Relationships between Components in Primate RNA Tumor Viruses and in the Cytoplasm of Human Leukemic Cells: Implications to Leukemogenesis

Gallo, Robert C.; Gallagher, Robert E.; Miller, N. R.; Mondal, H.; Saxinger, W. C.; Mayer, Robert J.; Smith, RG; Gillespie, David

doi:10.1101/sqb.1974.039.01.109

Cited by 63 publications

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“…The possible origin of these antibodies is discussed. Evidence for the presence of oncornavirus particles (1-13) as well as viral antigens (14)(15)(16)(17)(18)(19)(20), RNA-dependent DNA polymerase (reverse transcriptase) (21)(22)(23)(24)(25), and nucleic acids (22,(26)(27)(28)(29) in normal and malignant human tissues has accumulated steadily over the past few years. Another approach to search for C type virus information in humans is to screen sera from healthy individuals and from patients for antibodies reacting with tumor virus antigens.…”

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Human antibodies reactive with purified envelope antigens of primate type C tumor viruses.

Kurth¹,

Mikschy²

1978

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

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Human sera from healthy individuals have been shown to react with viral antigens in preparations of de-tergent-disrupted C type viruses from monkeys. In this report, it is demonstrated that (populations of) these human antibodies react with highly purified envelope glycoproteins of the simian sarcoma virus-simian sarcoma-associated virus complex and the Friend leukemia virus complex. Several immunological parameters influencing human antibody binding to C type tumor virus antigens have been characterized. These parameters indicate that human antibodies tend to bind to what is probably a subset of the antigenic determinants on the virus envelope antigens and that different human sera recognize the same antigenic determinants on the virus envelope antigens tested. The possible origin of these antibodies is discussed. Evidence for the presence of oncornavirus particles (1-13) as well as viral antigens (14-20), RNA-dependent DNA polymerase (reverse transcriptase) (21-25), and nucleic acids (22,(26)(27)(28)(29) in normal and malignant human tissues has accumulated steadily over the past few years. Another approach to search for C type virus information in humans is to screen sera from healthy individuals and from patients for antibodies reacting with tumor virus antigens. The presence of such antibodies may indicate previous viral infection.In the absence of C type tumor virus strains of undisputable human origin, we made use of the observation that comparative analysis of C type animal viruses generally revealed close immunological and biochemical similarities between virus strains isolated from the same or evolutionary related species. It could, therefore, be assumed that the yet putative human C type viruses may share antigenic determinants and nucleic acid homologies with virus strains of higher primates-i.e., monkeys and apes. For this reason we have used structural proteins of C type viruses from monkeys to survey human sera for the presence of antibodies reacting with C type viral antigens.Our previous investigations revealed the presence of antibodies in the majority of human sera that react with antigens in preparations of C type primate viruses (30-3). These data are in agreement with related findings from some laboratories (34-36), but contradict reports from several others that were unable to demonstrate human antibodies reacting with RNA tumor virus antigens (37-39). The reasons for these discrepancies remain unclear at present, but they may have been caused by using different human sera, different immunological detection techniques, virus antigens prepared by different procedures, and different interpretation of the data (discussed in refs. 30 and 31).To resolve these discrepancies, both improvement of the immunological detection techniques and the use of viral antigens purified to homogeneity (40, 41) seemed imperative.This publication deals with the presence of antibodies inThe publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby...

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confidence: 99%

Human antibodies reactive with purified envelope antigens of primate type C tumor viruses.

Kurth¹,

Mikschy²

1978

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

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“…There was no hybridization to DNA from spleen and kidney of a patient with aortic insufficiency or to the DNA from the "normal" lung ( with tumor cells) of a patient with Burkitt's lymphoma (Table 2). Previous studies with normal leukocytes, including phytohemagglutinin-stimulated blood lymphocytes from many donors, also failed to reveal MuLVR-related sequences in DNA of normal tissues (14 (18,31). These observations led to the conclusion that some humans are infected by a virus very closely related to the baboon virus (18,37).…”

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“…USA 74 (1977) viruses highly related to mem'bers of this virus group (25)(26)(27)(28)(29)(30) and, more recently, suggestive evidence for antibodies to this virus group in human sera (19,39,40). However, proviral sequences related to the simian sarcoma virus/gibbon ape leukemia virus group have not as yet been reported (14). Because MuLVR 70S RNA shares some sequence homology to RNA of simian sarcoma virus/gibbon ape leukemia virus, it was possible that the sequences related to MuLVR found in some human tissues were from a virus of this group.…”

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“…This includes evidence in some patients with leukemia and preleukemia of a polymerase related to reverse transcriptase of these viruses (5,6,8,14,41), a protein antigenically related to the virus p30 structural protein (7,(21)(22)(23), and some cytoplasmic nucleic acid sequences (11)(12)(13)(14). There are also some reports of isolation of replicating leukemic blood or bone marrow cells.…”

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“…Data are accumulating that indicate the presence of type-Ctumor-virus-like components in some human tissues . Cytoplasmic nucleic acids with sequences related to the RNA of Rauscher murine leukemia virus (MuLVR) and other viruses have been described (4,(9)(10)(11)(12)(13)(14)(15)(16)(17). Recently, nucleic acids and proteins related to the two known primate type-C virus groups-the simian sarcoma virus/gibbon ape leukemia virus group and the baboon endogenous virus group-have been reported in fresh human tissues (5-8, 11-14, 16, 18-23) (20)(21)(22)(23) have been contested (24).…”

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Rauscher-leukemia-virus-related sequences in human DNA: presence in some tissues of some patients with hemotopoietic neoplasias and absence in DNA from other tissues.

Aulakh¹,

Gallo²

1977

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

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Nature 262,[190][191][192][193][194][195], because there is no sequence homology between nucleic acids from MuLVR and baboon virus. The absence of these nucleic acid sequences in many tissues of patients with neoplasia and from the few tissues examined from people with nonneoplastic disease suggests that they are not endogenous elements but are acquired after fertilization. Taken together with the previous detection of baboon and woolly monkey type-C viral related components in some human tumors, the results suggest acquisition of at least three types of type-C viral sequences in the human population. Data are accumulating that indicate the presence of type-Ctumor-virus-like components in some human tissues (1-23). Cytoplasmic nucleic acids with sequences related to the RNA of Rauscher murine leukemia virus (MuLVR) and other viruses have been described (4, 9-17). Recently, nucleic acids and proteins related to the two known primate type-C virus groups-the simian sarcoma virus/gibbon ape leukemia virus group and the baboon endogenous virus group-have been reported in fresh human tissues (5-8, 11-14, 16, 18-23) The objective of experiments reported here was to examine DNA from human tissues for sequences related to RNA of MuLVR in more detail and with more carefully prepared cDNA probes. We report: (i) detection of nucleic acid sequences distantly related to MuLVR in DNA from spleens of some patients with acute myelogenous leukemia (AML), Hodgkin's disease, and multiple myeloma; (ii) absence of these sequences in DNA from apparently uninvolved tissues of the same patients with neoplasia and from the normal human tissues tested. Since MuLVR and the baboon endogenous virus are not detectably related (32), the detection of MuLVR-related DNA sequences is not explained by the previously reported presence of proviral sequences of baboon virus in DNA from some leukemia patients. Taken together, the results show at least two independent sets of oncornavirus-related sequences in the DNA from some leukemia patients. While the mode, source, and time of acquisition, and relevance to etiology, must be speculative, interspecies transmission of one or both agents may be involved.MATERIALS AND METHODS Purification of DNA from Human Tissues. The tissues used in these experiments were uncultured specimens obtained at the time of autopsy and kept frozen at -80°until the isolation of DNA. The organ tissues obtained from people with neoplasia were infiltrated with tumor cells. The tissues were lysed in a

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On the presence of reverse transcriptase in myelo- and lymphoproliferative disorders

Muijen

Velde

Ottolander

et al. 1979

Cancer

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Buffy coats from 31 patients with a diagnosis of leukemia and 16 normal donors were tested for the presence of a viral-like reverse transcriptase. Eighty-five percent of fresh leukemic buffy coats were positive. Also tested were spleens from 16 patients with hematological disorders and 5 spleens from patients without history of hematological malignancy. The 5 normal spleens were negative. Also negative were 4 spleens from patients with Hairy cell leukemia. From the remaining 12 spleens 7 were positive. Reverse transcriptase measurements can be used to distinguish leukemic from normal buffy coats.

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Relationships between Components in Primate RNA Tumor Viruses and in the Cytoplasm of Human Leukemic Cells: Implications to Leukemogenesis

Cited by 63 publications

References 0 publications

Human antibodies reactive with purified envelope antigens of primate type C tumor viruses.

Human antibodies reactive with purified envelope antigens of primate type C tumor viruses.

Rauscher-leukemia-virus-related sequences in human DNA: presence in some tissues of some patients with hemotopoietic neoplasias and absence in DNA from other tissues.

On the presence of reverse transcriptase in myelo- and lymphoproliferative disorders

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