Nucleotide sequence of AKV murine leukemia virus

Abstract

AKV is an endogenous, ecotropic murine leukemia virus that serves as one of the parents of the recombinant, oncogenic mink cell focus-forming viruses that arise in preleukemic AKR mice. I report the 8,374-nucleotide-long sequence of AKV, as determined from the infectious molecular clone AKR-623. The 5'-leader sequence of AKV extends to nucleotide 639, after which lies a long open reading frame encoding the gag and pol gene products. The reading frame is interrupted by a single amber codon separating the gag and pol genes. The pol gene overlaps the env gene within the 3' region of the AKV genome. The nucleotide sequence of the 5' region of AKV reveals the following features. (i) The 5'-leader sequence lacks any AUG codon to initiate translation of gPr8QW'-, suggesting that gPr8Yg'l is not required for the replication of AKV. (ii) A short portion of the leader region diverges in sequence from the closely related Moloney murine leukemia virus and appears to be related to a sequence highly repeated in eucaryotic genomes. (iii) As in Moloney murine leukemia virus, there is a potential RNA secondary structure flanking the amber codon that separates the gag and pol genes. This structure might function as a regulatory protein binding site that controls the relative levels of synthesis of the gag and pol precursors. The nucleotide sequence of the 3' region of AKV is compared with sequences reported previously from both infectious and noninfectious molecular clones of AKV.The murine leukemia virus (MLV) AKV resides in the germ line of AKR mice and is implicated in the high incidence of thymic leukemias that arise when these mice are 6 to 9 months old. AKV is expressed in AKR mice from birth (41) and is distinguished from the other MLV endogenous to AKR mice because it is ecotropic; i.e., it can infect mouse cells. Low-leukemic strains of mice (e.g., NIH/Swiss) which have acquired a germ line AKV provirus from AKR mice become viremic and subsequently contract leukemia, albeit with a considerably longer latency period (39,40). Nevertheless, AKV itself does not appear to be directly oncogenic because it is unable to induce leukemia in healthy mice (18,29).During the development of AKR mice, AKV recombines with germ line nonecotropic MLV to produce recombinant MLVs (4,5,9,17,19,23,38) not found in the germ line of AKR mice (3,17,36). The recombinants, called MCF, appear in the preleukemic thymus (14) and are thought to be the proximal oncogenic agent in AKR leukemogenesis because they can accelerate the onset of leukemia if injected into young AKR mice (6, 31), and they are found integrated in the genomes of leukemic thymocytes (3,16,36). Because the nonecotropic parent of MCF viruses has not been identified, the nonecotropic sequences within MCF genomes have been localized by comparison to AKV.The nucleotide sequence of the 3' region of the AKV genome has been reported previously. Lenz et al. (21) and Van Beveren et al. (56) determined the nucleotide sequence of the envelope (env) gene and the long terminal repeat (LTR), res...

cis acting RNA sequences control the gag-pol translation readthrough in murine leukemia virus

“…DNA sequence analysis of M-MuLV and the related AKV and FeLV revealed a putative secondary structure flanking the gag-pal amber codon (Shinnick et al, 1981;Herr, 1984;Laprevotte et al, 1984; Fig. 2A).…”

The adhesive and neurite-promoting molecule p30: analysis of the amino-terminal sequence and production of antipeptide antibodies that detect p30 at the surface of neuroblastoma cells and of brain neurons.

“…Thus, this sequence is not found in a computer homology search (DNASIS of LKB containing the sequences of Protein Identification Resource, data base R 12.0, dated March 1987). The most clearcut similarity.is found in a viral nucleoprotein (Herr, 1984) that has the same Six-amino acid sequence (Pro-Lys-Lys-Pro-Arg-Gly), but is otherwise a clearly different protein as compared to p30.…”

Characterization of gP85gag as an antigen recognized by Moloney leukemia virus-specific cytolytic T cell clones that function in vivo.

“…The two primary gag gene products, gPr80 gag and Pr65, are synthesized independently, gPr80 gag contains all Pr65 peptides as well as 4-6 kilodaltons of unique amino-terminal peptides (11,12). Several viruses, derived from or highly related to M-MLV, do not synthesize proteins related to M-MLV gPr80 gag (38,39). Since M-MLV only codes for Pr65 (40), the target molecule recognized by the virus-specific CTL clones must be encoded exclusively by the M-MLV genome.…”