Search PubMed⌕ Search

Biomedical subjects

R Kurth

Publications and source records attributed to R Kurth.

At least 145 records · Page 8Linked to original sources
PubMed1989

Retroviruses and malignant lymphoma.

Retroviruses are single stranded RNA viruses that possess a unique enzyme, reverse transcriptase. This enzyme facilitates the synthesis of double stranded DNA intermediates able to integrate into the genome of the host cell. Although primarily a means of remaining latent, this integration can have the effect of transforming the cell to malignant growth, either by activation of growth control genes in cis or trans, or by insertion of an integrated oncogene. Malignant lymphomas caused by retroviruses occur in animals from mice to man, and have increasing economic and clinical significance. HTLV-1 is the causative agent of adult T-cell leukemia/lymphoma which is endemic in certain discrete locations of the world and has been implicated in a variety of other disorders. The fact that the virus seems to be spreading through groups of intravenous drug abusers in much the same way as the AIDS virus is a cause for concern.

Animals↗
PubMed1989

HIV and HIV-infected cells differentially activate the human complement system independent of antibody.

The human retroviruses HTLV-I and HIV-I have previously been shown not to be lysed by human serum. An interaction between HIV and the complement system, however, has not been investigated in any detail. In this report we show that purified HIV as well as HIV-infected cells activate the complement system. In the case of virus-infected cells this activation is mediated by the alternative pathway of complement, whereas the classical pathway seems to be in operation for the triggering of the complement system by purified virus and recombinant envelope glycoprotein (gp 160). We demonstrate that this leads to the deposition of C3b and/or C3bi on the surface of infected cells. But the HIV-infected cells are not lysed by human complement. C3 fragments deposited on the surface of HIV-infected cells are capable of mediating immune adherence to complement receptor-bearing cells, such as human erythrocytes and phagocytes. Whether this might have an influence on infectivity of HIV for certain cells bearing complement receptors has yet to be shown.

Cell Line↗
PubMed1989

Isolation of human immunodeficiency virus-related simian immunodeficiency viruses from African green monkeys.

We have isolated lentivirus strains that are related to the human immunodeficiency virus (HIV) from African green monkeys (Cercopithecus aethiops; AGM). Although immunologically related, these SIVagm are clearly distinct from other simian immunodeficiency virus (SIV) isolates, including isolates from Macaca mulatta (SIVmac) or even from other AGM. The SIVagm strains described in this communication grow well in a limited number of human T-lymphoma lines. Virus density, morphology, and reverse transcriptase activity are characteristic of the lentivirus group. SIVagm exhibits the following pattern of major virus proteins: p18, p28, gp45, p64, gp140. They appear to bind to the target cell via the CD4 or its primate analogue. Four virus isolates have already been molecularly cloned for detailed genomic analysis and within this SIV agm group they exhibit the genomic variability that is typical of lentiviruses. AGMs infected with this virus apparently remain healthy and therefore SIVagm not only provides a virus model for vaccine studies but also allows investigation of the defense mechanisms (immunological and others) that keep the AGMs healthy. Furthermore, precise genomic analysis of these and other SIV strains will lead to a better understanding of the evolution and pathogenicity of human lentiviruses like HIV.

Animals↗
PubMed1989

Azidothymidine triphosphate is an inhibitor of both human immunodeficiency virus type 1 reverse transcriptase and DNA polymerase gamma.

The reverse transcriptase from human immunodeficiency virus type 1 was purified from the virus to near homogeneity. The enzyme was shown to possess both RNA-dependent and DNA-dependent DNA-synthesizing activity. Activated DNA as a heteropolymeric substrate was used as efficiently as was the homopolymeric substrate poly(rA)-oligo(dT). The Michaelis-Menten constants were determined for each of the four nucleotides needed to elongate a natural template primer. Azidothymidine triphosphate, a well-known inhibitor of the enzyme, inhibited the enzyme competitively with respect to dTTP and noncompetitively with respect to the other nucleotides. Azidothymidine triphosphate acted as an efficient inhibitor of cellular DNA polymerase gamma, whereas other enzymes of eucaryotic DNA metabolism, namely, DNA polymerase alpha-primase and DNA polymerase beta, were not inhibited. This finding may explain why some acquired immunodeficiency syndrome patients suffer side effects during azidothymidine therapy.

DNA Polymerase III↗
PubMed1989

Molecularly cloned simian immunodeficiency virus SIVagm3 is highly divergent from other SIVagm isolates and is biologically active in vitro and in vivo.

Simian immunodeficiency viruses have been isolated from African green monkeys originating from Ethiopia. A molecular clone, termed SIVagm3, was found to be highly divergent from SIVagmTYO-1 in terms of its restriction map and partial nucleotide sequence. A premature stop codon present in the transmembrane protein of SIVagm TYO-1 was absent in SIVagm3. SIVagm3 was biologically active in vitro and in vivo and displayed characteristics reminiscent of the wild-type virus. Biological activity was demonstrated by seroconversion of juvenile African green monkeys and Macaca nemestrina after inoculation. In contrast to antibody reactivity mainly directed against env proteins in naturally infected African green monkeys. African green monkeys and M. nemestrina infected with the cloned virus showed antibody reactivity directed against all major proteins as demonstrated by immunoblot analysis. The availability of a biologically fully competent molecular clone of SIVagm allows us now to address various pertinent questions in an animal model system which should help to understand features of human immunodeficiency virus infection in human beings.

Amino Acid Sequence↗
PubMed1988

B and T cell reactivities after immunization of macaques with HIV subcomponents.

A model system was established for studies of humoral and cellular immunity to human immunodeficiency virus (HIV) antigens after vaccination. Macaques (Macaca fascicularis) were immunized with purified HIV, an infected cell extract rich in gp120 or polypeptides of cloned genes representing parts of p24, gp41, and gp120. Western blot analysis best showed the appearance of antibodies to nucleocapsid proteins, and antibodies to higher molecular weight envelope glycoproteins were better demonstrated by radioimmunoprecipitation. With whole HIV, antibodies to p24 appeared first, and sometimes were the only ones to be demonstrable. Several immunizations with HIV or recombinant polypeptides were required to obtain antibodies to gp120, and the responses were weak. Although the envelope-specific response was weak, this was the only component that mediated neutralizing capacity. Escherichia coli-derived viral transmembrane polypeptide (g)p41 also had a poor immunizing effect. IgG synthesis from B cells in vitro was demonstrable to antigens and generally paralleled the antibody titers of sera after multiple immunizations. The HIV-specific lymphocyte proliferation response as measured by DNA synthesis was best seen with polypeptide p24-15, followed by the other antigens.

Animals↗
PubMed1988

Inhibition of HIV-1 RNA-dependent DNA polymerase and cellular DNA polymerases alpha, beta and gamma by phosphonoformic acid and other drugs.

Potential specific inhibitors of HIV RNA-dependent DNA polymerase (RDDP) were examined in an in-vitro test system containing purified HIV-1 RDDP, or functionally purified cellular DNA-dependent DNA polymerases alpha, beta and gamma. A wide variety of drugs were tested for their specific inhibitory activity against the viral enzyme to identify substances which, at the same concentration, did not inhibit the cellular DNA polymerases. Phosphonoformic acid and derivatives were found to be the most specific inhibitors, followed by chlortetracycline.

Antiviral Agents↗
PubMed1988

Reverse transcriptases from human immunodeficiency virus type 1 (HIV-1), HIV-2, and simian immunodeficiency virus (SIVMAC) are susceptible to inhibition by foscarnet and 3'-azido-3'-deoxythymidine triphosphate.

Reverse transcriptases from human immunodeficiency virus type 1 (HIV-1), HIV-2, and simian immunodeficiency virus (SIV) were investigated with respect to susceptibilities to the reverse transcriptase inhibitors foscarnet and 3'-azido-3'-deoxythymidine triphosphate (AZTTP). The different reverse transcriptases had the same sensitivity to foscarnet (50% inhibition at 0.10 to 0.16 microM). The Ki values for AZTTP were 0.01 to 0.02 microM for HIV-1 reverse transcriptase and 0.02 to 0.03 microM for HIV-2 and SIVMAC reverse transcriptases.

Animals↗
PubMed1987

Perspectives of HIV vaccine developments.

Human immunodeficiency virus type 1 (HIV-1) may enter the blood stream as free virus or via infected lymphocytes, which poses problems for vaccine development. The classical vaccine designs, attenuated, inactivated, or subunit vaccine will be discussed with regard to HIV. Development of a recombinant subunit vaccine appears to be the most promising approach. Forthcoming results from experiments involving inoculation of chimpanzees should allow evaluation of the feasibility of using a subunit vaccine based on the env-glycoprotein. Also the use of live recombinant vaccinia merits further investigation.

Animals↗
PubMed1987

Genome analysis and reverse transcriptase activity of human teratocarcinoma-derived retroviruses.

Five of five human teratocarcinomas cultured in vitro could be induced to synthesize retrovirus-like particles, albeit in extremely low amounts. The accumulation and purification of the human teratocarcinoma-derived retrovirus (HTDV) from one of these cell lines allowed characterization of its genomic material as high mol. wt. (60S) RNA. Partial purification of HTDV-associated RNA-dependent DNA polymerase (reverse transcriptase) has also been achieved. HTDVs are easily distinguishable from the exogenous human T-lymphotropic viruses and human immunodeficiency viruses by morphological, biological and immunological criteria.

Humans↗
PubMed1987

Characteristics of the specific cell-mediated immune response in human immunodeficiency virus infection.

The human immunodeficiency virus (HIV)-specific lymphocyte proliferation response was determined for 40 persons at different stages of HIV infection. The specific response to purified HIV virion antigens from strain HTLV-IIIB was poor, occurred in only 9 of the 40 subjects, was not improved with the addition of interleukin-2, and was more frequent in symptom-free individuals (46%) than in patients with lymphadenopathy syndrome (10%). Reactivity to subcomponent p24 was better than that to whole HIV; reactivity was present in five of six infected persons and increased with the addition of exogenous interleukin-2. Reactivities to subcomponents (g)p41 and gp120 were also measured. This is the first evidence of a specific cell-mediated immune response to HIV antigen in HIV-infected persons. Monkeys immunized with purified HIV or with purified p24 displayed cellular immunoreactivity both to whole HIV and to subcomponents. In contrast to the poor reactivity to HIV antigen, the lymphocytes of the patients had good specific cell proliferation responses to cytomegalovirus and herpes simplex virus challenge and a normal response to the addition of phytohemagglutinin. The results suggest a functional defect in peripheral lymphocytes of some HIV-infected individuals on the basis of their response to whole HIV antigen and a better response to gag protein.

AIDS-Related Complex↗
PubMed1987

[Retroviruses and the development of lymphoma].

Retroviruses are small, RNA-containing enveloped viruses which are widely distributed in nature. They exist in many animal species as well as in man. Exogenous virus strains are horizontally transmitted between individuals of a given species, like all other virus groups. Endogenous virus strains have managed some time during evolution to infect germ line cells like oocytes and spermatocytes and are thus transmitted vertically from parents to offspring. Several retrovirus strains possess oncogenes, i.e., acutely tumor-inducing genes. There are four human retrovirus strains so far. The initially discovered strain, HTLV-I, is accepted to be a co-factor in the development of an acute T-cell leukemia in adults. HTLV-II has repeatedly been isolated from cells of patients with hairy cell leukemia. Its etiological significance is unclear at present. HTLV-III/LAV-1, now designated HIV-1, is the causative agent of AIDS. HTLV-IV and LAV-2 are additional HIV-1 related strains and are supposed to cause AIDS as well. What is known about the pathogenicity of the human retrovirus strains will be discussed.

Acquired Immunodeficiency Syndrome↗