Feline Coronavirus

We describe molecular testing for felid alphaherpesvirus 1 (FHV-1), carnivore protoparvovirus 1 (CPPV-1), feline calicivirus (FCV), alphacoronavirus 1 (feline coronavirus [FCoV]), feline leukemia virus (FeLV), feline immunodeficiency virus (FIV), and canine distemper virus (CDV) in whole blood samples of 109 free-ranging and 68 captive neotropical felids from Brazil. Samples from 2 jaguars ( Panthera onca) and 1 oncilla ( Leopardus tigrinus) were positive for FHV-1; 2 jaguars, 1 puma ( Puma concolor), and 1 jaguarundi ( Herpairulus yagouaroundi) tested positive for CPPV-1; and 1 puma was positive for FIV. Based on comparison of 103 nucleotides of the UL24-UL25 gene, the FHV-1 sequences were 99–100% similar to the FHV-1 strain of domestic cats. Nucleotide sequences of CPPV-1 were closely related to sequences detected in other wild carnivores, comparing 294 nucleotides of the VP1 gene. The FIV nucleotide sequence detected in the free-ranging puma, based on comparison of 444 nucleotides of the pol gene, grouped with other lentiviruses described in pumas, and had 82.4% identity with a free-ranging puma from Yellowstone Park and 79.5% with a captive puma from Brazil. Our data document the circulation of FHV-1, CPPV-1, and FIV in neotropical felids in Brazil.

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

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.

Infection strategies of retroviruses and social grouping of domestic cats

1997 ◽  
Vol 75 (12) ◽  
pp. 1994-2002 ◽  
Author(s):  
Emmanuelle Fromont ◽  
Franck Courchamp ◽  
Dominique Pontier ◽  
Marc Artois
Keyword(s):  
Selective Pressure ◽  
Leukemia Virus ◽  
Host Population ◽  
Feline Leukemia Virus ◽  
Domestic Cats ◽  
Worldwide Distribution ◽  
Transmission Modes ◽  
Social Grouping ◽  
Low Prevalence ◽  
The Impact

It is thought that parasites may exert selective pressure on the social structure of host populations. We compared the impact of feline immunodeficiency virus (FIV) and feline leukemia virus (FeLV), two retroviruses commonly found in domestic cats (Felis catus). Because of low transmissibility and virulence, both infections have a worldwide distribution and low prevalence. Transmission modes differ: FIV is transmitted only through biting, while FeLV transmission occurs by biting, licking, grooming, and sharing food and from mother to fetus. FeLV is also more pathogenic than FIV. We compared FIV and FeLV prevalence and risk factors within five populations of cats. FIV infection occurred almost exclusively among adult male cats fighting to acquire and maintain dominant status. Classes at risk for FeLV infection included sexually intact cats allowed to roam freely. The impact of FeLV on host population growth was greater than that of FIV but varied among populations. Our results show that FIV is favoured by individual aggressiveness and a hierarchical social system, while FeLV is more prevalent among socially active cats. FeLV may constitute a source of selective pressure against numerous amicable contacts, particularly in urban cat populations, where aggression among individuals is reduced.

Prevalence of feline leukemia virus infection in domestic cats in Rio de Janeiro

2012 ◽  
Vol 14 (8) ◽  
pp. 583-586 ◽  
Author(s):  
Nadia R de Almeida ◽  
Maria G M Danelli ◽  
Lucia H P da Silva ◽  
Mitika K Hagiwara ◽  
Carlos Mazur
Keyword(s):  
Virus Infection ◽  
Rio De Janeiro ◽  
Leukemia Virus ◽  
Feline Leukemia Virus ◽  
Domestic Cats

scholarly journals Serological and molecular investigation of Leishmania spp. infection in cats from an area endemic for canine and human leishmaniasis in Northeast Brazil

2019 ◽  
Vol 28 (4) ◽  
pp. 790-796 ◽  
Author(s):  
José Artur Brilhante Bezerra ◽  
Ilanna Vanessa Pristo de Medeiros Oliveira ◽  
Ana Carolina Yamakawa ◽  
Mariana Guimarães Nilsson ◽  
Klívio Loreno Raulino Tomaz ◽  
...  
Keyword(s):  
Risk Factors ◽  
Leukemia Virus ◽  
Genetic Material ◽  
Clinical Signs ◽  
Rio Grande ◽  
Feline Leukemia Virus ◽  
Pcr Analysis ◽  
Blood Samples ◽  
Human Leishmaniasis ◽  
Leishmania Spp

Abstract The aim of this study was to investigate the occurrence of Leishmania spp. antibodies, and its association with feline immunodeficiency virus (FIV) and feline leukemia virus (FeLV), in domestic cats from an area endemic for canine and human leishmaniasis in Rio Grande do Norte State, Brazil. Ninety-one cats were subjected to a complete clinical exam, and blood samples were collected. An epidemiological questionnaire was used to investigate the risk factors. IgG anti-Leishmania spp. antibodies were detected by immunofluorescence antibody test (IFAT), with a cut-off value of 1:40. Polymerase chain reaction (PCR) was performed to detect genetic material of Leishmania spp. in the blood samples. The presence of antibodies against FIV and antigens of FeLV was evaluated using an immunochromatographic test. Seropositivity for Leishmania spp., FIV, and FeLV was observed in 14/91 (15.38%), 26/91 (28.57%), and 3/91 (3.29%) cats, respectively. All samples gave negative results on PCR analysis. Based on these data, no significant statistical association was observed between seropositivity for Leishmania spp., and sex, age, presence of clinical signs, evaluated risk factors, and positivity for retroviruses. These findings demonstrated for the first time that cats from Mossoró, Rio Grande do Norte, are being exposed to this zoonosis and might be part of the epidemiological chain of transmission of visceral leishmaniasis.

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