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The surface glycoprotein of feline leukemia virus isolate FeLV-945 is a determinant of altered pathogenesis in the presence or absence of the unique viral long terminal repeat.

ABSTRACT: Feline leukemia virus (FeLV) is a naturally transmitted gammaretrovirus that infects domestic cats. FeLV-945, the predominant isolate associated with non-T-cell disease in a natural cohort, is a member of FeLV subgroup A but differs in sequence from the FeLV-A prototype, FeLV-A/61E, in the surface glycoprotein (SU) and long terminal repeat (LTR). Substitution of the FeLV-945 LTR into FeLV-A/61E resulted in pathogenesis indistinguishable from that of FeLV-A/61E, namely, thymic lymphoma of T-cell origin. In contrast, substitution of both FeLV-945 LTR and SU into FeLV-A/61E resulted in multicentric lymphoma of non-T-cell origin. These results implicated the FeLV-945 SU as a determinant of pathogenic spectrum. The present study was undertaken to test the hypothesis that FeLV-945 SU can act in the absence of other unique sequence elements of FeLV-945 to determine the disease spectrum. Substitution of FeLV-A/61E SU with that of FeLV-945 altered the clinical presentation and resulted in tumors that demonstrated expression of CD45R in the presence or absence of CD3. Despite the evident expression of CD45R, a typical B-cell marker, T-cell receptor beta (TCR?) gene rearrangement indicated a T-cell origin. Tumor cells were detectable in bone marrow and blood at earlier times during the disease process, and the predominant SU genes from proviruses integrated in tumor DNA carried markers of genetic recombination. The findings demonstrate that FeLV-945 SU alters pathogenesis, although incompletely, in the absence of FeLV-945 LTR. Evidence demonstrates that FeLV-945 SU and LTR are required together to fully recapitulate the distinctive non-T-cell disease outcome seen in the natural cohort.

SUBMITTER: Bolin LL

PROVIDER: S-EPMC3807393 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature

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The surface glycoprotein of feline leukemia virus isolate FeLV-945 is a determinant of altered pathogenesis in the presence or absence of the unique viral long terminal repeat.

Bolin Lisa L LL Ahmad Shamim S Lobelle-Rich Patricia A PA Ooms Tara G TG Alvarez-Hernandez Xavier X Didier Peter J PJ Levy Laura S LS

Journal of virology 20130731 19

Feline leukemia virus (FeLV) is a naturally transmitted gammaretrovirus that infects domestic cats. FeLV-945, the predominant isolate associated with non-T-cell disease in a natural cohort, is a member of FeLV subgroup A but differs in sequence from the FeLV-A prototype, FeLV-A/61E, in the surface glycoprotein (SU) and long terminal repeat (LTR). Substitution of the FeLV-945 LTR into FeLV-A/61E resulted in pathogenesis indistinguishable from that of FeLV-A/61E, namely, thymic lymphoma of T-cell ...[more]

PMID: 23903838

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Project description: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 and 13 clones in 22 animals with FeLV-B to assess sequence diversity and recombination breakpoints. Our analysis revealed that FeLV-A sequences 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, although 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 individuals. This work represents a comprehensive analysis of endogenous-exogenous retroviral interactions with important insights into host-virus 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.

Project description:Feline calicivirus (FCV) is a common virus, found worldwide, mainly responsible for chronic ulceroproliferative faucitis and periodontitis. This virus has a high mutation rate, leading to the presence of numerous FCV strains in the field. The objectives of this study was to evaluate and compare the efficacy of two vaccines (Leucofeligen™ FeLV/RCP and Purevax™ RCP FeLV), which differ by their nature (live vs. inactivated) and the vaccinal strains, against circulating FCV strains. Thirty 9-week-old specific pathogen free (SPF) kittens were thus randomised into 3 groups and were either not vaccinated (control) or vaccinated (2 injections, 3 weeks apart) with one of the vaccines. Four weeks after the second injection of primary vaccination, the cats were inoculated with a pathogenic strain representative of the ones circulating in Europe (FCV-FR4_01) and followed for 2 weeks.After challenge, significant differences (p < 0.05) between control cats and cats vaccinated with Leucofeligen™ FeLV/RCP or Purevax™ RCP FeLV were observed for body weight variation, rectal temperature rise and maximum clinical scores, reflecting the intensity of the signs (83% and 67% lower in the respective vaccinated groups than in the control group). Significant differences were observed between the vaccinated groups, as cats vaccinated with Leucofeligen™ FeLV/RCP had a lower temperature rise (p < 0.05 at days post-challenge 3 to 5) and lower virus shedding titres (p < 0.05 at days post-challenge 8, 9 and 11) than cats vaccinated with Purevax™ RCP FeLV. Finally, only cats vaccinated with Leucofeligen™ FeLV/RCP had a significantly lower cumulative score, reflecting the intensity and duration of calicivirosis clinical signs, than the control cats (77% lower vs. 62% lower for cats vaccinated with Purevax™ RCP FeLV).Both vaccines, Leucofeligen™ FeLV/RCP and Purevax™ RCP FeLV, were found to be efficacious in reducing clinical signs induced by FCV-FR4_01, a FCV strain representative of the circulating ones. However, cats vaccinated with Leucofeligen™ FeLV/RCP were able to control the infection more efficiently than those vaccinated with Purevax™ RCP FeLV, as evidenced by the shorter duration of clinical signs and lower viral titre in excretions.

Dataset Information

The surface glycoprotein of feline leukemia virus isolate FeLV-945 is a determinant of altered pathogenesis in the presence or absence of the unique viral long terminal repeat.

Publications

The surface glycoprotein of feline leukemia virus isolate FeLV-945 is a determinant of altered pathogenesis in the presence or absence of the unique viral long terminal repeat.

Similar Datasets

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