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Biomedical subjects

H Petry

Publications and source records attributed to H Petry.

At least 55 records · Page 3Linked to original sources
PubMed1994

Persistent infection with SIVmac chimeric virus having tat, rev, vpu, env and nef of HIV type 1 in macaque monkeys.

A chimeric human and simian immunodeficiency virus carrying the tat, rev, vpu, env, and nef genes of human immunodeficiency virus type 1 was generated. The chimeric virus, NM-3n, grew competently in peripheral blood mononuclear cells from cynomolgus monkeys like the parental SIVmac. Two cynomolgus monkeys and one rhesus monkey inoculated with NM-3n raised antibodies to SIVmac Gag and HIV-1 Env. The antibodies raised in the cynomolgus monkeys persisted for at least 1.7 years. The antibodies contained virus neutralizing activity not only to the original chimeric virus but also to the parental HIV-1. Infectious viruses were isolated from one of the cynomolgus monkeys 37 and 63 weeks after inoculation and from the rhesus monkey continuously from 6 weeks after infection onward. The recovered virus maintained its chimeric structure but included several clones with mutations in the env V3 region. When the recovered virus was inoculated to another rhesus monkey, no difference in the frequency of virus recovery was seen from the originally infected monkeys. These carrier monkeys have so far shown no sign of the disease.

Animals↗
PubMed1994

Early helper T-cell dysfunction in simian immunodeficiency virus but not in human immunodeficiency virus type-2-infected macaques.

Both naive and vaccinated macaques acquired a virus-specific proliferative helper T-cell reactivity in response to infection with the nonpathogenic human immunodeficiency virus type 2 (HIV-2). In contrast, macaques infected with the pathogenic simian immunodeficiency virus of the macaque strain (SIVmac) did not develop a helper T-cell response. Furthermore, a vaccine-induced preexisting T-cell reactivity was abrogated after SIVmac infection in vaccine failures. These differences may reflect the different pathogenicity of the two closely related viruses.

AIDS Vaccines↗
PubMed1994

Increasing melanoma incidence: putatively explainable by retrotransposons. Experimental contributions of the xiphophorine Gordon-Kosswig melanoma system.

The worldwide accelerating increase of neoplasia in humans is difficult to explain. We use the Xiphophorus tumor model to approach this problem by melanoma provocation with X-rays. Melanoma develops following inappropriate expression of x-erb B-conducted developmental genes and their controllers. These oncodeterminants are inherited according to Mendelian rules. We detected a new type of oncodeterminants that, following a single treatment of embryos with X-rays, generates a self-generating non-Mendelian melanoma transmission and accelerating increase of its incidence in succeeding generations (e.g., 0-->18-->33-->52%). To localize these oncodeterminants, we crossed nonirradiated fish having half of their chromosomes irradiated with nonirradiated fish having none of, half of, or all of their chromosomes irradiated. Because tumor rate and expression in the following generations correspond to the rates of treated chromosomes, we conclude that the new oncodeterminants are distributed over the chromosomes of the fish, where they may increase in the changing generations. By means of xiphophorine-specific retroviral DNA, we isolated two retrotransposons that behave hereditarily like the new transgenerational oncodeterminants. Sequence analysis revealed three ORFs flanked by LTRs containing motives of regulatory sequences typical for known retroviral and retrotransposal LTRs. Pol- and env-resembling sequences are lacking. Southern and in situ hybridization showed their multiple and repetitive nature distributed throughout the chromosomes and indications for their capability to increase in number without further treatment. Their transcripts are expressed in concert with those of most of the other known xiphophorine tumor determinants. Their expression is extremely high in cell cultures from tumorous embryos derived from ancestors treated as embryos with X-rays.

Animals↗
PubMed1994

Variability of the env gene in cynomolgus macaques persistently infected with human immunodeficiency virus type 2 strain ben.

The sequence variability of distinct regions of the proviral env gene of human immunodeficiency virus type 2 strain ben (HIV-2ben) isolated sequentially over 3 to 4 years from six experimentally infected macaques was studied. The regions investigated were homologous to the V1, V2, V3, V4, V5, and V7 hypervariable regions identified in the env genes of HIV-1 and simian immunodeficiency virus SIVmac, respectively. In contrast to findings with HIV-1 and SIVmac, the V1- and V2-homologous regions were found to be highly conserved during the course of the HIV-2ben infection in macaques. The V3-homologous region showed a degree of variation comparable to that of HIV-1 but not of SIV. In the V4-, V5-, and V7-homologous regions, mutation hot spots were detected in most reisolates of the infected monkeys. Most of these mutations occurred during the first 10 weeks after infection. After 50 weeks, new mutations were rarely detected. At most mutation sites, a dynamic equilibrium between the mutated viral isotype and the infecting predominant wild type was present. This equilibrium might prevent an accumulation of mutations in isolates later in the course of infection.

Amino Acid Sequence↗
PubMed1994

Immunization with virion-derived glycoprotein 130 from HIV-2 or SIV protects macaques against challenge virus grown in human or simian cells or prepared ex vivo.

We have compared in the macaque model the efficacy of the virion-derived glycoprotein of HIV-2ben (HIV-2 gp130) with that of SIVmac251/32H (SIV gp130). The latter vaccination trial was in part combined with vaccinia virus (VV) priming. Both antigen preparations induced a strong humoral, but a weak cellular, immune response. The first challenge was performed with autologous virus grown on a human T cell line. More than 50% of the monkeys immunized with HIV-2 gp130 (five of nine) and 63% of the monkeys immunized with SIV gp130 (five of eight) were protected. All such protected animals received one or two booster immunizations before they were rechallenged either with heterologous HIV-2SBL6669 grown on monkey peripheral blood mononuclear cells or with an ex vivo stock of SIVmac251/32H prepared from the spleen of an SIV-infected macaque and not passaged in vitro. Immunization with HIV-2 gp130 did not protect against the second challenge, but one animal showed limited infection as indicated by positive PCR only. Challenge of the SIV gp130-immunized monkeys with the spleen-derived virus led to infection of three animals; remarkably, one of these was only PCR positive. Two animals were completely protected. Thereby we can exclude the influence of cellular proteins on protective immunity. Priming with VV was not superior to immunization with gp130 alone. Neither at the first nor at the second challenge were the virus-specific humoral and cellular immune responses of the vaccinees clearly correlated with protection. However, neutralizing antibodies may have been important in the SIV gp130-immunized animals at first challenge.

AIDS Vaccines↗
PubMed1993

Protection of cynomolgus macaques (Macaca fascicularis) against infection with the human immunodeficiency virus type 2 strain ben (HIV-2ben) by immunization with the virion-derived envelope glycoprotein gp130.

We have investigated the efficiency of a subunit vaccine consisting of native gp130 micelles of HIV-2ben mixed with keyhole limpet hemocyanin (KLH). Over a period of 52 weeks, nine cynomolgus monkeys (Macaca fascicularis) were immunized with seven intramuscular injections of gp130-KLH, equivalent to a total of about 1.1 mg of purified gp130 per animal. The first three applications were formulated in Freund's incomplete adjuvant. Because of the effects of Freund's incomplete adjuvant, aluminum hydroxide was used for the four subsequent immunizations. Each of the nine vaccinated animals along with six controls were challenged with 10 monkey infectious doses (MID50) of live HIV-2ben. At the time of challenge, the vaccinees had developed anti-gp130 titers ranging from 1 to 1.5 x 10(5). Four animals exhibited neutralizing antibodies. After iv challenge with 10 MID50 of HIV-2ben the nine vaccinees showed neither a secondary immune response nor a transient viremia. However, in four of the nine immunized animals proviral sequences were sporadically detected by polymerase chain reaction (PCR) and one of these four animals developed cytotoxic T lymphocytes. All six control animals developed a primary antibody response to HIV-2ben and became PCR positive. Four animals showed cytotoxic T cell activity and two developed a transient viremia. The five vaccinees with no sign of virus infection were reimmunized once and challenged with 10 MID50 of the heterologous virus HIV-2SBL-6999. Four weeks later all animals were PCR positive. A naive control animal and four of the vaccinees showed primary or secondary antibody responses and transient viremia. One of the revaccinated animals did not become viremic, and viral antibodies did not increase.

AIDS Vaccines↗
PubMed1993

Protection of monkeys by a split vaccine against SIVmac depends upon biological properties of the challenge virus.

OBJECTIVE: To investigate the role of the anti-cellular immune response in the protection of rhesus macaques against infection with the simian immunodeficiency virus SIVmac. To determine the biological differences between SIV challenge stocks grown either on human T-cell lines or on monkey peripheral blood mononuclear cells (MPBMC). DESIGN: A protective SIVmac split vaccine was administered to rhesus macaques and their anti-, B- and T-cell response monitored. Vaccinees and controls were challenged with SIVmac grown either on human or on monkey cells. The in vivo replication rate of, and the immune response to, the two viruses was compared. METHODS: Five rhesus macaques were immunized with a total of 2 mg each of purified SIVmac251/32H grown on the human C8166 T-cell line. The antibody and proliferative T-cell responses were evaluated by enzyme-linked immunosorbent assay and T-cell proliferation assay, respectively. Four protected animals and four controls were reboosted and challenged with MPBMC-grown SIVmac251 (SIVmac251/MPBMC). Cell-free virus load was determined by titration of plasma for SIV infectivity on C8166 cells and antigen with a core antigen capture assay. RESULTS: Protection from virus challenge with C8166-grown SIVmac251/32H or SIVmac251/MPBMC did not correlate with anti-cellular antibodies or proliferative T-cell reactivities. Control animals infected with SIVmac251/MPBMC showed high persistent antigenaemia and high plasma virus titres. Both were absent in controls infected with complement C8166-grown SIVmac251/32H. Whereas the latter always seroconverted against the full panel of viral polypeptides, SIVmac251/MPBMC-infected animals showed a drastically decreased antibody response. CONCLUSIONS: Neither the antibody nor the proliferative T-cell response to SIVmac correlates with protection from virus challenge. In contrast to SIVmac251/32H grown on C8166 cells, the MPBMC-grown challenge virus SIVmac251 appears to belong to the 'rapid-high' phenotype, possibly explaining the lack of protection against this SIV.

Animals↗
PubMed1993

Differences in the B and T cell immune response to the envelope glycoprotein 130 (gp130) of the macaque strain of simian immunodeficiency virus (SIVmac), induced by immunization of rhesus macaques with virus-derived or vaccinia virus-expressed gp130.

Rhesus macaques were immunized with purified virus-derived simian immunodeficiency virus of macaques (SIVmac) 251/32H glycoprotein 130 (gp130) or primed with recombinant vaccinia virus (VV) expressing the env gene of the SIVmac BK28 clone and boosted subsequently with virus-derived gp130. High antibody titres of at least 10(4) against recombinant gp140 were induced with both vaccines. Analysis of the antibody specificity with a peptide ELISA revealed that different linear epitopes were recognized after administration of virus-derived gp130 compared with those after priming with VV. Antibodies to some epitopes (peptides 10 and 49), which were also found in SIV-infected animals, were induced with both vaccines, whereas antibodies to other regions were induced by only one vaccine preparation. The analysis of the helper T cell response revealed a poor immunogenicity of the virus-derived gp130, whereas priming with VV induced a considerable helper T cell activity in all three vaccinees after the second VV infection. Using synthetic peptides, several epitopes were identified. Our observations show that immunization with a virus-derived gp130 or live recombinant VV induces a considerably different antibody and helper T cell response. These differences in immunogenicity might have important implications for further vaccine development.

Amino Acid Sequence↗
PubMed1992

Immunization with tween-ether-treated SIV adsorbed onto aluminum hydroxide protects monkeys against experimental SIV infection.

In order to examine the efficiency of an AIDS vaccine potentially acceptable for human use we have investigated a split vaccine. Since such vaccines are safe and efficient, they have been in use for many years to protect man against enveloped RNA viruses, e.g., influenza and measles. Seven rhesus monkeys were immunized at Week 0, 4, 8, and 16 by im injection of 2 ml of vaccine containing 140 micrograms of Tween-ether-disrupted SIVmac251/32H adsorbed onto aluminum hydroxide. The immunized animals and three nonvaccinated control monkeys were challenged 2 weeks after the last immunization by iv injection of 10 to 50 minimal monkey infectious doses of SIVmac251/32H. Four of seven immunized animals did not show any signs of virus replication and therefore appeared to be protected. Nonvaccinated control animals and the vaccine failures showed a rise in their urinary neopterin concentrations 1 to 2 weeks after infection. At the end of the second week and thereafter, cocultures and polymerase chain reaction of their peripheral blood lymphocytes were positive. After the challenge, control animals and infected vaccinees showed a primary or secondary antibody response while antibody titers declined in virus-negative animals. Specific cytotoxic T-lymphocytes were not present prior to challenge, but were present in some animals thereafter. Therefore, these seem to reflect a response to viral replication rather than to immunization. Prior to challenge the CD4-positive lymphocytes of the peripheral blood of the four virus-negative animals only proliferated after exposure to the immunizing antigen. Thus, this reaction appears to predict protection.

Adjuvants, Immunologic↗
PubMed1992

Isolation and characterization of a retrovirus from the fish genus Xiphophorus.

A cell line (BsT) established from neoplastic embryonal tissues of the platyfish (Xiphophorus maculatus) released spontaneously retrovirus-like particles. The particles have a buoyant density of 1.16 g/ml, a mean diameter of 100 nm and the morphology of immature retroviruses. The particle-associated proteins p70, p65, and p28 react with an antiserum directed against the major internal feline leukemia virus structural protein p27. The particles are associated with a reverse transcriptase. The purified enzyme has a molecular weight of about 70 kDa and prefers the template primers poly(rA):oligo(dT), poly(dC):oligo(dG), and poly(rC):oligo(dG) in the presence of Mn2+. The enzyme activity is inhibited by antibodies directed against the reverse transcriptase of feline leukemia virus and simian sarcoma virus. The particles contain a ribonucleic acid of about 70 S. In an endogenous reverse transcriptase reaction nucleic acids in the range of 0.2 to 0.4 kb were synthesized. In Northern blots with these nucleic acids as probe, three transcripts of about 8.5, 4.2, and 1.5 kb were detected in BsT cells. Southern blot analysis with the same probe demonstrates related sequences in the DNA of BsT cells and the platyfish and swordtail (Xiphophorus helleri). Hybridization experiments with the LTR-gag region of the feline leukemia virus show homologous sequences in the Xiphophorus genome.

Animals↗
PubMed1992

Immunization of rhesus monkeys with high- and low-dose Tween-ether-disrupted SIVMAC.

Two vaccine trials were conducted with low- and high-dose purified Twen-ether-treated SIVmac adsorbed onto aluminum hydroxide using rhesus macaques. In the first experiment 7 macaques were immunized with a total amount of 560 micrograms protein and 3 animals served as controls. After the immunization period the vaccinees exhibited ELISA titers up to 1:1280 and 5 immunized animals showed an antigen-specific proliferative response. After the virus challenge the 3 control animals and 3 vaccinees became infected. Four of the infected animals developed a cytotoxic T-cell response beginning 8 weeks postchallenge. The 4 protected animals were rechallenged 16 weeks later and all became infected. For the high-dose experiment 5 immunized animals receiving 2 mg of antigen and 2 control animals were used. The ELISA titers of the vaccinees reached 1:20480 and 4 animals exhibited an antigen-specific proliferative response. In response to virus challenge the 2 control and 1 immunized animal became infected. From these data it can be concluded that the high-dose immunization scheme elicited higher antibody titers and increased the fraction of protected animals.

Adjuvants, Immunologic↗
PubMed1992

Potential significance of the cellular immune response against the macaque strain of simian immunodeficiency virus (SIVMAC) in immunized and infected rhesus macaques.

The cellular immune response of seven rhesus macaques immunized with Tween-ether-treated macaque strain of simian immunodeficiency virus (SIVMAC) and three non-vaccinated control animals was investigated. Immunization elicited antigen-specific proliferating CD4+ cells in five of seven monkeys. Proliferating T cells were found in all animals protected from a first virus challenge. Cytotoxic T lymphocytes (CTLs) were not induced by the immunization. After the second challenge, the four formerly protected animals became infected, despite a strong proliferative CD4+ cell activity in three of them. All animals lost their proliferative activity 2 weeks after infection. After the first challenge four of the six infected animals exhibited a CTL response and after the second challenge, one of four newly infected macaques acquired a CTL response. The five animals with a CTL activity against SIVMAC proteins were protected from severe thrombocytopenia, which appeared in the five CTL-negative animals after infection. Our data show the induction of proliferative T cells by immunization with soluble SIVMAC antigen. This T cell reactivity was found in all animals protected from the first virus challenge, but did not confer protection from the second challenge. Interestingly, the proliferative T cell reactivity disappeared 2 weeks after virus infection. Furthermore a CTL response against viral proteins seems to protect infected animals from severe thrombocytopenia which is an early sign of AIDS in monkeys.

Animals↗
PubMed1991

[Feeding activity, spontaneous activity and body core temperature of saddle-back tamarins (Saguinus fuscicollis)].

Eating behaviour and spontaneous activity (videometry) as well as deep body temperature (radiotelemetry) of 3 adult Saddle Back Tamarins (Saguinus fuscicollis) were investigated (singly housed, environmental temperature 28 degrees C, relative air humidity 60%, light 6:00-18:00 h, drinking-water and pelleted colony diet ad lib.). The experimental animals (1 female, 2 males; 3-8 years old), born in captivity, showed only some slight individual differences within their inborn species pattern, with regard to the 3 measured parameters. The monkeys were, like wild-living individuals, strictly light-active. They moved in the day-time nearly uninterrupted without special rhythm and slept remarkably deep through the whole night. Food intake occurred during the whole day with varying intensity. The body temperature of the 3 monkeys showed individual daytime-means between 38.8-39.9 degrees C, whereby the temperature fluctuated dependent on their moving activity with a range of about +/- 0.5 degrees C. At night the body temperature of the animals averaged between 35.9-36.6 degrees C.

Animals↗
PubMed1990

Detection of RNA-dependent DNA polymerase activity in the Xiphophorus melanoma system.

DNA polymerases have been isolated from muscle and melanoma tissues of Xiphophorus, which are similar to retroviral RNA-dependent DNA polymerases as they prefer RNA to DNA templates. They appear to associate with submicroscopic structures which exhibit a density of about 1.13 g/ml after sucrose-density-gradient centrifugation. The RNA-dependent-DNA-polymerase-like enzymes could be separated from the DNA-dependent DNA polymerases by DEAE-cellulose chromatography. Further purification on phosphocellulose revealed that the muscle enzyme eluted at the void volume and at about 0.6 M KCl, whereas most of the melanoma enzyme eluted at 0.1 M KCl. Comparison of the template primer specificities of the muscle and melanoma enzymes with those of known DNA polymerases showed obvious similarities to the RNA-dependent DNA polymerase isolated from Rous sarcoma virus.

Animals↗
PubMed1990

[Radiotelemetric studies of the body temperature of white-tufted monkeys (Callithrix jacchus)].

A newly developed telemetry system was used to study deep body temperature (BT) of two adult male common marmosets (Callithrix jacchus). The BT-curves of both monkeys showed a similar clear circadian rhythm with a range up to 3.5 degrees C. At environmental temperature of 28 degrees C (ET) the BT of the monkeys varied in the daytime dependent on their spontaneous activity, with little individual differences between 37.5 degrees C and 39.3 degrees C; at night the BT of the remarkably deeply-sleeping animals decreased to an average at 35.8 degrees C. Elevating ET up to 30 degrees C effected an increase of BT by 0.6 degrees C, both during day and night. On the contrary, reducing ET to 24 degrees C the BT increased only at night, by 0.2 degrees C at ad libitum food intake and 1.0 degrees C at fasting. Measurements of BT by inserted rectal thermometer caused, compared with telemetry, an average at 0.4 degrees C higher values.

Animals↗