Localization of the leukemogenic determinants of SL3-3, an ecotropic, XC-positive murine leukemia virus of AKR mouse origin

Jack Lenz, W. A. Haseltine

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

SL3-3 is a potent leukemogenic retrovirus that closely resembles the nonleukemogenic virus Akv. Both viruses were isolated from AKR mice, have ecotropic host ranges, and form plaques in the XC assay. They differ at only 1 to 2% of the nucleotides in the viral genomes but differ markedly in virulence properties. SL3-3 induces leukemia in a high percentage of inoculated AKR, C3H, CBA, and NFS mice, whereas Akv does not induce disease in any of these strains. To determine which region of the genome accounts for the leukemogenic potential of SL3-3, we constructed recombinant genomes between molecular clones of SL3-3 and Akv. Recombinant, viral DNA genomes were cloned and then were transfected onto NIH 3T3 fibroblasts to generate infectious virus. The recombinant viruses were tested for leukemogenicity in AKR/J, CBA/J, and C3Hf/Bi mice. We localized the primary leukemogenic determinant to a 3.8-kilobase fragment of the SL3-3 genome containing the viral long terminal repeat, 5' untranslated sequences, gag gene, and 5', 30% of the pol gene. Reciprocal recombinants, containing the equivalent region from Akv, linked to the env gene and the remainder of the pol gene from SL3-3, did not induce leukemia. We conclude that the primary virulence determinant of SL3-3 lies outside the region of the genome that encodes the envelope proteins gp70 and p15E.

Original languageEnglish (US)
Pages (from-to)317-328
Number of pages12
JournalJournal of Virology
Volume47
Issue number2
StatePublished - 1983
Externally publishedYes

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Murine leukemia virus
Inbred AKR Mouse
Murine Leukemia Viruses
Viral Genome
pol Genes
Viruses
genome
mice
Genome
Virulence
viruses
Leukemia
gag Genes
env Genes
leukemia
Inbred CBA Mouse
Recombinant DNA
Terminal Repeat Sequences
Host Specificity
Viral DNA

ASJC Scopus subject areas

  • Immunology

Cite this

Localization of the leukemogenic determinants of SL3-3, an ecotropic, XC-positive murine leukemia virus of AKR mouse origin. / Lenz, Jack; Haseltine, W. A.

In: Journal of Virology, Vol. 47, No. 2, 1983, p. 317-328.

Research output: Contribution to journalArticle

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abstract = "SL3-3 is a potent leukemogenic retrovirus that closely resembles the nonleukemogenic virus Akv. Both viruses were isolated from AKR mice, have ecotropic host ranges, and form plaques in the XC assay. They differ at only 1 to 2{\%} of the nucleotides in the viral genomes but differ markedly in virulence properties. SL3-3 induces leukemia in a high percentage of inoculated AKR, C3H, CBA, and NFS mice, whereas Akv does not induce disease in any of these strains. To determine which region of the genome accounts for the leukemogenic potential of SL3-3, we constructed recombinant genomes between molecular clones of SL3-3 and Akv. Recombinant, viral DNA genomes were cloned and then were transfected onto NIH 3T3 fibroblasts to generate infectious virus. The recombinant viruses were tested for leukemogenicity in AKR/J, CBA/J, and C3Hf/Bi mice. We localized the primary leukemogenic determinant to a 3.8-kilobase fragment of the SL3-3 genome containing the viral long terminal repeat, 5' untranslated sequences, gag gene, and 5', 30{\%} of the pol gene. Reciprocal recombinants, containing the equivalent region from Akv, linked to the env gene and the remainder of the pol gene from SL3-3, did not induce leukemia. We conclude that the primary virulence determinant of SL3-3 lies outside the region of the genome that encodes the envelope proteins gp70 and p15E.",
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