Evidence for a new form of retroviral env transcript in leukemic and normal mouse lymphoid cells

Abstract

Murine leukemia virus-related RNA species were examined in a set of radiation-induced T-cell leukemias from BALB/c mice. No evidence was found for linkage of viral long terminal repeat-derived (U5) sequences to information of host origin. A novel class of 2-kilobase (kb) env-related transcripts, about 1 kb shorter than normal viral env messenger, was found in all the leukemias. All of the 2-kb transcripts contained sequences homologous to the xenotropic virus-related env sequences in the Friend spleen focus-forming virus, representing the N-terminal portion of gp7O. In two of the leukemias, these transcripts were found to contain both ecotropic plSE and U3 sequences in addition to the xenotropic gp7O-related sequence. These two leukemias, but not others in which ecotropic sequences were absent from the 2-kb RNA, harbored several copies of a specific class of env recombinant proviruses. These proviruses possessed full-size env genes and were submethylated, as shown by SmaI and XmaI digests of proviral DNA. Low levels of 2-kb RNA were found in normal thymocytes from strains BALB/c, AKR, and 129 but not from congenic 129 Glxmice. It is possible that the 2-kb RNA may originate by a novel splicing step that removes portions of the gp7O and plSE sequences from full-length env transcripts.

Multistage carcinogenesis involves multiple genes and multiple mechanisms

“…In the transformed fibroblasts we detected a prominent 24s RNA transcript homologous to an env probe. It is of interest that radiation-induced murine T-cell lymphomas also express endogenous env genes in the absence of production of infectious virus (Fischinger et al, 1982;Boccara et al, 1983). It appears that the 20s and 18s transcripts we detected in the transformed C3H 10T1/2 cells may reflect the expression of nonvirally related host sequences that utilize the LTR sequences as promoters.…”

Early clonality and high-frequency proviral integration into the c-myc locus in AKR leukemias

“…(C) Digestion with SmaI. Lane is seen also in DNA of control thymus and is derived from replicating germ line ecotropic proviruses in AKR/J mice (1,2).…”

Characterization of human endogenous retroviral envelope RNA transcripts

“…Studies of MuLV envelope (env) mRNA in normal mouse tissues have confirmed the presence of a 3.0-kilobase (kb) mRNA that comigrates with the 21S spliced long terminal repeat (LTR)-env mRNA transcribed in MuLV-infected cells (18). In addition to this endogenous 21S env mRNA, several other MuLV env-containing mRNAs have been identified in normal mouse tissues, including a smaller 1.8to 2.0-kb LTR-and env-hybridizing mRNA (3,18).…”

“…Restriction endonucleases (Bethesda Research Laboratories, Boehringer Mannheim Biochemicals, New England Biolabs, Inc.) were used as described in the recommendations of the manufacturers. Nucleotide sequences were determined by the chemical degradation method of Maxam and Gilbert (24), using isolated restriction enzyme fragments end labeled ([-y-32P]ATP, 3,000 Ci/mmol; Amersham) with T4 polynucleotide kinase (P-L Biochemicals). The cDNA insert of pPL1 was sequenced on both strands.…”

“…If one or more of these contain a completely open reading frame, its transcription and translation could produce a human env protein. It is of interest that a 1.8to 2.0-kb MuLV env mRNA has been identified in normal mouse tissue (3,18). This RNA apparently possesses a structure similar to that observed for the human 1.7-kb RNA: it hybridizes to 5' gp7O and LTR probes but appears to be deleted in 3' gp7O and transmembrane-anchor pl5E sequences.…”