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Biomedical subjects

L O Arthur

Publications and source records attributed to L O Arthur.

At least 91 records · Page 5Linked to original sources
PubMed1986

Prospect for prevention of human immunodeficiency virus infection: purified 120-kDa envelope glycoprotein induces neutralizing antibody.

This study initiates an effort to develop a safe vaccine against the acquired immunodeficiency syndrome (AIDS) that is caused by infection with a retrovirus designated human immunodeficiency virus (HIV) [formerly human T-cell lymphotropic virus type III (HTLV-III)]. Other retrovirus models have shown that purified external glycoprotein subunits are immunogenic. The external envelope glycoprotein of HIV (gp120) has a molecular size of 120 kDa, is responsible for virus infectivity, and induces strong antibody response in humans. Purified HIV virus preparations contain relatively little gp120 so HIV-infected cells were used as the antigen source. The gp120 was localized on cell membranes and was solubilized with low levels of nonionic detergent. The glycoprotein was further purified by immunoaffinity chromatography over a resin prepared from IgGs isolated from patients. Homogeneity was achieved following extensive dialysis and polyacrylamide gel electrophoresis. The gp120 isolated from infected cells was shown to be structurally identical by peptide maps to virion gp120 and the amino-terminal amino acid sequence confirmed that the molecule was specified by the HIV genome. Goat, horse, and rhesus monkey (Macaca mulatta) immune sera to gp120 precipitated the homologous antigen and neutralized the in vitro infectivity of HIV. The induction of neutralizing antibody indicates that a gp120 subunit vaccine against HIV is theoretically possible.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Octapeptides deduced from the neuropeptide receptor-like pattern of antigen T4 in brain potently inhibit human immunodeficiency virus receptor binding and T-cell infectivity.

The differentiation antigen T4, present on the helper/inducer subset of T lymphocytes, is thought to serve as the receptor for the human immunodeficiency virus (HIV). We find that a 60-kDa protein, immunoprecipitable by monoclonal antibody (mAb) OKT4, is present on membranes from human brain as well as human T cells. Furthermore, the radioiodinated HIV envelope glycoprotein [125I-labeled gp120 (125I-gp120)] can be specifically covalently affixed to a molecule present on rat, monkey, and human brain membranes to yield a complex that is indistinguishable from that formed on human T cells. T4 antigen has been studied on unfixed squirrel monkey, rat, and human brain sections by autoradiography using the mAb OKT4. A highly conserved neuroanatomical pattern has been demonstrated, suggesting an analogous organization in these three mammalian brains. Furthermore, the localization of 125I-gp120 receptor binding appears similar to that of T4 and is highly reminiscent of patterns for many previously characterized neuropeptide receptors. A computer-assisted analysis of gp120 suggested that a previously unremarkable octapeptide sequence within the gp120 protein, which we have synthesized and termed "peptide T," may play an important role in HIV attachment. Thus, peptide T and three rationally designed peptide analogs, each with a systematic amino acid substitution, potently inhibit specific 125I-gp120 binding to brain membranes. Additionally, when tested in a viral infectivity assay, these peptides show the same rank order and similar absolute potency to block HIV infection of human T cells. Thus, peptide T may provide a useful pharmacological or immunological basis for the control and treatment of AIDS.

Amino Acid Sequence↗
PubMed1986

Isolation of a lentivirus from a macaque with lymphoma: comparison with HTLV-III/LAV and other lentiviruses.

A retrovirus has been isolated on the human T-cell line HuT 78 after cocultivation of a lymph node from a pig-tailed macaque (Macaca nemestrina) that had died with malignant lymphoma in 1982 at the University of Washington primate center. This isolate, designated MnIV (WPRC-1) (M. nemestrina immunodeficiency virus, Washington Primate Research Center) shows the characteristic morphology of a lentivirus and replicates to high titers in various lymphocyte lines of human and primate origin. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of purified MnIV revealed multiple bands of structural proteins, including a major viral gag protein of 28 kilodaltons, that did not comigrate with the viral proteins of a human immunodeficiency virus (HIV [FRE-1]) that was also isolated on HuT 78 cells. The relatedness of MnIV to other lentiviruses (HTLV-III/LAV, EIAV, and visna) was examined in radioimmunoassays, by immunoblot techniques, and by N-terminal amino acid sequence analysis of the viral p28 gag protein. The immunoassays revealed cross-reactivity only between MnIV p28 and HTLV-III/LAV p24, and sequence analysis showed that 14 of the 24 N-terminal residues of MnIV p28 and HTLV-III/LAV p24 are identical. These results indicate that MnIV belongs to the same lentivirus family as HTLV-III/LAV but is only partially related to these human acquired immune deficiency syndrome retroviruses.

Amino Acid Sequence↗
PubMed1986

Immunodeficiency in rhesus monkeys associated with the original Mason-Pfizer monkey virus.

The Mason-Pfizer monkey virus (MPMV) was reisolated from a cryopreserved sample of the original MPMV-containing rhesus breast carcinoma, and complete integrated MPMV provirus was detected in chromosomal DNA of this tumor. Reanalysis of the in vivo pathogenicity and molecular character of MPMV reisolated from the rhesus breast tumor and analysis of the original MPMV after long-term in vitro propagation in human and rhesus cells show that the original MPMV produces an acquired immunodeficiency similar to that caused by the recently described simian acquired immune deficiency syndrome type D retroviruses, and the MPMV genome and its immunosuppressive effect in vivo have remained stable despite prolonged in vitro passage in human and rhesus cells.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Inapparent carriers of simian acquired immune deficiency syndrome type D retrovirus and disease transmission with saliva.

Simian acquired immune deficiency syndrome (SAIDS) type D retrovirus (SRV) was isolated from saliva, urine, and peripheral blood mononuclear cells of a 6-year-old healthy rhesus monkey (Macaca mulatta) seronegative for antibodies to human T-lymphotropic virus (HTLV) type I, HTLV type III, and simian T-lymphotropic virus type III (STLV-III), identified as an inapparent SAIDS carrier in retrospective epidemiologic studies. This animal was linked to 34 cases of SAIDS over a 3-year period. Two juvenile rhesus monkeys inoculated iv with the SRV-containing saliva from this carrier became persistently infected with the retrovirus and developed SAIDS after 4-6 weeks. Both animals seroconverted to SRV, but neither had detectable preinoculation or postinoculation antibodies against HTLV type I, HTLV type III, or STLV-III. One of these animals died of SAIDS with disseminated cytomegalovirus infection after 24 weeks, and the other remains alive with persistent SRV viremia, generalized lymphadenopathy, and splenomegaly after a transient immunosuppression. Major clinical and pathological features associated with the newly described STLV-III were not observed. SRV was subsequently identified in saliva of 2 additional healthy carriers as well as monkeys with SAIDS. The findings of a carrier state in SAIDS and evidence for saliva transmission of the probable causative virus further support the usefulness of this animal model of nononcogenic immunosuppressive retroviral disease.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Characterization of envelope and core structural gene products of HTLV-III with sera from AIDS patients.

The envelope (env) and structural (gag) gene products of human T-cell leukemia (lymphotropic) virus type III were identified by immunoaffinity chromatography, immunoprecipitation, and two-dimensional oligopeptide mapping methods. The env gene specifies a glycosylated polypeptide with a molecular weight of 160,000 (gp160) that is processed to gp120 and smaller gene products. The gag gene specifies two polypeptides of 70,000 and 55,000 molecular weight (p70 and p55), both of which contain p24, the major structural protein of the mature virion. The techniques in this study can be used to define the extent of variability of the env gene product among different virus isolates and may identify the nature and patterns of the humoral immune response that lead to an immunologically protected state.

Acquired Immunodeficiency Syndrome↗
PubMed1985

The involvement of a type-B retrovirus in the induction of thymic lymphomas.

A highly leukemogenic virus (DMBA-LV) (in vivo leukemogenic titer 1-5 X 10(6) IU/ml, and 35-40 days to thymic lymphoma detection) is produced by a chemical carcinogen-induced transplanted thymic lymphoma. The virus preparation is a mixture of a type-B retrovirus highly related to exogenous type-B retroviral isolates and a biologically defective type-C retrovirus. The DNA of DMBA-LV-induced-tumors contains new type-B proviruses but no additional type-C proviruses could be detected. The leukemogenicity of DMBA-LV was completely neutralized by a monoclonal antibody against MMTV envelope glycoprotein, but was not affected by a broadly reacting Friend MuLV anti-gp70 serum which effectively neutralizes type-C ecotropic, xenotropic, and recombinant retroviruses and which completely abolishes the leukemogenic activity of Moloney leukemia virus. Three type-B mammary tumor-inducing retroviral isolates, while containing type-C retroviral sequences, were not leukemogenic. A further characterization of the type-C retroviral sequences present in DMBA-LV indicated that sequences characteristic of endogenous, nonxenotropic proviruses are present. In addition, using a variety of type-C-specific retroviral DNA probes, no evidence was obtained for the presence of a type-B-C-recombinant genome in DMBA-LV. Leukemogenesis was absolutely dependent upon the presence of a functional type-B retroviral envelope gp 52 and DMBA-LV does not appear to contain a leukemogenic retroviral type-C genome.

Animals↗
PubMed1984

Characterization of exogenous type D retrovirus from a fibroma of a macaque with simian AIDS and fibromatosis.

A novel type D retrovirus was isolated by cocultivation of explants of fibromatous tissue from a rhesus monkey (Macaca mulatta) with immunodeficiency and retroperitoneal fibromatosis. This type D virus, isolated from a macaque with simian acquired immunodeficiency syndrome (SAIDS-D/Washington), is exogenous and is partially related to the Mason-Pfizer and the langur monkey type D viruses. The SAiDS-D virus can be distinguished from all other primate retroviruses by antigenicity and molecular hybridization. Nucleic acid hybridization studies reveal that the origin of the SAIDS-D isolate may reside in Old World monkey (subfamily Colobinae) cellular DNA.

Acquired Immunodeficiency Syndrome↗
PubMed1984

Simian AIDS: isolation of a type D retrovirus and transmission of the disease.

A type D retrovirus related to but distinct from Mason-Pfizer monkey virus was isolated in vitro from the blood of two rhesus monkeys (Macaca mulatta) with simian acquired immunodeficiency syndrome (SAIDS). Three juvenile rhesus monkeys that were injected intravenously with tissue culture fluids containing this virus developed SAIDS after 2 to 4 weeks.

Acquired Immunodeficiency Syndrome↗
PubMed1984

Monoclonal antibodies to human colorectal tumor-associated antigens: improved elicitation and subclass restriction.

Monoclonal antibodies to tumor-associated antigens (TAA) of human colorectal cancer were elicited using immunosorbents of lectins combined with peripheral protein extracts of xenografted colon adenocarcinoma. This method of immunization was compared with whole cells from surgical specimens and to crude membranes from xenografted tumors. The immunosorbent immunogens were superior to the other immunogens in three ways: (1) the number of hybrids reactive with colon tumor cells or extracts, but not with lymphoid cells or extracts, (2) the number of stable hybrids after cloning, and (3) the number of hybridoma clones reactive with tissue sections of colon tumors, but not normal colonic mucosa. In addition, lectin immunosorbents elicited primarily IgG antibodies, especially IgG3, with almost 50% of the clones of interest reacting to seemingly less immunogenic glycoproteins. The improved elicitation of monoclonal antibodies to TAA by the use of lectin immunosorbents and peripheral protein extracts has considerable potential for generating reagents useful in diagnosis and therapy of human tumors.

Animals↗
PubMed1984

Molecular biological characterization of a highly leukaemogenic virus isolated from the mouse. IV. Viral proteins.

The proteins of a highly leukaemogenic murine virus (DMBA-LV) endogenous to the CFW/D mouse have been characterized. This virus does not contain ecotropic, xenotropic or polytropic type C retroviruses capable of replicating in established tissue culture cell lines. Analysis of the viral proteins indicated that proteins characteristic of both type C and type B retroviruses were present. All the proteins characteristic of a competent, mature type B retrovirus, such as the murine mammary tumour virus, were present in the virions and were expressed at high levels in a virus-producing thymic lymphoma cell line. Type C internal structural proteins were detected in the virus and cells producing virus. Type C envelope protein was detected at very low levels in both the virions and the virus-producing tumour cell lines. Chymotryptic polypeptide profiles of this gp70 indicated similarity with the envelope glycoproteins characteristic of xenotropic and recombinant type C retroviruses.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1982

Processing and amino acid sequence analysis of the mouse mammary tumor virus env gene product.

The envelope proteins of mouse mammary tumor virus (MMTV) are synthesized from a subgenomic 24S mRNA as a 75,000-dalton glycosylated precursor polyprotein which is eventually processed to the mature glycoproteins gp52 and gp36. In vivo synthesis of this env precursor in the presence of the core glycosylation inhibitor tunicamycin yielded a precursor of approximately 61,000 daltons (P61env). However, a 67,000-dalton protein (P67env) was obtained from cell-free translation with the MMTV 24S mRNA as the template. To determine whether the portion of the protein cleaved from P67env to give P61env was removed from the NH2-terminal end of P67env and as such would represent a leader sequence, the NH2-terminal amino acid sequence of the terminal peptide gp52 was determined. Glutamic acid, and not methionine, was found to be the amino-terminal residue of gp52, indicating that the cleaved portion was derived from the NH2-terminal end of P67env. The NH2-terminal amino acid sequences of gp52's from endogenous and exogenous C3H MMTVs were determined though 46 residues and found to be identical. However, amino acid composition and type-specific gp52 radioimmunoassays from MMTVs grown in heterologous cells indicated primary structure differences between gp52's of the two viruses. The nucleic acid sequence of cloned MMTV DNA fragments (J. Majors and H. E. Varmus, personal communication) in conjunction with the NH2-terminal sequence of gp52 allowed localization of the env gene in the MMTV genome. Nucleotides coding for the NH2 terminus of gp52 begin approximately 0.8 kilobase to the 3' side of the single EcoRI cleavage site. Localization of the env gene at that point agrees with the proposed gene order -gag-pol-env- and also allows sufficient coding potential for the glycoprotein precursor without extending into the long terminal repeat.

Amino Acid Sequence↗