In vivo evolution and selection of recombinant feline leukemia virus species

Bechtel, Marta K.; Mathes, Lawrence E.; Hayes, Kathleen; Phipps, Andrew J.; Roy-Burman, Pradip

doi:10.1016/s0168-1702(98)00015-x

Cited by 10 publications

(14 citation statements)

References 33 publications

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“…Interestingly, many of those changes were conserved in the natural FeLV-B isolates. Previously, 19 such nucleotide changes were identified, and 13 of them led to amino acid changes (2,3). Due to the design of the PCR primers employed in those earlier studies, all changes uncovered were restricted to the SU region.…”

Section: Vol 75 2001mentioning

confidence: 99%

“…3Ј recombination crossover sites and the presence or absence of the IRES-GFP transgene in these recombinants are indicated. (C) Representation of the identified 3Ј crossover sites for the recombinant species relative to the regions on the viral genome and relative to previously reported A-G crossover sites (2,3,21). The arrow indicates the 3Ј UTR of env.…”

mentioning

confidence: 99%

“…Evidence suggests that FeLV-B, and perhaps FeLV-C, species are formed by recombination in SU gene sequences between FeLV-A and endogenous FeLV (enFeLV) elements inherited in the domestic cat genome (2,3,6,10,13,14,16,(20)(21)(22). The pathogenicity of FeLV-A Rickard strain (FRA) was demonstrated by direct intradermal inoculation of plasmid DNA (pFRA) in neonatal cats (3,14).…”

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confidence: 99%

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A Replication-Competent Feline Leukemia Virus, Subgroup A (FeLV-A), Tagged with Green Fluorescent Protein Reporter Exhibits In Vitro Biological Properties Similar to Those of the Parental FeLV-A

Chang¹,

Pan²,

Logg

et al. 2001

J Virol

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We previously established that lymphoid tumors could be induced in cats by intradermal injection of ecotropic feline leukemia virus (FeLV), subgroup A, plasmid DNA. In preparation for in vivo experiments to study the cell-to-cell pathway for the spread of the virus from the site of inoculation, the green fluorescent protein (GFP) transgene fused to an internal ribosome entry site (IRES) was inserted after the last nucleotide of the env gene in the ecotropic FeLV-A Rickard (FRA) provirus. The engineered plasmid was transfected into feline fibroblast cells for production of viruses and determination of GFP expression. The virions produced were highly infectious, and the infected cells could continue to mediate strong expression of GFP after long-term propagation in culture. Similar to parental virus, the transgene-containing ecotropic virus demonstrated recombinogenic activity with endogenous FeLV sequences in feline cells to produce polytropic recombinant FeLV subgroup B-like viruses which also contained the IRES-GFP transgene in the majority of recombinants. To date, the engineered virus has been propagated in cell culture for up to 8 months without diminished GFP expression. This is the first report of a replication-competent FeLV vector with high-level and stable expression of a transgene.

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Section: Vol 75 2001mentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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A Replication-Competent Feline Leukemia Virus, Subgroup A (FeLV-A), Tagged with Green Fluorescent Protein Reporter Exhibits In Vitro Biological Properties Similar to Those of the Parental FeLV-A

Chang¹,

Pan²,

Logg

et al. 2001

J Virol

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“…There is solid evidence to indicate that interactions between infectious FeLV and non-infectious inherited endogenous FeLV elements generate recombinant viral quasispecies which represent a variety of chimeric envelope glycoproteins depending on the extent of amino terminal portion replaced by the endogenous env sequences (9,13,24). The viral species with specific adaptive amino acid mutations and with certain sites of recombination are rapidly selected for replication efficiency and are overrepresented at later time points after infection (2,3,14). FeLVs with recombinant env genes are detected with high frequency in naturally as well as experimentally induced feline lymphosarcomas (2,3,10,14,23,25).…”

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confidence: 99%

“…The viral species with specific adaptive amino acid mutations and with certain sites of recombination are rapidly selected for replication efficiency and are overrepresented at later time points after infection (2,3,14). FeLVs with recombinant env genes are detected with high frequency in naturally as well as experimentally induced feline lymphosarcomas (2,3,10,14,23,25). Evidence also exists to suggest that some defective env genes detected in FeLV-induced lymphosarcomas may be additional factors in the disease process (16,23).…”

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A Novel Truncated env Gene Isolated from a Feline Leukemia Virus-Induced Thymic Lymphosarcoma

Shi¹,

Roy-Burman

2000

J Virol

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We PCR amplified the exogenous feline leukemia virus (FeLV)-related env gene species from lymphosarcomas induced by intradermally administered plasmid DNA of either the prototype FeLV, subgroup A molecular clone, F6A, or a new molecular clone, FeLV-A, Rickard strain (FRA). Of the nine tumors examined, six showed the presence of deleted env species of variable sizes in the tumor DNA. One env mutant, which was detected in a FRA-induced thymic lymphosarcoma, had a large internal deletion beginning from almost the N-terminal surface glycoprotein (SU) up to the middle region of the transmembrane (TM) protein of the env gene. The deduced polypeptide of this truncated env (tenv) retained the complete signal peptide and seven amino acids of the N-terminal mature SU of FRA env gene, followed by eight amino acids from the frameshift in the TM region. To study the biological function of tenv, we used a murine retrovirus vector to produce amphotropic virions. Infection of feline fibroblasts (H927), human fibrosarcoma cells (HT1080), or human B-lymphoma cells (Raji) led to pronounced cytotoxicity, while the tenv virus did not induce significant cytotoxicity to feline T-lymphoma cells (3201B) or human T-lymphoma cells (CEM). Together, these results convincingly demonstrated that the genetic events that led to truncation in the env gene occurred de novo in FeLV lymphomagenesis and that such a product, tenv could induce cytotoxicity to fibroblastic and B-lymphoid cells but not to T-lymphoid tumor cells. This type of selective toxicity might be potentially important in the development of the neoplastic disease.Retroviruses are causative agents in the induction of lymphoid malignancies (leukemia-lymphoma complex) in mammals, including humans. In the domestic cat, an outbred species, which has the highest incidence of lymphoid malignancies of any animal, the disease is naturally associated with chronic feline leukemia virus (FeLV) infection (8, 18). There is solid evidence to indicate that interactions between infectious FeLV and non-infectious inherited endogenous FeLV elements generate recombinant viral quasispecies which represent a variety of chimeric envelope glycoproteins depending on the extent of amino terminal portion replaced by the endogenous env sequences (9,13,24). The viral species with specific adaptive amino acid mutations and with certain sites of recombination are rapidly selected for replication efficiency and are overrepresented at later time points after infection (2,3,14). FeLVs with recombinant env genes are detected with high frequency in naturally as well as experimentally induced feline lymphosarcomas (2,3,10,14,23,25). Evidence also exists to suggest that some defective env genes detected in FeLV-induced lymphosarcomas may be additional factors in the disease process (16,23).Although a previous study addressed the issue of in vivo derivation of defective env genes from an FeLV, subgroup A (FeLV-A) molecular clone (16), administration of an inoculum prepared by propagating the virus in feline cell culture...

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Inhibition of Feline Leukemia Virus Subgroup A Infection by Coinoculation with Subgroup B

et al. 2000

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Feline leukemia virus (FeLV) subgroup B arises de novo through recombination between the env genes of exogenous FeLV subgroup A and endogenous FeLV-like sequences. FeLV-B, which by itself is poorly infectious, will increase to high titer in the presence of FeLV-A, and is associated with FeLV-related neoplastic disease. Although the participation of FeLV-B in disease progression has not been definitively proven, circumstantial evidence supports the hypothesis that the generation of FeLV-B is linked to disease progression. The present study was designed to evaluate whether increasing the levels of FeLV-B early in FeLV-A infection could result in reduction of the incubation period for development of neoplastic disease. For this study, an isolate of FeLV-B, designated FeLV-1B3, was biologically cloned, partially sequenced, and subgroup typed. In in vivo studies, none of the neonatal cats inoculated with FeLV-1B3 alone converted to viremia positive, and all remained healthy throughout the observation period. All of the kittens inoculated with FeLV-A alone became chronically viremic, and those held for long-term observation all developed either neoplastic disease or anemia. However, kittens inoculated with the combination of FeLV-1B3 and FeLV-A showed attenuated infections whereby the majority of cats failed to develop chronic viremia. The apparent interference of FeLV-A infection by FeLV-B was time and titer dependent. This unexpected result suggests that FeLV-B may act as an attenuated virus, causing inhibition of FeLV-A possibly through an immune-mediated mechanism. Partial support for this view was provided by postmortem examination of cats inoculated with FeLV-1B3 alone. Even though none of these cats became viremic, FeLV antigen was detected as focal infections in select tissues, especially salivary gland epithelium, where enough antigen may be expressed to provide an immunizing dose against gag and pol cross-reacting antigens. This work may also provide another approach to vaccine development based on endogenous retrovirus vector systems.

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In vivo evolution and selection of recombinant feline leukemia virus species

Cited by 10 publications

References 33 publications

A Replication-Competent Feline Leukemia Virus, Subgroup A (FeLV-A), Tagged with Green Fluorescent Protein Reporter Exhibits In Vitro Biological Properties Similar to Those of the Parental FeLV-A

A Replication-Competent Feline Leukemia Virus, Subgroup A (FeLV-A), Tagged with Green Fluorescent Protein Reporter Exhibits In Vitro Biological Properties Similar to Those of the Parental FeLV-A

A Novel Truncated env Gene Isolated from a Feline Leukemia Virus-Induced Thymic Lymphosarcoma

Inhibition of Feline Leukemia Virus Subgroup A Infection by Coinoculation with Subgroup B

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