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P Duesberg

Publications and source records attributed to P Duesberg.

At least 37 records · Page 2Linked to original sources
PubMed1992

HIV-free AIDS reports.

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Acquired Immunodeficiency Syndrome↗
PubMed1992

Unmutated proto-src coding region is tumorigenic if expressed from the promoter of Rous sarcoma virus: implications for the gene-mutation hypothesis of cancer.

The transforming (onc) genes of oncogenic retroviruses share most or all of their coding sequences with normal cellular genes termed proto-onc genes. The viral genes differ from proto-onc genes in virus-specific promoters and in various point mutations and substitutions of cell-derived coding regions. In view of the structural similarities between viral oncogenes and cellular proto-onc genes, the hypothesis has been advanced that proto-onc genes become cellular cancer genes if they have suffered mutations. Indeed, point mutations and substitutions have been observed in the proto-onc genes of some cancers. However, the hypothesis has been difficult to prove because mutated proto-onc genes from tumors do not transform diploid cells. Moreover, owing to the popularity of this hypothesis, even viral oncogenes are thought to derive transforming function from mutations of this cell-derived coding region. A competing hypothesis proposes that enhanced expression from retroviral promoters is necessary and sufficient for oncogenic function of proto-onc genes. To distinguish between these hypotheses we have tested tumorigenicity of RpSV, a synthetic retrovirus with the normal proto-src coding region in a vector derived from Rous sarcoma virus (RSV). In addition, we have tested the role of RSV-specific src point mutations on the tumorigenicity of RpSV. It was found that RpSV with an unmutated proto-src coding region is tumorigenic in chickens and that tumorigenicity is enhanced by RSV-specific src point mutations. It is concluded that retroviral promoters are essential for the transforming function of viral oncogenes and that certain point mutations merely supplement their transforming function. Thus retroviral onc genes are not models for the hypothesis that mutated, but transcriptionally normal, proto-onc genes of certain tumors are cancer genes.

Animals↗
PubMed1989

Duesberg's PNAS paper.

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Acquired Immunodeficiency Syndrome↗
PubMed1989

Does HIV cause AIDS?

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Acquired Immunodeficiency Syndrome↗
PubMed1986

Conserved chromosomal positions of dual domains of the ets protooncogene in cats, mice, and humans.

The mammalian protooncogene homologue of the avian v-ets sequence from the E26 retrovirus consists of two sequentially distinct domains located on different chromosomes. Using somatic cell hybrid panels, we have mapped the mammalian homologue of the 5' v-ets-domain to chromosome 11 (ETS1) in man, to chromosome 9 (Ets-1) in mouse, and to chromosome D1 (ETS1) in the domestic cat. The mammalian homologue of the 3' v-ets domain was similarly mapped to human chromosome 21 (ETS2), to mouse chromosome 16 (Ets-2), and to feline chromosome C2 (ETS2). Both protooncogenes fell in syntenic groups of homologous linked loci that were conserved among the three species. The occurrence of two distinct functional protooncogenes and their conservation of linkage positions in the three mammalian orders indicate that these two genes have been separate since before the evolutionary divergence of mammals.

Animals↗
PubMed1985

Mutagenesis of avian carcinoma virus MH2: only one of two potential transforming genes (delta gag-myc) transforms fibroblasts.

Avian carcinoma virus MH2 contains two potential transforming genes, delta gag-mht and delta gag-myc. Thus, MH2 may be a model for two-gene carcinogenesis in which transformation depends on two synergistic genes. Most other directly oncogenic viruses contain single, autonomous transforming (onc) genes and are models for single-gene carcinogenesis. To determine which role each potential onc gene of MH2 plays in oncogenesis, we have prepared deletion and frameshift mutants of each of the two MH2 genes by in vitro mutagenesis of cloned proviral DNA and have tested transforming function and virus production in cultured primary quail cells. We have found that mht deletion mutants and wild-type virus transform primary cells and that myc deletion and frameshift mutants do not. The morphologies of cells transformed by the mht deletion mutants and by wild-type MH2 are similar yet vary considerably. Nevertheless, typical mutant transformed cells can often be distinguished from cells transformed by wild-type MH2. We conclude that the delta gag-myc gene transforms primary cells by itself, without the second potential onc gene. This myc-related gene is the smallest that has direct transforming function. delta gag-mht is without detectable transforming function but may affect transformation by delta gag-myc. Thus, MH2 behaves like a virus with a single onc gene, although it expresses two potential onc genes, and it appears not to be a model for two-gene carcinogenesis. Further work is necessary to determine whether the delta gag-mht gene possibly enhances oncogenic function of delta gag-myc or has independent oncogenic function in animals.

Animals↗
PubMed1984

Avian erythroblastosis virus E26: nucleotide sequence of the tripartite onc gene and of the LTR, and analysis of the cellular prototype of the viral ets sequence.

An intact 5.7-kb provirus of the avian erythroblastosis virus E26 has been molecularly cloned for comparisons with avian myeloblastosis virus (AMV) and other avian tumor viruses. E26 and AMV transform hemopoietic cells exclusively. Both cause myeloblastosis, but E26 also causes erythroblastosis. Sequence analysis of the proviral DNA showed that: The tripartite transforming gene of E26 forms a contiguous reading frame of 1046 codons, including 272 gag, 283 mybE, and 491 ets codons. No subgenomic ets-specific mRNA was detected in E26-infected cells. By contrast, the onc gene of AMV consists almost entirely of a mybA sequence expressed via subgenomic mRNA that extends over the 5' and 3' ends of mybE. mybE is only slightly diverged from the mybA homolog of AMV and even less from the cellular proto-myb sequence with no characteristic mutation that sets apart the two viruses from proto-myb. The U5 region of the long terminal repeat (LTR) of E26 and AMV are colinear and differ only in scattered point mutations. The U3 region of the E26 LTR is different from that of AMV but is colinear and closely related with that of avian carcinoma virus MH2 and also with that of Prague Rous sarcoma virus (RSV), except for an unexpected 16-nucleotide substitution of 22 RSV nucleotides. Upstream of the 3' LTR, the c region of E26 appears to be the same as that of RSV for 70 nucleotides and very similar to those of AMV and MH2 for about 20 to 30 nucleotides. Since the U3s of E26, MH2 and RSV are very closely related and neither MH2 nor RSV show a particular erythroblast tropism, it is possible that the U3 does not play a critical role in the erythroblast tropism of E26. Electrophoretic size analyses of chicken DNA digested with restriction enzymes indicate that DNA fragments totaling over 50 kb hybridize with viral ets DNA.

Alpharetrovirus↗
PubMed1982

Structural relationship between a normal chicken DNA locus and the transforming gene of the avian acute leukemia virus MC29.

We screened a recombinant chicken DNA/lambda phage library for sequences homologous to the transformation-specific sequences of the avian acute leukemia virus MC29 by hybridization with molecularly cloned MC29 proviral DNA. Three cellular DNA clones were found and compared with each other and with the viral genome by physical mapping with restriction endonucleases and by heteroduplex analysis. These experiments indicated that the three cellular clones overlap and represent a single cellular locus. The RNA genome of MC29 and normal cell DNA share a homologous region of 1.6 kilobases which is interrupted in the cellular DNA by 1.0 kilobase of sequences not present in the viral genome. Hybridization of the cloned cellular DNA to viral RNA and analysis of the protected viral RNA by fingerprinting techniques indicated that there is extensive sequence homology between the helper virus-unrelated mcv sequences of the viral RNA and the cellular DNA, with only minor base differences. The cellular mcv locus, however, lacks all helper virus-related sequences of MC29, including those of the partial viral gag gene which, together with mcv, encodes the probable transforming protein of MC29. We conclude that although the mcv locus of the normal cell does not represent a complete structural homolog to the onc gene of MC29, it is probably the precursor to the onc-specific sequence in the virus.

Alpharetrovirus↗
PubMed1982

DNA clone of avian Fujinami sarcoma virus with temperature-sensitive transforming function in mammalian cells.

We have molecularly cloned an integrated proviral DNA of Fujinami sarcoma virus (FSV) into a lambda phage vector and further subcloned it into plasmid pBR322. The source of provirus was a quail nonproducer cell clone transformed by FSV. The FSV strain used is temperature sensitive in the maintenance of transformation of avian cells. The recombinant plasmid was shown to contain an entire FSV genome by fingerprinting the hybrids formed with 32P-labeled FSV RNA. This analysis also revealed a previously undetected env-related sequence in FSV which represents the 3' end of the gp85 env gene. A physical map of cloned FSV DNA identifying sites of several restriction enzymes is described. Upon transfection, FSV DNA cloned in pBR322 transformed mouse NIH-3T3 cells, which proved to be temperature sensitive in maintaining transformation. Phosphorylation but not synthesis of p140, the only known gene product of FSV, was also temperature sensitive in these cells. The correlation between transformation and phosphorylation of p140 suggests that phosphorylation of p140 is necessary for transformation of mouse cells, as was shown previously for avian cells. These results provide direct genetic evidence that the mechanisms for maintaining transformation of mammalian and avian cells involve the same FSV gene product, p140. Homology was detected by hybridization between transformation-specific sequences of FSV DNA and certain restriction endonuclease-resistant fragments of cellular DNA of two avian species, chicken and quail. Under the same conditions homology was also detected with DNA of non-avian species, although apparently to a lower degree than with avian cells.

Animals↗
PubMed1979

Anatomy of the RNA and gene products of MC29 and MH2, two defective avian tumor viruses causing acute leukemia and carcinoma: evidence for a new class of transforming genes.

The RNA species of the defective avian acute leukemia virus MC29 and of the defective avian carcinoma virus MH2 and of their helper viruses were analyzed using gel electrophoresis, fingerprinting of RNase T1-resistant oligonucleotides, RNA-cDNA hybridization and in vitro translation. A28S RNA species, of 5700 nucleotides, was identified as MC29- or MH2-specific. MC29 RNA shared 4 out of about 17 and MH2 RNA at least 1 out of 16 T1-oligonucleotides with several other avain tumor virus RNAs. In addition MC29 and MH2 RNAs shared 2 oligonucleotides which were not found in any other viral RNA tested. 60% of each 28S RNA could be hybridized by DNA complementary to other avian tumor virus RNAs (group-specific) but 40% could only be hybridized by homologous cDNA (specific). Src gene-related sequences of Rous sarcoma virus were not found in MC29 or MH2 RNA. The specific and group-specific sequences of MC29, defined in terms of their T1-oligonucleotides, were located on a map of all T1-oligonucleotides of viral RNA. Specific sequences mapped between 0,4 and 0,7 map units from the 3'poly(A) end and group-specific sequences mapped between 0 and 0,4 and 0,7 and 1 map units. The MC29-specific RNA segment was represented by 6 oligonucleotides, two of which were those shared only by MC29 and MH2 RNAs. In vitro translation of MC29 RNA generated a major 120 000 dalton protein and minor 56 000 and 37 000 dalton proteins. The 120 000 dalton protein shared sequences with the proteins of the avian tumor viral gag gene, which maps at the 5' end of independently replicating viruses. Since a gag gene-related oligonucleotide was also found near the 5' end of MC29 RNA, we propose that the 120 000 MC29 protein was translated from the 5' 60% of MC29 RNA. It would then include sequences of the defective gag gene as well as MC29-specific sequences. Since both MC29 and MH2 lack the src (sarcoma) gene of Rous sarcoma virusk it is concluded that they contain a distinct class of transforming (onc) genes. We propose that the specific sequences of MC29 and MH2 represent all, or part of, their onc genes because the onc genes of MC29 and MH2 are specific and represent the only known genetic function of these viruses. If this proposal is correct, the onc genes of MC29 and MH2 would be related, because the specific RNA sequence of MC29 shares 2 of 6 oligonucleotides with MH2. It would also follow that the 120 000 dalton MC29 protein is a probable onc gene product, because it is translated from MC29-specific (and group-specific) sequences and because both MC29- and MH2-transformed cells contain specific 120 000 and 100 000 dalton proteins, respectively.

Avian Leukosis Virus↗