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Biomedical subjects

D Baltimore

Publications and source records attributed to D Baltimore.

At least 433 records · Page 24Linked to original sources
PubMed1976

Effect of Fv-1 gene product on synthesis of N-tropic and B-tropic murine leukemia viral RNA.

The production of virus and the synthesis of virus-specific RNA has been studied in Fv-1n/n (NIH/3T3, SIM) and Fv-1b/b (BALB/3T3, SIM-R) cell lines after infection with N- or B-tropic MuLV. It was found that virus production, measured by reverse transcriptase activity in the medium, was 70-100 fold lower in cells resistant at the Fv-1 locus than in permissive cells. The virus-specific RNA, detected by hybridization. In RNA excess with complementary DNA, was reduced by approximately 70-100 fold in cytoplasm of resistant cells compared to permissive cells. A reduction of the same magnitude was observed in the levels of virus-specific RNA extracted from nuclei of resistant cells. Our data therefore show that virus-specific RNA levels are reduced in cells nonpermissive at the Fv-1 locus, suggesting that restriction of the Fv-1 gene product occurs at the level of transcription of the viral genome or at a pre-integration step, or, alternatively, that the RNA transcripts are rapidly degraded after their synthesis.

Cell Line↗
PubMed1976

5'-terminal structure of poliovirus polyribosomal RNA is pUp.

Poliovirus RNA purified from virus-specific polyribosomes does not contain m7G in a 5'-5'-pyrophosphate linkage at its 5'-end. The only potential 5'-end found in ribonuclease digests of this RNA is pUp, which is present in a yield of 1 mole/mole of poliovirus RNA. We conclude that a 5'-terminal m7G is not required for translation of at least one RNA species in animal cells.

Base Sequence↗
PubMed1976

Effect of Fv-1 gene product on proviral DNA formation and integration in cells infected with murine leukemia viruses.

The amounts of unintegrated murine leukemia virus-specific DNA detected by molecular hybridization in extracts of Fv-ln/n (strains NIH/3T3, SIM) or Fv-lb/b (strains JLS-V9, SIM.R) mouse cells after infection with N- or B-tropic viruses were found to be the same in both permissive and resistant cells. Therefore, formation of DNA products from the viral RNA template does not appear to be grossly affected by the Fv-l gene product. Integration of virus-specific DNA into chromosomal cellular DNA was assayed by hybridization of radioactive complementary DNA to DNA from infected cells. With either NIH/3T3 or SIM.R cells infected with N- or B-tropic viruses, integration of proviral DNA could be detected in permissive cells but not in nonpermissive cells. The Fv-l gene product therefore appears to prevent integration of proviral DNA.

Animals↗
PubMed1976

Translation of murine leukemia virus RNA in cell-free systems from animal cells.

The virion RNA of Moloney murine leukemia virus (MuLV) has been translated in eukaryotic cell-free systems derived from mouse L- and human HeLa cells. In both systems at least three polypeptides, approximately 60,000, 70,000, and 180,000 in apparent molecular weight, were formed in response to the added 35S MuLV RNA. All three polypeptides were precipitable with antiserum to detergent-disrupted MuLV. Fingerprint analysis of tryptic digests indicated that all three contain anino acid sequences in common with each other and with the major methionine-containing structural proteins of the virion.

Amino Acid Sequence↗
PubMed1976

Size of murine RNA tumor virus-specific nuclear RNA molecules.

About 1% of the total RNA of cell lines producing murine leukemia virus is virus-specific RNA. About one-third of the virus-specific RNA is located within the nucleus. The size distribution of virus-specific RNA was determined before and after denaturation. Before denaturation, virus-specific RNA sequences sedimented as a heterogeneous population of RNA molecules, some of which sedimented very rapidly. After denaturation, most of the virus-specific RNA had a sedimentation coefficient of 35S or lower, but a small fraction of the nuclear virus-specific RNA sedimented more rapidly than 35S RNA even after denaturation.

Cell Line↗
PubMed1975

Terminal deoxynucleotidyl transferase activity in human leukemic cells and in normal human thymocytes.

Peripheral leukocytes from patients with and without leukemia were assayed for presence of terminal deoxynucleotidyl transferase. Activity of this enzyme was detected in circulating leukemic cells from 11 to 13 patients with acute lymphoblastic leukemia, and in one of four with chronic myelogenous leukemia in blast crisis, but not in leukocytes from patients with other kinds of leukemia or in normal leukocytes. Its presence in a patient with chronic myelogenous leukemia in blast crisis lends biochemical support to the suggestion that some patients with chronic myelogenous leukemia undergo a lymphoblastic rather than a myeloblastic crisis. The thymocyte and leukemic-cell enzyme have the same substrate and primer preference. Normal thymocytes and leukemic cells contain two forms of terminal deoxynucleotidyl transferase that can be separated by phosphocellulose chromatography. The enzyme may provide a means for classifying leukemic cells on a biochemical basis independently of classic morphologic and clinical criteria.

Adolescent↗
PubMed1975

Murine terminal deoxynucleotidyl transferase: cellular distribution and response to cortisone.

The mouse thymus contains two forms of terminal deoxynucleotidyl transferase (TdT) which are distinguishable by the salt concentration necessary to elute them from a phosphocellulose column, by their distrubtion among the thymocyte subpopulations, and by their sensitivity to cortisone treatment. In the whole thymus the later eluting peak (peak II) is the predominant one with about 3-10% of the total activity appearing in peak I. Both peak I and peak II activities are most sensitively assayed by the polymerization of dGMP onto an oligo(dA) primer. The minor population of thymocytes which is less dense and cortisone-resistant contains a higher specific activity of peak I TdT. The majority of TdT activity is, however, found in the major population of thymocytes which occurs in the center region of a bovine serum albumin gradient and is cortisone-sensitive. A very low level of an activity indistinguishable from peak II TdT activity is also detected in the mouse bone marrow. Other tissues, such as spleen, liver, heart, and brain lack detectable amounts of TdT activity.

Animals↗
PubMed1975

Studies on the function of polyadenylic acid on poliovirus RNA.

RNAase H was used to remove selectively over 83% of 3' terminal polyadenylic acid [poly(A)] from poliovirus RNA. In a single cycle infection with this poly(A)-deficient RNA, no evidence for multiplication of the RNA was found. To elucidate further the function of poliovirus poly (A), the translational capacity of the RNAase H-treated and untreated RNA was studied in a cell-free protein synthesizing system prepared from HeLa cells. Removal of most of the poly(A) did not affect the pattern or amount of polypeptides synthesized. We conclude that the poly(A) on poliovirus RNA is probably necessary to the replication of the molecule.

Cell-Free System↗
PubMed1975

Complete translation of poliovirus RNA in a eukaryotic cell-free system.

Poliovirus RNA stimulates imcorporation of 35S from both [35S]methionine and formyl-[35S]methionyl-tRNAfMet in cell-free systems derived from HeLa cells or from poliovirus-infected HeLa cells. The largest product formed under the direction of the viral RNA is the same size as the polyprotein thought to represent translation of the entire RNA. Synthesis of this polyprotein and other large products was stimulated greatly by increasing the salt concentration during the reaction from the optimum for initiation (90 mM) to the optimum for elongation (155 mM). Only one initiation peptide could be identified, and a tryptic digest of the product contained mainly peptides that cochromatographed with peptides from authentic viral proteins. The RNA from a deletion mutant of poliovirus initiated protein synthesis at the same site used by standard RNA and programmed synthesis of an appropriately deleted set of polypeptides. The results strongly support the model of translation of poliovirus RNA from a single initiation site into a continuous polyprotein that is cleaved to form the functional proteins. It is suggested that uninfected HeLa cell extracts can carry out the cleavages of nascent polyprotein.

Cell-Free System↗
PubMed1975

In vitro transformation of lymphoid cells by Abelson murine leukemia virus.

Cell cultures prepared from fetal murine liver were infected by Abelson murine leukemia virus. After about 2 weeks, proliferating cells of lymphoid morphology appeared in some of the cultures. Addition of 2-mercaptoethanol to the initial culture medium greatly enhanced the appearance of the lymphoid cells. Immunoglobulin determinants were evident on the cells in some cultures. Continuous passage of the cells in certain cultures was possible and the passaged cells could form tumors after animal inoculation. Because Abelson murine leukemia virus is able to induce in vitro malignant transformation of lymphoid cells, it probably causes leukemia by directly affecting cellular growth control.

Animals↗