Mouse leukemia virus activation by chemical carcinogens

The induction of lymphomas in C57BL mice by methylcholanthrene, urethan, or diethylnitrosamine was accompanied by the development of murine leukemia viral antigen in most of the lymphoid tumors. The cell-free transmission of lymphomas induced by methylcholanthrene and the development of antibody to murine leukemia virus prior to the detection of overt lymphoma in these mice suggest that unmasking of a latent leukemia virus is an indigenous actuating cause of the lymphomas.     

Vaccinia dermal infection and methylcholanthrene in cortisone-treated mice

Cortisone-treated mice were inoculated with vaccinia virus, and then five paintings of methylcholanthrene were applied over the site of inoculation. In 70 percent of the mice, tumors developed at the site of inoculation, and 35 percent of the mice, with and without skin tumors, also developed lymphomas. Identically treated control mice that were vacciniaimmune developed a significantly lower incidence (38 percent) of both skin tumors and lymphomas     

Infection of normal human epithelial cells by Epstein-Barr virus

Primary cultures of epithelial cells were grown from the tonsils and adenoids of patients with diseases not related to Epstein-Barr virus. The cells could not be infected by Epstein-Barr virus. Fluorescein-labeled Epstein-Barr virus and a cytofluorograph were then used to show that the epithelial cells do not have detectable receptors for the virus. However, implantation with Epstein-Barr virus receptors gave the cells the ability to bind the labeled virus. One to 5 percent of receptor-implanted cells exposed to the transforming B95-8 substrain of the virus expressed Epstein-Barr nuclear antigen. The early and viral capsid Epstein-Barr virus-determined antigens were not detected in the virus-infected cultures. The results show that normal human epithelial cells from the nasopharynx become susceptible to infection by Epstein-Barr virus when the membrane barrier resulting from the lack of viral receptors is overcome by receptor implantation.     

Multiple Ebola virus transmission events and rapid decline of central African wildlife

Several human and animal Ebola outbreaks have occurred over the past 4 years in Gabon and the Republic of Congo. The human outbreaks consisted of multiple simultaneous epidemics caused by different viral strains, and each epidemic resulted from the handling of a distinct gorilla, chimpanzee, or duiker carcass. These animal populations declined markedly during human Ebola outbreaks, apparently as a result of Ebola infection. Recovered carcasses were infected by a variety of Ebola strains, suggesting that Ebola outbreaks in great apes result from multiple virus introductions from the natural host. Surveillance of animal mortality may help to predict and prevent human Ebola outbreaks.     

Epstein-Barr virus: detection of genome in somatic cell hybrids of Burkitt lymphoblastoid cells

Somatic cell hybrids of Burkitt lymphoblastoid cells, from which Epstein-Barr virus can be recovered, were examined for the presence of virus DNA by DNA-RNA hybridization. Four clones of hybrid cells, each negative for virus antigens by immunofluorescence, contained virus DNA in varying genomic equivalents. The number of virus genome equivalents increased in the hybrid cells after induction of virus with iododeoxyuridine.     

Lymphomas in mice: failure of induction after a graft-versus-host reaction

A mild graft-versus-host reaction induced in (BALB/cJ x DBA/2J) F(1) mice by the administration of parental spleen cells that differ at several weak histocompatibility loci did not influence the development of lymphomas in these animals. Rous sarcoma virus also failed to induce tumors in the runt and control animals. Breast carcinomas, presumably due to contamination of the inoculums with mammary tumor virus, occurred in those experimental groups given parental cells, whether or not they were viable or immunologically competent. We found no evidence that the immunologic process-as represented by the graft-versus-host reaction-is causally related to the induction of neoplasia.     

Genomic analysis of the human B-lymphotropic virus (HBLV)

The human B-lymphotropic virus (HBLV) has a double-stranded DNA genome of greater than 110 kilobase pairs, which is consistent with its morphological classification as a herpesvirus. A 9000-base pair cloned probe of HBLV detected specific sequences in DNA and RNA of infected cells but did not hybridize to the genomic DNA of other human herpesviruses including the Epstein-Barr virus, human cytomegalovirus, herpes simplex type I, and varicella-zoster virus. Conversely, while probes obtained from each of the known human herpesvirus readily detected the homologous viral DNA, they did not hybridize to genomic HBLV DNA. This evidence, in addition to serological and morphological distinctions and the biological effects of this virus demonstrate that HBLV is a novel human herpesvirus.     

Differential reactivity of human serums with early antigens induced by Epstein-Barr virus

Inoculation of 64-10 or Raji cultures with Epstein-Barr virus derived from the HRI-K clone of the P3J Burkitt's lymphoma line caused abortive infections in most of the lymphoblastoid cells with synthesis of "early antigens" but few, if any, capsids. Antibodies to early antigens were detected by indirect immunofluorescence in serums of many patients with infectious mononucleosis, Burkitt's lymphoma, or nasopharyngeal carcinoma. These antibodies were rarely present in other serums even though some of them showed high titers of antibodies to Epstein-Barr virus when assayed on EB3 Burkitt tumor cells; they also prevented synthesis of early antigens, provided the serums were mixed with the virus prior to inoculation. Antibodies to early antigens possibly reflect current or recent disease processes that are associated with the virus.     

Adaptation of lymphadenopathy associated virus (LAV) to replication in EBV-transformed B lymphoblastoid cell lines

A strain of lymphadenopathy associated retrovirus ( LAV ) passaged in vitro was used to infect a lymphoblastoid cell line obtained by transformation with Epstein-Barr virus of B lymphocytes from a healthy donor. The virus produced from this line (B- LAV ) was also able to grow at a high rate in some other lymphoblastoid lines and in a Burkitt lymphoma line. This adapted strain retained the biochemical, ultrastructural, and antigenic characteristics of the original strain, as well as its tropism for normal T4+ lymphocytes. It is thus possible to grow LAV in large quantities that can be used for the preparation of diagnostic reagents. The interaction between such a human retrovirus and Epstein-Barr virus, a DNA virus, may have some implication for the pathology of the acquired immunodeficiency syndrome and related diseases.     

Deficient natural killer cell activity in x-linked lymphoproliferative syndrome

The activity of natural killer cells was found to be deficient in 10 of 12 males with X-linked lymphoproliferative syndrome, a life-threatening proliferation of lymphocytes after infection by Epstein-Barr virus. The activity levels of natural killer cells from affected males were increased after treatment with interferon in vitro, but normal levels of killing were not obtained. Deficient activity of killer cells in individuals with immunodeficiency and chronic infection by Epstein-Barr virus may contribute to the development of lymphoproliferative disorders.     

Avian v-myc replaces chromosomal translocation in murine plasmacytomagenesis

Deregulation of c-myc expression in association with chromosomal translocations occurs in over 95% of murine plasmacytomas, rat immunocytomas, and human Burkitt lymphomas. Infection with a murine retrovirus (J-3) containing an avian v-myc rapidly induced plasmacytomas in pristane-primed BALB/cAn mice. Only 17% of the induced plasmacytomas that were karyotyped showed the characteristic chromosomal translocations involving the c-myc locus. Instead, all of the translocation-negative tumors demonstrated characteristic J-3 virus integration sites that were actively transcribed. Thus, the high levels of v-myc expression have replaced the requirement for chromosomal translocation in plasmacytomagenesis and accelerated the process of transformation.     

HTLV-V: a new human retrovirus isolated in a Tac-negative T cell lymphoma/leukemia

A new human retrovirus was isolated from a continuous cell line derived from a patient with CD4+ Tac- cutaneous T cell lymphoma/leukemia. This virus is related to but distinct from human T cell leukemia/lymphoma virus types I and II (HTLV-I and HTLV-II) and human immunodeficiency virus (HIV-1). With the use of a fragment of provirus cloned from one patient with T cell leukemia, closely related sequences were found in DNA of the cell line and of tumor cells from seven other patients with the same disease; these sequences were only distantly related to HTLV-I. The phenotype of the cells and the clinical course of the disease were clearly distinguishable from leukemia associated with HTLV-I. All patients and the wife of one patient showed a weak serological cross-reactivity with both HTLV-I and HIV-1 antigens. None of the patients proved to be at any apparent risk for HIV-1 infection. The name proposed for this virus is HTLV-V, and the date indicate that it may be a primary etiological factor in the major group of cutaneous T cell lymphomas/leukemias, including the sporadic lymphomas known as mycoses fungoides.     

Herpes simplex virus glycoprotein D: human monoclonal antibody produced by bone marrow cell line

Normal bone marrow cells from a donor positive for herpes simplex virus were transformed with Epstein-Barr virus. The resulting lymphoblastoid cell line has secreted immunoglobulin G1 of the kappa type continuously for 2 years. This immunoglobulin, detected both on the cell surface and in the cytoplasm, reacts with cells infected with herpes simplex virus. It defines an antigen that comigrates with the 55-kilodalton glycoprotein D of herpes simplex virus type 1 and neutralizes the infectivity of herpes simplex viruses 1 and 2.     

Language discrimination by human newborns and by cotton-top tamarin monkeys

Humans, but no other animal, make meaningful use of spoken language. What is unclear, however, is whether this capacity depends on a unique constellation of perceptual and neurobiological mechanisms or whether a subset of such mechanisms is shared with other organisms. To explore this problem, parallel experiments were conducted on human newborns and cotton-top tamarin monkeys to assess their ability to discriminate unfamiliar languages. A habituation-dishabituation procedure was used to show that human newborns and tamarins can discriminate sentences from Dutch and Japanese but not if the sentences are played backward. Moreover, the cues for discrimination are not present in backward speech. This suggests that the human newborns' tuning to certain properties of speech relies on general processes of the primate auditory system.     

Oncogenicity of the simian adenoviruses

Five of 17 adenoviruses of rhesus or cynomolgus monkey origin induced tumors in newborn hamsters. The tumors appeared between 42 and 280 days after subcutaneous inoculation and had the general characteristics of lymphomas. The tumors were specific by cross-complement fixation tests. An adenovirus recovered from Cercopithecus monkeys appeared to be highly oncogenic; all 23 inoculated hamsters developed tumors within 30 to 40 days.     

p53 mutations in human cancers

Mutations in the evolutionarily conserved codons of the p53 tumor suppressor gene are common in diverse types of human cancer. The p53 mutational spectrum differs among cancers of the colon, lung, esophagus, breast, liver, brain, reticuloendothelial tissues, and hemopoietic tissues. Analysis of these mutations can provide clues to the etiology of these diverse tumors and to the function of specific regions of p53. Transitions predominate in colon, brain, and lymphoid malignancies, whereas G:C to T:A transversions are the most frequent substitutions observed in cancers of the lung and liver. Mutations at A:T base pairs are seen more frequently in esophageal carcinomas than in other solid tumors. Most transitions in colorectal carcinomas, brain tumors, leukemias, and lymphomas are at CpG dinucleotide mutational hot spots. G to T transversions in lung, breast, and esophageal carcinomas are dispersed among numerous codons. In liver tumors in persons from geographic areas in which both aflatoxin B1 and hepatitis B virus are cancer risk factors, most mutations are at one nucleotide pair of codon 249. These differences may reflect the etiological contributions of both exogenous and endogenous factors to human carcinogenesis.     

Murine leukemia: a virus-induced autoimmune disease?

Thymocytes from mice carrying Moloney murine leukemia virus since birth are cytotoxic for normal syngeneic fibroblasts; they are much less cytotoxic for the same cells infected with this virus. The cytotoxic thymocytes appear to increase in number with age of the carrier mice and are present both during preleukemic and leukemic periods. These results suggest that lymphomas in carrier mice result from a sequence of events initiated by intrathymic destruction of normal cells by virus-infected cells, and culminating in the unrestricted proliferation of autoaggressive clones in the thymic cortex.     

Natural antibodies to human retrovirus HTLV in a cluster of Japanese patients with adult T cell leukemia

Human T cell lymphoma leukemia virus (HTLV) is a human retrovirus (RNA tumor virus) that was originally isolated from a few patients with leukemias or lymphomas involving mature T lymphocytes. Here we report that the serum of Japanese patients with adult T cell leukemia, but not the serum of tested normal donors, contains high titers of antibodies to HTLV. These observations, together with data from Japan showing that adult T cell leukemia is endemic in southwest Japan, suggest that HTLV is involved in a subtype of human T cell malignancy, including Japanese adult T cell leukemia.     

Morphological transformation in vitro of human fibroblasts by Epstein-Barr virus: preliminary observations

Human embryo fibroblasts have undergone morphological transformation in vitro after infection by Epstein-Barr virus. The fibroblasts were maintained in suspension during exposure to the virus, and further treatment with inactivated Sendai virus increased the transformation rate. The transformed cells were large and polygonal and grew in discrete, heaped up, foci.     

Gamma interferon synthesis by human thymocytes and T lymphocytes inhibited by cyclosporin A

Cyclosporin A depresses the synthesis of gamma interferon by human thymocytes and T lymphocytes in vitro. This observation is of potential clinical significance because the long-term treatment of transplant patients with cyclosporin A, a widely used immunosuppressive agent, can give rise to B-cell lymphoma resulting from Epstein-Barr virus activation.