Characterization of the continuous, differentiating myeloid cell line (HL-60) from a patient with acute promyelocytic leukemia

Membrane glycoproteins specified by enveloped viruses are important determinants of viral pathogenecity. They are exposed on the surfaces of virions and on the surfaces of infected cells. They mediate entry of the virus into cells and cell-to-cell spread of infection and also influence tissue tropism and host range. As a consequence of the foregoing, viral membrane glycoproteins are also probably the most important elicitors of protective immune responses.

Glycoproteins Specified by Herpes Simplex Viruses

1. The search for cycles 2. Statistical background 3. Instrumental records 4. Proxy data 5. The global climate 6. Extraterrestrial influences 7. Autovariance and other explanations 8. Nothing more than chaos? Appendix Mathematical background.

Weather Cycles: Real or Imaginary?

Previously, type C RNA tumor virus-related components have been described in blood leukocytes from patients with acute myelogenous leukemia. These components, for example, reverse transcriptase, have been shown to be most closely related to those from two oncogenic subhuman primate type C viruses (woolly monkey sarcoma virus and gibbon ape leukemia virus). Now, we report the continuous production of budding type C viruses with the same characteristic reverse transcriptase by three separate culturings of leukocytes from a single bleeding from a patient with acute myelogenous leukemia. These isolations were made possible by the discovery of a source of conditioned media which sustains exponential growth of human myelogenous leukemia cells in liquid suspension culture.

https://science.sciencemag.org/content/sci/187/4174/350.full.pdf

Type C RNA tumor virus isolated from cultured human acute myelogenous leukemia cells.

Climate Change: a Multidisciplinary Approach provides an up-to-date, concise and comprehensive presentation of our current knowledge of climate change and its implications for society. The book begins by giving a balanced coverage of the physical principles of the global climate, its behaviour on all timescales, and the evidence for and consequences of past change. It then reviews how we measure climate change and the statistical methods for analysing data, before exploring its causes and how we can model this behaviour. The final sections discuss predictions of future climate change and the economic and political debate surrounding its prevention and mitigation. This is a valuable undergraduate textbook for a wide range of courses, including meteorology, oceanography, environmental science, earth science, geography, history, agriculture and social science. It will also appeal to a wider general audience of readers in search of a better understanding of climate change.

Climate Change: A Multidisciplinary Approach

STUDIES on human leukaemic cells reveal the presence in the cytoplasmic fraction of an RNase sensitive DNA polymerase1 complexed with 70S RNA2 and virus specific polysomal RNA3. The DNA product of this enzymatic reaction specifically hybridized to leukaemic nuclear DNA and not to nuclear DNA from normal leukocytes4. This does not establish a viral aetiology for human leukaemia, but suggests that such a possibility may exist. The isolation and characterization of virus-like particles may therefore be possible in conditions which induce the leukaemic cells to produce virions. Our approach was based on the observation5 that arginine deprivation of Rous sarcoma virus (RSV) transformed rat cells (which do not synthesize virions) induced the synthesis and release of C type virions. We have found that leukaemic cells, obtained from patients with acute lymphoblastic leukaemia (ALL) and chronic lymphoblastic leukaemia (CLL) and myeloblastic leukaemia, when incubated in an arginine deficient medium, released particles labelled with 3H-uridine which banded at a density of 1.17 g ml−1. These particles were found to contain an RNase sensitive DNA polymerase activity which transcribed DNA from 70S RNA molecules and formed 70S RNA : DNA hybrid molecules.

Particles released from arginine deprived human leukaemic cells.

Type-C RNA tumor virus particles were released from three different human lymphoblastoid cell lines after incubation in arginine-deficient medium. The released virus-like particles were characterized by (a) their ability to band in sucrose gradients at a density of 1.16-1.18 g/ml; (b) the presence of an RNA-directed DNA polymerase activity resembling that of the oncornaviruses; and (c) isolation of cores that band at a density of 1.26-1.27 g/ml in sucrose gradients. Examination of the arginine-deprived human lymphoblastoid cell line strain P3HR-1 by electron microscopy revealed the presence of C-type particles in the intracellular spaces.

Oncornavirus-like particles released from arginine-deprived human lymphoblastoid cell lines.

Incubation of rat cells transformed by Rous sarcoma virus (RSV) in an arginine-deficient medium resulted in accumulation of particles in the culture medium. Such particles did not appear when the transformed rat cells were incubated in a complete medium nor in the medium of primary rat cells which were incubated either in arginine-deficient or complete media. The particles which were released from the arginine-deprived transformed rat cells resemble C-type particles in their properties. These particles band in sucrose gradients at a density of 1.16 g/ml and contain 35S ribonucleic acid (RNA) molecules and a reverse transcriptase activity. Analysis of the cytoplasm of transformed and primary rat cells, deprived and undeprived of arginine, revealed the presence of reverse transcriptase-containing particles which banded in sucrose gradients at a density of 1.14 g/ml. These particles differed from the particles released into the medium by the arginine-deprived RSV-transformed rat cells. The deoxyribonucleic acid (DNA) molecules synthesized in vitro by the reverse transcriptase present in the particles isolated from the medium of arginine-deprived cells hybridized to RSV RNA, whereas the DNA synthesized by the cell-bound enzyme had no homology to RSV RNA.

Reverse transcriptase-containing particles induced in rous sarcoma virus-transformed rat cells by arginine deprivation.

Two cell lines [R(B77) and XC] of Rous sarcoma virus-transformed rat cells were infected with herpes simplex virus type 1 (HSV-1) grown in BSC-1 cells. Analysis of the DNA species synthesized in XC, R

Interaction of herpes simplex virus type 1 with Rous sarcoma virus-transformed rat cells [XC and R(B77) cell lines].

Temin postulated (1,2) that the viral DNA synthesized by the oncorna virion-associated reverse transcriptase (3,4) integrates into the host cell DNA as an essential step in the cellular transformation process. The studies of Hill and Hillova, who demonstrated that permissive cells were transformed by purified DNA molecules from transformed cells (5), confirmed Temin’s hypothesis. Thus, the oncorna virus-transformed cell contains viral DNA sequences in the cellular genome. The mechanism which leads to the integration of the viral DNA molecules into the cellular DNA is not yet known. Also, the cellular mechanisms which control the expression of the viral DNA are not yet understood. In permissive cells, transformation is accompanied by virus production, while in nonpermissive cells transformation occurs but without virus production. These findings suggest that in nonpermissive cells, the transcription of the viral DNA is controlled by the host cell process. Although the viral DNA is repressed in the nonpermissive cells, it was demonstrated (6) that virus synthesis could be induced by fusion of transformed cells with permissive cells. Treatment with 5-bromodeoxyuridine (BUdR) also induced virus replication (7), similar to the effect of arginine deprivation on nonpermissive cells (8). Although the mechanism of virus induction is not understood, the induction of virus replication was used to study the presence of oncorna viruses in cancer cells.

Eynat Weinberg

Papers

Particles released from arginine deprived human leukaemic cells.

Oncornavirus-like particles released from arginine-deprived human lymphoblastoid cell lines.

Reverse transcriptase-containing particles induced in rous sarcoma virus-transformed rat cells by arginine deprivation.

Interaction of herpes simplex virus type 1 with Rous sarcoma virus-transformed rat cells [XC and R(B77) cell lines].

Induction of C-Type Particles in Mammalian Cancer Cells