Variation in Avian Retrovirus Genomes*

Coffin, John M.; Tsichlis, Philip N.; Barker, Christopher S.; Voynow, S L; Robinson, Harriet L.

doi:10.1111/j.1749-6632.1980.tb27982.x

Cited by 64 publications

(36 citation statements)

References 38 publications

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“…These error frequencies are high relative to those of DNA polymerases that are capable of proofreading, such as E. coli DNA polymerase I (4), E. coli DNA polymerase III (36), T4 DNA polymerase (19), chicken polymerase -y (35), and calf polymerase 8 (5,32). The base substitution fidelity of exonuclease-deficient cellular DNA polymerases varies over a 6,000-fold range and depends not only on the polymerase but also on the template position and type of error (for a review, see reference 28a).…”

Section: Discussionmentioning

confidence: 99%

Fidelity of two retroviral reverse transcriptases during DNA-dependent DNA synthesis in vitro.

Roberts¹,

Preston²,

Johnston³

et al. 1989

Mol. Cell. Biol.

182

123

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We determined the fidelity of avian myeloblastosis virus and Moloney murine leukemia virus reverse transcriptases (RTs) during DNA synthesis in vitro using the M13mp2 lacZa gene as a mutational target Retroviral reverse transcriptases (RTs) (EC 2.7.7.7) are DNA polymerases that transcribe retroviral genomic RNA into double-stranded DNA. RT was first identified in virions of murine leukemia virus (MuLV) by Baltimore (1) and Rous sarcoma virus by Temin and Mizutani (54). These enzymes perform multiple enzymatic functions, including the copying of RNA into DNA, the hydrolysis of the RNA from an RNA-DNA hybrid (RNase H), and the copying of singlestranded DNA into double-stranded DNA; thus, RT plays a central role in the life cycle of retroviruses (55,56).The physical structure of purified RT from avian and murine retroviruses has been studied extensively (for a review, see reference 58). Avian retrovirus RT is a heterodimeric molecule containing two related subunits, one with a molecular size of -63 kilodaltons (the a subunit) and the other -95 kilodaltons (the ( subunit) (18). These two proteins, along with a pp32Pol phosphoprotein endonuclease, are derived by differential processing of a pol polyprotein precursor (45). The endonuclease specifically nicks DNA at the junction of adjacent retroviral long terminal repeat sequences (14). The a subunit of avian RT appears to carry both polymerase and RNase H activities.The murine retroviral RT differs from the avian form in that it is a single 84-kilodalton polypeptide (57). Finestructure mutational analysis of the murine enzyme indicated that both the polymerase and the RNase H activities are contained in this polypeptide, with the polymerase activity mapping to the N terminus and the RNase H activity at the C terminus (52). Thus, the murine RT appears to be analogous to the a subunit of the avian RT.

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Section: Discussionmentioning

confidence: 99%

Fidelity of two retroviral reverse transcriptases during DNA-dependent DNA synthesis in vitro.

Roberts¹,

Preston²,

Johnston³

et al. 1989

Mol. Cell. Biol.

182

123

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“…The related viruses, nontransforming recombinant virus (NTRE-7), Rous-associated virus (RAV)-60, and RAV-2, have been previously described (9).…”

Section: Norton Personal Communication)mentioning

confidence: 99%

Rous sarcoma virus contains sequences which permit expression of the gag gene in Escherichia coli.

Mermer¹,

Malamy²,

Coffin³

1983

Mol. Cell. Biol.

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Several aspects of Rous sarcoma virus gene expression, including transcription, translation, and protein processing, can occur within Escherichia coli containing cloned viral DNA. The viral long terminal repeat contains a bacterial promoter, and viral sequences at or near the authentic viral initiation codon permit the initiation of translation. These signals can direct the synthesis in E. coli of the viral gag gene precursor Pr76 or, when fused to a portion of the lacZ gene, a gag-beta-galactosidase fusion protein. Pr76 is processed into gag structural proteins in E. coli in a process which is dependent upon the gag product p15. These observations suggest that E. coli can be used for the introduction and analysis of mutations in sequences relevant to viral gene expression.

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“…Considerable data now document the extensive genetic variability and potential for rapid evolution of RNA viruses (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19). The molecular basis for this variation is extremely high mutation frequencies per average site in RNA virus genomes (ranging between 10-3 and 10-6 and usually of the order of 10' to .…”

mentioning

confidence: 99%

High frequency of single-base transitions and extreme frequency of precise multiple-base reversion mutations in poliovirus.

Torre

Giachetti

Semler

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

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We employed independent clones of a temperature-sensitive mutant of type 1 poliovirus, to quantitate the frequency of specific U -+ C transitions at nucleotide 5310, within the genomic region encoding polypeptide 3AB, which is involved in the initiation ofRNA replication.Only this U --C base substitution restores the wild-type phenotypic ability to form plaques at 39C; the other two base substitutions at this site are lethal. The observed frequency of this specific transition averaged 2 x i0S, and all revertant viruses forming plaques at39°C contained the expected cytidine at nucleotide 5310. Incredibly, only 3 of 10 revertants exhibited this one specific U --C transition whereas 7 of 10 exhibited this same transition plus four additional base substitutions that precisely reverted temperature-sensitive 3AB-310/4 to wildtype poliovirus sequence (these latter four mutations had been introduced into 3AB-310/4 as silent third base mutations to provide new restriction sites in infectious cDNAs). No other mutations were detected in this polypeptide 3AB domain in either the single-base or the precise 5-base revertants. No intermediates were seen; all revertants exhibited either the single U --C transition at nucleotide 5310 or the same transition plus four precise reversions to the wild-type sequence at sites 8, 11, 43, and 46 bases distant from nucleotide 5310. Similar results were obtained after transfection of cDNAderived transcripts. We discuss possible mechaniss for our data. These include (but may not be limited to) error-prone polymerase activity, sequential RNA recombination events joining independent mutations, or some unusual RNA editing process.Considerable data now document the extensive genetic variability and potential for rapid evolution of RNA viruses (1-19). The molecular basis for this variation is extremely high mutation frequencies per average site in RNA virus genomes (ranging between 10-3 and 10-6 and usually of the order of 10' to 10-5). Such high mutation frequencies dictate that even clones of RNA viruses are not homogeneous populations but consist of complex "mutant swarms" or "quasispecies" populations (20)(21)(22)(23)(24)(25)(26). By virtue of their extreme heterogeneity, quasispecies populations can adapt rapidly to new environments by selection of variants preexisting within the population. Some very low polymerase error values have been reported for poliovirus. Thus, Parvin et al. (27) have estimated a poliovirus mutation rate of <10-6 per site for viable neutral or quasineutral mutants of poliovirus.A similar low error frequency of 2.5 x 10-6 was estimated for the reversion of a poliovirus amber mutant (28). In contrast, frequencies of resistance to monoclonal antibody neutralization for poliovirus are in the range 10-3 to 10-5 base substitutions per site (29,30). In vitro measurements of poliovirus polymerase error frequencies (31) and the mutation frequency of poliovirus type 1 to a high degree of resistance to guanidine indicated specific single-site mutation frequencies...

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Variation in Avian Retrovirus Genomes*

Cited by 64 publications

References 38 publications

Fidelity of two retroviral reverse transcriptases during DNA-dependent DNA synthesis in vitro.

Fidelity of two retroviral reverse transcriptases during DNA-dependent DNA synthesis in vitro.

Rous sarcoma virus contains sequences which permit expression of the gag gene in Escherichia coli.

High frequency of single-base transitions and extreme frequency of precise multiple-base reversion mutations in poliovirus.

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