Transduction of endogenous envelope genes by feline leukaemia virus in vitro

Abstract

Feline leukaemia viruses (FeLV) are exogenous retroviruses that can be detected in most cats with leukaemia, aplastic anaemia, myeloproliferative diseases and fatal immunosuppression. FeLV isolates have been divided into three subgroups, based on the viral envelope-determined properties of interference and host range in vitro. FeLV-A is present in all natural isolates and is generally minimally pathogenic. FeLV-B is found with FeLV-A in isolates from approximately 40% of natural infections and in a higher percentage of cats with lymphoma. Following the fundamental observations of genetic reassortment of avian retroviruses with endogenous viral genes and the origination of lymphomagenic viruses during the ontogeny of AKR mice, we show here that transfection of feline cells with FeLV-A DNA results in its recombination with endogenous FeLV-related sequences to produce viruses with the structural and host range properties of FeLV-B. Thus in vitro propagation of a retrovirus may result in the generation of variants with very different properties.

Feline Leukemia Virus Envelope Sequences That Affect T-Cell Tropism and Syncytium Formation Are Not Part of Known Receptor-Binding Domains

“…Like the 81T-109 envelope clone, the subclones encoding the 81T-3 and 81T-6 envelope were generated from PCRamplified envelope gene fragments obtained from the tumor of cat 40681; these clones were described previously (31). To construct the EE(ET)E chimeras, a 0.9-kb gel-purified MamI-RsrII fragment encompassing the 3Ј half of the envelope gene of 81T-3 and 81T-6, including coding sequences for the C-terminal half of SU and all of TM, was cloned into a similarly digested 3Ј subclone of 61E (called 3ЈEE [28]). Clones with the correct chimeric structure were identified by restriction enzyme digestion and nucleotide sequence analysis.…”

Molecular cloning and characterization of a defective recombinant feline leukaemia virus associated with myeloid leukaemia

“…For subgroup B viruses, inoculation of these alone has induced long latency thymic lymphosarcomas in isolated cases (O. Jarrett, personal communication) and such viruses are more commonly present in diseased rather than healthy viraemic cats . FeLV-B viruses appear to arise by recombination of FeLV-A with endogenous FeLV-related sequences (enFeLV) that harbour FeLV-B-like env genes (Stewart et al, 1986;Overbaugh et al, 1988a). In this and many other respects FeLV-B viruses provide a close parallel to mink-cell focus-forming (MCF) viruses of the mouse (Elder & Mullins, 1983;Nell et al, 1987).…”

Differential Diagnosis of Feline Leukemia Virus Subgroups Using Pseudotype Viruses Expressing Green Fluorescent Protein

“…FeLV-A is considered to be less pathogenic than other subgroups [12]. FeLV-B induces leukemia in a relatively short period and FeLV-C induces severe anemia [12,13,15]. Each subgroup utilizes a distinct receptor and interferes with the same subgroup in the cells, i.e., FeLV can not infect cells previously infected with the same subgroup [7,11].…”

“…To prepare stock viruses of FeLV subgroups A, B and C, we transfected infectious molecular clones of FeLV into HEK 293T cells to avoid recombination with the endogenous FeLV genome present in feline cells [13]. One microgram each of infectious molecular clones of FeLV-A, B and C, named pFGA-5 [19], pGAHF [19] and pFSC [15], respectively, was transfected twice into HEK293T cells using FuGENE6 (Roche Diagnostics GmbH, Mannheim, Germany).…”