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Biomedical subjects

G Hunsmann

Publications and source records attributed to G Hunsmann.

At least 181 records · Page 10Linked to original sources

Long-term persistent infection of macaque monkeys with the simian immunodeficiency virus.

Juvenile rhesus macaques 6 to 18 months of age were experimentally infected by intravenous inoculation with the simian immunodeficiency virus (SIV), the T cell-tropic retrovirus of monkeys related to the human acquired immunodeficiency syndrome (AIDS) virus HIV. The SIV used for inoculation was grown either in normal human peripheral blood lymphocytes in the presence of interleukin 2 or in the human tumour cell line HUT-78. Eight of the macaques died 129 to 352 days post-inoculation with a variety of clinical and pathological findings paralleling those of AIDS in humans. However eight other animals became persistently infected for prolonged periods; these eight macaques remained alive at 537 and 820 days post-inoculation despite persistent lymphadenopathy and our continued ability to isolate SIV. The ability of these monkeys to survive infection correlated directly with the strength of their antibody response to SIV. Infection was also established in macaques using approximately 100 tissue culture infectious doses of HUT-78-grown SIV. There was no correlation between the dose of virus inoculum and either the strength of the antibody response or clinical outcome. These results demonstrate that SIV infection of macaques can be used not only to study acute AIDS but also to mimic the long-term persistent infection seen in carriers of HIV.

Acquired Immunodeficiency Syndrome↗

Synthetic vaccines against Friend murine leukaemia virus-induced erythroleukaemia: in vivo and in vitro studies with synthetic oligopeptides and sequence-specific antisera.

Biological activities of antisera against synthetic oligopeptides were examined. The peptide antisera were directed against amino acids 6 to 12 (pep1), 124 to 131 (pep2), 256 to 262 (pep3), 283 to 290 (pep4) and 434 to 441 (pep5) of the viral envelope glycoprotein (gp70). Peptide-specific antisera did not neutralize viral infectivity. However, antibodies to pep4 and pep5, which bound to the hydrophobic part of gp70, mediated the complement-dependent lysis of Friend murine leukaemia virus (FLV)-infected cells. STU mice were immunized against FLV-induced erythroleukaemia with synthetic oligopeptides. Vaccines containing only one of these peptides (single-peptide vaccines) as well as multi-peptide vaccines containing pep1, -4, -5 or pep1, -2, -3, -4, -5 were used. Whereas the immunizations with single-peptide vaccines did not protect the immunized mice from FLV-induced erythroleukaemia, multi-peptide vaccines enhanced the survival rate and incubation period after FLV challenge. These results revealed that immunological reactions distinct from neutralizing antibodies can be evoked by immunization with synthetic peptides and can confer limited protection against FLV-induced erythroleukaemia.

Amino Acid Sequence↗

Inhibition of human immunodeficiency virus type I reverse transcriptase by suramin-related compounds.

Ninety analogues of suramin have been examined for their ability to inhibit the exogenous reverse transcriptase (RT) of human immunodeficiency virus type I (HIV-I). Of these compounds, 57 inhibited the poly(rC).oligo(dG)-dependent RT activity. Three classes of dose-response curves could be discriminated. Allocation of a compound to one class did not correspond with obvious structural features. Twenty-four substances were superior to suramin in our RT inhibition assay. The RT-inhibitory activity of these compounds did not correlate with their effect against filariae or trypanosomes. Preliminary antiviral evaluation in susceptible human T cells inoculated with HIV-I demonstrated in vitro therapeutic efficacy for some compounds with lower drug-related cellular toxicity than suramin. Certain structural features relevant for the RT-inhibitory effect of these compounds were recognized. Predictions are made for the design of more effective RT inhibitors. Such compounds will help to understand the molecular mechanism of reverse transcription and might be useful in the therapy of retroviral infections.

Cell Line↗

Seroepidemiology of human immunodeficiency virus in Africa.

Serum samples from 6015 African subjects without symptoms of the acquired immune deficiency syndrome (AIDS) or contact with the disease were examined for antibodies to the human immunodeficiency virus by a combination of an enzyme linked immunosorbent assay and radioimmunoprecipitation (2567 samples) or by immunofluorescence (3448 samples). Serum samples had been collected between 1976 and 1984 in Senegal (n = 789), Liberia (935), Ivory Coast (1195), Burkina Faso (299), Nigeria (536), Gabon (1649), Zaire (15), Uganda (164), and Kenya (433). Only four samples contained antibodies. Three of these were from attenders at the Lambarene clinic in Gabon and one from a villager in Senegal. By contrast, two out of six AIDS suspects from Guinea-Bissau, all 13 patients with AIDS from Kinshasa (Zaire), and two out of three of their contacts were seropositive, all these specimens having been collected in 1985. These data show that fewer than one in a 1000 subjects were seropositive for AIDS at the time of sampling before 1985 and do not support the hypothesis of the disease originating in Africa.

Africa↗

Structural analysis of p19 and p24 core polypeptides of primate lymphotropic retroviruses (PLRV).

Core polypeptides of primate lymphotropic retroviruses (PLRV) have very similar molecular weights. To discriminate between individual PLRVs we have compared two-dimensional tryptic peptide maps of 125I-labeled core polypeptides p19 and p24 of 11 isolates originating from humans and six simian species. Peptide maps showed homologies between all the simian viruses and the human isolates, but they were completely different from those of human T-cell leukemia virus type III (HTLV-III). In general p24s are more conserved than p19s. According to the relationship of their peptide maps we have classified the PLRVs into three groups, the human and chimpanzee isolates, macaque viruses, and green monkey virus.

Animals↗

Subregions of a conserved part of the HIV gp41 transmembrane protein are differentially recognized by antibodies of infected individuals.

A 240-bp DNA fragment encoding a peptide, designated ENV(80), homologous to a conserved part of the gp41 transmembrane glycoprotein of human immunodeficiency virus (HIV) was chemically synthesized and inserted into different plasmid expression vectors. Escherichia coli transformants containing these plasmid constructs produced upon induction high amounts of either an ENV(80) peptide of relative molecular mass (Mr) of 10,000 or the same ENV(80) peptide N-terminally fused to E. coli chloramphenicol acetyltransferase (CAT) or to mouse dihydrofolate reductase (DHFR) having Mr of 36,000 and 31,000 respectively. All polypeptides containing the ENV(80) sequences were strongly reactive with antibodies present in sera from AIDS virus-infected individuals, but not with control sera. The strategy of gene assembly allowed the expression of ENV(80) subfragments fused to DHFR. The serodiagnosis of 15 positive sera by Western blot analysis using these bacterially synthesized ENV(80) subfragments revealed the presence of several immunoreactive epitopes on the 80-amino acid polypeptide which were recognized differently by the various patients.

Acquired Immunodeficiency Syndrome↗

Shedding and interspecies type sero-reactivity of the envelope glycopolypeptide gp120 of the human immunodeficiency virus.

Two glycopolypeptides with molecular weights 160,000 and 120,000 (gp120) are regularly recognized by human immunodeficiency virus (HIV)-specific antisera in lysates of cells persistently infected with HIV. In the present study, gp120 was characterized as the major envelope glycopolypeptide of HIV. Gp120 was identified as the external viral glycoprotein by radiosequencing and by its presence in purified virus. However gp120 was predominantly shed as a soluble protein into the culture fluid. Furthermore gp120 was precipitated by sera from horses infected with equine infectious anaemia virus (EIAV), but not by sera from uninfected animals. This may indicate conserved epitopes common to the envelopes of HIV and EIAV.

Antibodies, Viral↗

Quantification of infection and neutralization of murine leukaemia virus by a microtitre enzyme-linked immunosorbent assay.

We have developed an enzyme-linked immunosorbent assay for murine leukaemia virus using methanol-fixed cells as antigen. Specific antisera clearly recognized viral antigens within cells adherent to the microtitre plates. This test was used to quantify infection, to monitor virus multiplication and to demonstrate virus neutralization by antisera. The ELISA was as sensitive as, and faster and easier to perform than, the XC plaque assay and could even quantify large amounts of virus. It can easily be adapted for assaying other viruses.

Animals↗

Immunoprevention of Friend leukaemia virus-induced erythroleukaemia by vaccination with aggregated gp70.

Vaccines prepared from Friend leukaemia virus envelope and core polypeptides were compared for their efficiency in preventing erythroleukaemia in mice. High doses (100 micrograms) of gp85, the micellar complex of the envelope polypeptides gp70 and p15E, completely protected STU mice. The same dose of purified gp70 still protected about 80% of the animals, while p15E did not affect the cumulative mortality. The internal viral polypeptide p30 was ineffective. Serological examination indicated that immunity against death from leukaemia was mediated by specific antibodies. These leukaemia-preventing antibodies were predominantly induced by immunization with the gp70 env gene product, since p15E showed only minor protection. Glycoprotein gp70, however, was more effective when given as the gp85 micellar complex. An even more potent vaccine was obtained when gp70 was coupled to keyhole limpet haemocyanin (KLH) by glutaraldehyde. Ten micrograms gp70 coupled to KLH was enough to save more than 90% of Friend leukaemia virus-infected mice from erythroleukaemia. KLH may also be a suitable experimental carrier for subunits of gp70 or synthetic oligopeptides for viral vaccines.

Animals↗

Correlation of immune defects in hemophilia with HTLV-III antibody titers.

Of 170 hemophilia patients, 22% had high-titer, 29% had low-titer, and 49% had no antibodies against HTLV-III. The strength of HTLV-III antibodies was correlated significantly with a decreased OKT4/T8 ratio (p less than 0.0005), decreased in vitro response to pokeweed mitogen (p less than 0.025), and elevated serum neopterin (p less than 0.05) and serum IgG (p less than 0.0005). The fraction of patients with abnormal immunological findings was consistently greater among patients with high-titer than among patients with low-titer HTLV-III antibodies. Testing these immunological parameters may be useful for monitoring the breakdown of immune functions leading to AIDS.

Acquired Immunodeficiency Syndrome↗

Lymphadenopathy and antibodies to HTLV-III in homosexual men. Clinical, laboratory and epidemiological features.

The study provides information on the epidemiology of HTLV-III infection and the lymphadenopathy syndrome (LAP) in 374 German homosexual men. Sexual contacts in the USA and rectal enemas before receptive anal intercourse are the main risk factors associated with virus transmission. HTLV-III seropositivity is significantly correlated with LAP. Prominent clinical signs are infrequent. Immunological and haematological abnormalities are prevalent, and the retrovirus infection is frequently associated with serological markers of other viruses (hepatitis B, herpes group viruses). Lymphadenopathy as a manifestation of HTLV-III infection is discussed within the context of AIDS-related disorders.

Acquired Immunodeficiency Syndrome↗

[Epidemiology of AIDS].

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Acquired Immunodeficiency Syndrome↗