Ribonucleic Acid-Dependent Deoxyribonucleic Acid Polymerase in Visna Virus
TL;DR: A ribonucleic acid-dependent deoxyribonuclidean acid polymerase was found in virions of visna virus as mentioned in this paper, which was resistant to ribonuclease and alkaline hydrolysis, but susceptible to the digestion of deoxy ribinuclease.
Abstract: A ribonucleic acid-dependent deoxyribonucleic acid polymerase was found in virions of visna virus. The enzyme product was resistant to ribonuclease and alkaline hydrolysis but susceptible to the digestion of deoxyribonuclease.
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TL;DR: It is hypothesized that the leukovirus RNA-directed DNA polymerase activity is an integral part of the ribonucleoprotein core of the virions, which suggests that the virion enzyme activity is related to normal cellular DNA polymerases, and that there are homologies between the amino acid sequences of the viral enzyme and normal cellular enzymes.
Abstract: Publisher Summary The discovery of RNA-directed DNA synthesis in disrupted virions of RNA tumor viruses added strong support to the hypothesis that information transfer from RNA to DNA exists in biological system. The chapter discusses the properties of the endogenous reaction carried out by the virion DNA polymerase. To study the endogenous reaction disrupted, virions are incubated with substrates in the absence of any added template and synthesis of DNA is observed using the RNA present in the virions as template. The chapter also discusses the general implications of RNA-directed DNA synthesis in relation to tumor viruses, neoplastic cells, and normal cells. It is hypothesized that the leukovirus RNA-directed DNA polymerase activity is an integral part of the ribonucleoprotein core of the virions. The cores are synthesized in cells as precursor particles and then are incorporated into complete virions when the virions are assembled by budding at the cell surface. This core enzyme system contains not only the template-primer RNA, a DNA polymerase that can transfer information from RNA to double-stranded DNA, but ancillary enzymes, such as polynucleotide ligase and nucleases, which may aid in integrating the viral information with cellular DNA. This suggests that the virion enzyme activity is related to normal cellular DNA polymerases, and that there are homologies between the amino acid sequences of the viral enzyme and normal cellular enzymes. The relationship of RNA-directed DNA synthesis to neoplasia depends upon the relationship of RNA tumor viruses to neoplasia, which is supported by three general hypotheses: the provirus model, the oncogene model, and the protovirus model.
400 citations
TL;DR: It is shown that macrophages became persistently infected when inoculated in culture and were an invariable source of virus from experimentally and naturally infected animals, with inferences to the well-known phenomenon of restricted virus replication in infected animals and the immunopathological aspects of the diseases.
Abstract: Lentiviruses of sheep and goats cause slowly progressive diseases of the central nervous system (visna), lungs (maedi) and joints (arthritis) in their natural hosts. However, the virus target cell(s) in these diseases are still unknown. In this report, using laboratory-adapted Icelandic visna virus and several field strains recently obtained from sheep and goats with natural disease in the U.S.A., we show that macrophages became persistently infected when inoculated in culture. Furthermore, macrophages were an invariable source of virus from experimentally and naturally infected animals. Virus-producing macrophages developed minimal cytopathic changes and virus assembly occurred mainly intracellularly, accumulating in cytoplasmic vacuoles. In contrast to macrophages, sheep choroid plexus fibroblasts developed syncytial cytopathic changes after inoculation and virus maturation occurred at the cell surfaces. Replication of the Icelandic virus was highly productive in this system but that of the field viruses was very inefficient. In some cases these agents failed to replicate in the fibroblasts and no cytopathic effect occurred. This block in the field virus replication was, however, overcome when infected nonproducer fibroblasts were co-cultivated with macrophages. In these cases, virus production with attendant cytopathic effect in the fibroblasts required the continuous presence of macrophages because the cells reverted to a non-productive state when separated from macrophages and became productive again when subcultures were added to new macrophages. The roles of the macrophage as a virus target cell and virus inducer in the virus-macrophage-fibroblast interactions are discussed with inferences to the well-known phenomenon of restricted virus replication in infected animals and the immunopathological aspects of the diseases.
272 citations
TL;DR: The reverse transcriptase activity that, until now, has been presumed to mediate Ty transposition and show that it is sequestered in virus-like particles that also contain Ty RNA is identified.
Abstract: The Ty element of yeast represents a class of eukaryotic transposons that show remarkable structural similarity to retroviral proviruses1,2. Recently, these comparisons have been strengthened by a series of observations on the yeast Ty element: (1) Ty transposes via an RNA intermediate3; (2) it contains a sequence (Fig. 1) which, when translated, is homologous to a conserved region found in all reverse transcriptases4,5; (3) a fusion protein encoded by Ty is produced by a frameshift event that is directly analogous to the production of Pr180gag–polin a retrovirus such as Rous sarcoma virus5,6. Here we identify the reverse transcriptase activity that, until now, has been presumed to mediate Ty transposition and show that it is sequestered in virus-like particles that also contain Ty RNA.
159 citations
TL;DR: The hypothesis is advanced here that the persistence of visna virus is the consequence of its ability, held in common with RNA tumor viruses, to transfer its genetic information to a DNA replica, or provirus, that resides in the cell and allows the virus to elude the host defensive response.
Abstract: In 1954, the late Bjorn Sigurdsson drew attention to an unusual class of slow infection distinguished by a prolonged incubation period and a protracted symptomatic phase. Sigurdsson’s concept of slow infection resulted from his observations on the natural history of a group of diseases of Icelandic sheep. In this review, the focus is on one of these diseases, visna, as a prototype of slow infections caused by viruses, and as a paradigm of the challenging questions raised by slow infections: the persistence of virus in the face of the host’s defensive response, the strikingly slow pace of replication of virus, and the basis of the tissue lesions. Because visna virus is closely related to RNA tumor viruses, these central issues are discussed against the background of the structure and replication of RNA tumor viruses. In particular, the hypothesis is advanced here that the persistence of visna virus is the consequence of its ability, held in common with RNA tumor viruses, to transfer its genetic information to a DNA replica, or provirus, that resides in the cell and allows the virus to elude the host defensive response.
141 citations
TL;DR: A DNA polymerase that can copy RNA–RNA and RNA–DNA synthetic templates has been found in normal mouse and normal human cells and has properties similar to those of the mouse leukaemia virus enzyme.
Abstract: A DNA polymerase that can copy RNA–RNA and RNA–DNA synthetic templates has been found in normal mouse and normal human cells Partially purified polymerases from both sources have properties that are similar to those of the mouse leukaemia virus enzyme
109 citations
References
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Journal Article•
TL;DR: Procedures are described for measuring protein in solution or after precipitation with acids or other agents, and for the determination of as little as 0.2 gamma of protein.
289,852 citations
TL;DR: Two independent groups of investigators have found evidence of an enzyme in virions of RNA tumour viruses which synthesizes DNA from an RNA template, apparently the classical process of information transfer from DNA to RNA can be inverted.
Abstract: Two independent groups of investigators have found evidence of an enzyme in virions of RNA tumour viruses which synthesizes DNA from an RNA template. This discovery, if upheld, will have important implications not only for carcinogenesis by RNA viruses but also for the general understanding of genetic transcription: apparently the classical process of information transfer from DNA to RNA can be inverted.
1,872 citations
TL;DR: Viral RNA-dependent DNA Polymerase: RNA- dependent DNA polymerase in Virions of Rous Sarcoma Virus and its role in cell reprograming is studied.
Abstract: Viral RNA-dependent DNA Polymerase: RNA-dependent DNA Polymerase in Virions of Rous Sarcoma Virus
1,833 citations
590 citations
TL;DR: The virus of Visna, a slow, demyelinating leucoencephalitis of sheep, has been cultivated in tissue culture and neutralizing antibody has been detected in sera from a certain proportion of sheep affected with Visna.
Abstract: The virus of Visna, a slow, demyelinating leucoencephalitis of sheep, has been cultivated in tissue culture. The cells employed are derived from the chorioid plexus of sheep. The virus causes characteristic cytopathic changes in the culture, so that the method may be used to detect virus activity and measure the activity of virus containing material. Virus which had undergone 3, 11, and 12 passages in TC was injected intracerebrally into sheep and found to produce typical Visna lesions. Neutralizing antibody has been detected in sera from a certain proportion of sheep affected with Visna. The rate of virus multiplication in tissue culture after inocula of varying size has been studied. Small inocula tend to give rise to a mild infection which persists in the culture for long periods of time without destroying more than a certain proportion of the cells. The possible relationship between this relatively stable balance between virus and cells and the extraordinarily slow progress of Visna in the CNS of sheep is discussed.
158 citations