Viral interference in feline leukemia-sarcoma complex

mentioning

confidence: 99%

Identification of Envelope Determinants of Feline Leukemia Virus Subgroup B That Permit Infection and Gene Transfer to Cells Expressing Human Pit1 or Pit2

Sugai

Eiden²,

Anderson

et al. 2001

“…While FeLV causes a wide range of neoplastic and cytosuppressive diseases, it is unclear if the diversity of disease is related to disease-specific variants of FeLV or to the genomic instability of the virus (17,29). FeLV is divided into three subgroups (A, B, and C) based on the apparent binding of the large external envelope glycoprotein gp70 to subgroup-specific receptors (13,32,33). The weakly pathogenic FeLV subgroup A (FeLV-A) is commonly transmitted in nature (9,10) but rarely leads to disease (5) until new subgroups, FeLV-B or FeLV-C, arise de novo as a result of recombination and/or mutation.…”

mentioning

confidence: 99%

Differential Pathogenicity of Two Feline Leukemia Virus Subgroup A Molecular Clones, pFRA and pF6A

Phipps¹,

Chen

Hayes³

et al. 2000

F6A, a molecular clone of subgroup A feline leukemia virus (FeLV) is considered to be highly infectious but weakly pathogenic. In recent studies with a closely related subgroup A molecular clone, FRA, we demonstrated high pathogenicity and a strong propensity to undergo recombination with endogenous FeLV (enFeLV), leading to a high frequency of transition from subgroup A to A/B. The present study was undertaken to identify mechanisms of FeLV pathogenesis that might become evident by comparing the two closely related molecular clones. F6A was shown to have an infectivity similar to that of FRA when delivered as a provirus. Virus load and antibody responses were also similar, although F6A-infected cats consistently carried higher virus loads than FRA-infected cats. However, F6A-infected cats were slower to undergo de novo recombination with enFeLV and showed slower progression to disease than FRA-infected cats. Tumors collected from nine pF6A-or pFRAinoculated cats expressed lymphocyte markers for T cells (seven tumors) and B cells (one tumor), and non-T/B cells (one tumor). One cat with an A-to-A/C conversion developed erythrocyte hypoplasia. Genomic mapping of recombinants from pF6A-and pFRA-inoculated cats revealed similar crossover sites, suggesting that the genomic makeup of the recombinants did not contribute to increased progression to neoplastic disease. From these studies, the mechanism most likely to account for the pathologic differences between F6A and FRA is the lower propensity for F6A to undergo de novo recombination with enFeLV in vivo. A lower recombination rate is predicted to slow the transition from subgroup A to A/B and slow the progression to disease.

“…Feline leukemia virus (FeLV) has been categorized into three subgroups (A, B, and C) by viral interference assays that identify genetic sequence variation in the viral surface glycoprotein (SU) moiety of the envelope (env) gene (17,18). 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).…”

mentioning

confidence: 99%

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

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.