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Evolution of feline leukemia virus variant genomes with insertions, deletions, and defective envelope genes in infected cats with tumors.

ABSTRACT: In order to study retroviral variation, selection, and viral correlates of in vivo pathogenicity, we documented the evolution of feline leukemia virus (FeLV) variants in cats that died with thymic lymphoma after infection with molecularly cloned subgroup A FeLV. Using genomic DNA from cat necropsy samples, we employed PCR to amplify and clone the envelope gene, which is a major determinant of the specific pathogenicity of different FeLV variants. In the envelope gene, mutations encoded scattered amino acid changes that did not cluster into clearly definable variable regions; however, characterization of these terminal variant sequences revealed a predominance of G-to-A and A-to-G nucleotide substitutions. Additionally, some cats harbored variants with recombinant subgroup B-like envelope genes, while the major variant from one cat had a 12-bp insertion in a region previously characterized as an immunodeficiency-inducing determinant. Finally, proviruses from tumor DNA frequently possessed envelope genes predicted to encode a protein truncated in the N-terminal half because of either premature termination codons or deletions ranging from 29 to 1,666 bp. In contrast, all envelope genes cloned from the bone marrow of one cat were predicted to encode full-length envelope product, and only a minority of proviral clones from a cat that did not develop a tumor had defective envelope genes. Thus, in the cat, viruses evolved from subgroup A FeLV that had point mutations, insertions, deletions, or recombinant envelope genes. Furthermore, defective variants were particularly prominent in T-cell tumors.

SUBMITTER: Rohn JL

PROVIDER: S-EPMC236723 | biostudies-other | 1994 Apr

REPOSITORIES: biostudies-other

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Evolution of feline leukemia virus variant genomes with insertions, deletions, and defective envelope genes in infected cats with tumors.

Rohn J L JL Linenberger M L ML Hoover E A EA Overbaugh J J

Journal of virology 19940401 4

In order to study retroviral variation, selection, and viral correlates of in vivo pathogenicity, we documented the evolution of feline leukemia virus (FeLV) variants in cats that died with thymic lymphoma after infection with molecularly cloned subgroup A FeLV. Using genomic DNA from cat necropsy samples, we employed PCR to amplify and clone the envelope gene, which is a major determinant of the specific pathogenicity of different FeLV variants. In the envelope gene, mutations encoded scattered ...[more]

PMID: 8139030

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Project description:Approximately 5% of cats in animal shelters in the United States test positive for either feline leukemia virus (FeLV) or feline immunodeficiency virus (FIV), which translates to more than 100,000 positive cats managed by shelters each year. Little is known about the current status of retroviral management in animal shelters, particularly in regions burdened by chronic pet overpopulation and high shelter admissions, such as the southern United States. The purpose of this study was to describe feline retroviral management in Florida shelters. Shelters were surveyed on practices including selection of cats for testing, diagnostic techniques, and outcome options for cats with positive test results. Responses were received from 139 of 153 animal shelters known to admit cats, including 55 municipal shelters (40%), 70 private shelters (50%), and 14 private shelters with municipal contracts (10%). A total of 115 shelters (83%) performed at least some testing, most using combination point-of-care devices for simultaneous FeLV antigen and FIV antibody screening. Of shelters that performed any testing, 56 (49%) tested all cats for FeLV and 52 (45%) tested all cats for both FeLV and FIV. The most common reason for testing was screening adoptable cats (108 shelters; 94%) and cats available for transfer to other organizations (78; 68%). Testing cats in trap-neuter-return/return-to-field programs was least common (21; 18%). Most common outcome options for positive cats included adoption (74; 64%), transfer (62; 54%), and euthanasia (49; 43%). Euthanasia following a positive test result was more common for cats with FeLV (49; 43%) than for cats with FIV (29; 25%) and was more common in municipal shelters, rural shelters, shelters taking in <500 cats a year, and shelters with overall live outcome rates for cats <70%. Although Florida shelter compliance with national guidelines for identification and management of FeLV and FIV positive cats was variable, most had live outcome options for at least some of their cats with positive test results. Increased access to training and practical programmatic tools may help more shelters implement cost-effective testing protocols, reduce risk for transmission to other cats, and support the best outcomes for this vulnerable population of cats.

Project description:BackgroundThere are two biotypes of feline coronavirus (FCoV): the self-limiting feline enteric coronavirus (FECV) and the feline infectious peritonitis virus (FIPV), which causes feline infectious peritonitis (FIP), a fatal disease associated with cats living in multi-cat environments. This study provides an insight on the various immune mediators detected in FCoV-positive cats which may be responsible for the development of FIP.ResultsIn this study, using real-time PCR and multiplex bead-based immunoassay, the expression profiles of several immune mediators were examined in Crandell-Reese feline kidney (CRFK) cells infected with the feline coronavirus (FCoV) strain FIPV 79-1146 and in samples obtained from FCoV-positive cats. CRFK cells infected with FIPV 79-1146 showed an increase in the expression of interferon-related genes and pro-inflammatory cytokines such as MX1, viperin, CXCL10, CCL8, RANTES, KC, MCP1, and IL8. In addition, an increase in the expression of the above cytokines as well as GM-CSF and IFNγ was also detected in the PBMC, serum, and peritoneal effusions of FCoV-positive cats. Although the expression of MX1 and viperin genes was variable between cats, the expression of these two genes was relatively higher in cats having peritoneal effusion compared to cats without clinically obvious effusion. Higher viral load was also detected in the supernatant of peritoneal effusions compared to in the plasma of FCoV-positive cats. As expected, the secretion of IL1β, IL6 and TNFα was readily detected in the supernatant of peritoneal effusions of the FCoV-positive cats.ConclusionsThis study has identified various pro-inflammatory cytokines and interferon-related genes such as MX1, viperin, CXCL10, CCL8, RANTES, KC, MCP1, IL8, GM-CSF and IFNγ in FCoV-positive cats. With the exception of MX1 and viperin, no distinct pattern of immune mediators was observed that distinguished between FCoV-positive cats with and without peritoneal effusion. Further studies based on definitive diagnosis of FIP need to be performed to confirm the clinical importance of this study.

Dataset Information

Evolution of feline leukemia virus variant genomes with insertions, deletions, and defective envelope genes in infected cats with tumors.

Publications

Evolution of feline leukemia virus variant genomes with insertions, deletions, and defective envelope genes in infected cats with tumors.

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