Biomedical subjects

Helmut Fickenscher

Publications and source records attributed to Helmut Fickenscher.

10 recordsLinked to original sources

PubMed2006

Seroprevalence of six different viruses among pregnant women and blood donors in rural and urban Burkina Faso: A comparative analysis.

A seroprevalence study was carried out of six different human pathogenic viruses, namely human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), human T-cell leukemia virus (HTLV), human herpesvirus type 8 (HHV-8), and dengue virus among pregnant women and blood donors from rural (Nouna) and urban (Ouagadougou) Burkina Faso, West Africa. A total of 683 samples from blood donors (n = 191) and pregnant women (n = 492) were collected from both sites and screened for the different virus infection markers resulting in the following prevalence values for Nouna or Ouagadougou, respectively: HIV 3.6/4.6, anti-HBV core (anti-HBc) 69.6/76.4, HBV surface antigen (HBsAg)14.3/17.3, HCV 2.2/1.5, HTLV 1.4/0.5, HHV-8 11.5/13.5, dengue virus 26.3/36.5. Individuals aged > or =25 years were more likely to be infected with HIV than those below 24 years (P < 0.05). Infection with HIV increased the likelihood of co-infection with other viruses, such as HHV-8, HBV and HTLV. Co-infection studies involving five viruses (HBV-HBsAg, HHV-8, HIV, HCV, and HTLV) showed that 4.8% (33/683) of the studied population were dually infected, with HBsAg+ HHV-8 (13/33), HBsAg+HIV (8/33) and HIV+HHV-8 (8/33) being the most common co-infections. Of the population studied 0.6% (4/683) was triply infected, the most common infection being with HBV+HIV+HHV-8 (3/4). There was no difference in the prevalence of HIV, anti-HBc, HBsAg, HCV, HTLV, and HHV-8 either among blood donors or pregnant women in urban or rural setting, while dengue virus prevalence was relatively lower in rural (26.3%) than in urban (36.5%) Burkina Faso.

Adolescent↗

PubMed2005

Recurrence of clinically significant hepatitis A following liver transplantation for fulminant hepatitis A.

BACKGROUND: We report hepatitis A virus (HAV) infection of a liver allograft following transplantation for fulminant liver failure due to HAV infection. This rare condition has been described in only three patients to date. After liver transplantation allograft function was good, but starting 80 days after transplantation, episodes of acute graft dysfunction were observed. OBJECTIVES: To elucidate the reason for acute hepatic dysfunction a large number of differential diagnoses were tested. RESULTS: HAV RNA was undetectable for more than 80 days after transplantation. Detection of genomic HAV RNA by RT-PCR in serum and stool at the time of graft dysfunction led to the diagnosis of recurrent HAV infection. CONCLUSIONS: We suggest that the risk of HAV reinfection after liver transplantation may be far higher than expected as results may be misinterpreted as rejection episodes.

Hepatitis A↗

PubMed2004

Autocrine stimulation of rhadinovirus-transformed T cells by the chemokine CCL1/I-309.

The rhadinovirus herpesvirus saimiri transforms human T lymphocytes to stable growth in culture. Besides the viral oncogenes stpC and tip, little is understood about the transformation process at the cellular level. To identify cellular factors that might contribute to growth transformation, we compared cellular gene expression in pairs of herpesvirus saimiri-transformed and nontransformed human T-cell clones. Using cDNA arrays and suppressive subtractive hybridization, we were able to identify the chemokine CCL1/I-309 as one of the few cellular genes that are strongly overexpressed in T cells after growth transformation with herpesvirus saimiri. The transformed T cells expressed CCR8, the receptor for CCL1, which rapidly induced intracellular calcium ion levels. Neutralizing antibodies to CCL1 led to reduced secretion of interferon-gamma and tumor necrosis factor-alpha as well as to reduced proliferation rates in transformed T cells. Thus, we propose that growth transformation of human T cells with herpesvirus saimiri gives rise to an autocrine loop where the proliferation of transformed T cells is supported by the endogenous production of the chemokine CCL1.

Animals↗

PubMed2004

The T-cell lymphokine interleukin-26 targets epithelial cells through the interleukin-20 receptor 1 and interleukin-10 receptor 2 chains.

The cellular members of the interleukin-10 (IL-10) cytokine family share sequence homology with IL-10, whereas their sites of expression and their functions are divergent. One of these factors, AK155 or IL-26, was discovered because of its overexpression in human T lymphocytes after growth transformation by the simian rhadinovirus herpesvirus saimiri. In addition, the gene is transcribed in various types of primary and immortalized T-cells. Here we describe epithelial cells, namely colon carcinoma cells and keratinocytes, as targets of this T-cellular lymphokine. Purified recombinant IL-26 induced the rapid phosphorylation of the signal transducer and activator of transcription factors 1 and 3. As a result, secretion of IL-10 and IL-8, as well as cell surface expression of CD54 were enhanced. Moreover, we show that the IL-26 protein binds to heparin, is released from the cell surface, and can be functionally inhibited by heparin. The sensitivity to recombinant IL-26 of various cell lines strictly correlated with the expression of the long chain of the IL-20 receptor. Because blocking antibodies against either the short chain of the IL-10 receptor or the long chain of the IL-20 receptor inhibited IL-26-dependent signal transduction, and transient expression of these receptor chains induced IL-26 responsivity in non-sensitive cells, we propose that the IL-20 receptor 1 and IL-10 receptor 2 chains participate in forming the IL-26 receptor. Targeting epithelial cells, the T-cell lymphokine IL-26 is likely to play a role in local mechanisms of mucosal and cutaneous immunity.

Amino Acid Sequence↗

PubMed2004

Interleukin-26.

Interleukin-26 (IL-26), initially termed AK155, is a cellular sequence homolog to IL-10 belonging to the IL-10 cytokine family. Together with the related genes for interferon-gamma and IL-22/IL-TIF, il-26 maps to the human chromosomal region 12q15. The il-26 gene is one of the few differentially expressed genes specifying human T cells after growth-transformation with herpesvirus saimiri, a tumor virus of neo-tropical squirrel monkeys. Only herpesvirus saimiri-transformed T cells have been found to strongly over-express il-26 and to release the protein into the tissue culture supernatant. In a series of other T-cell lines and in native peripheral blood cells, il-26 is transcribed at low levels, but it is not detectable in B cells. Similarly to IL-10, the IL-26 protein forms homo-dimers. IL-26 is a candidate to contribute to the transformed phenotype of human T cells after infection by herpesvirus saimiri. Moreover, the T-lymphokine IL-26 is highly likely to play a role in normal and pathological hematology or immunology.

Amino Acid Sequence↗

PubMed2004

Global identification of three major genotypes of varicella-zoster virus: longitudinal clustering and strategies for genotyping.

By analysis of a single, variable, and short DNA sequence of 447 bp located within open reading frame 22 (ORF22), we discriminated three major varicella-zoster virus (VZV) genotypes. VZV isolates from all six inhabited continents that showed nearly complete homology to ORF22 of the European reference strain Dumas were assigned to the European (E) genotype. All Japanese isolates, defined as the Japanese (J) genotype, were identical in the respective genomic region and proved the most divergent from the E strains, carrying four distinct variations. The remaining isolates carried a combination of E- and J-specific variations in the target sequence and thus were collectively termed the mosaic (M) genotype. Three hundred twenty-six isolates collected in 27 countries were genotyped. A distinctive longitudinal distribution of VZV genotypes supports this approach. Among 111 isolates collected from European patients, 96.4% were genotype E. Consistent with this observation, approximately 80% of the VZV strains from the United States were also genotype E. Similarly, genotype E viruses were dominant in the Asian part of Russia and in eastern Australia. M genotype viruses were strongly dominant in tropical regions of Africa, Indochina, and Central America, and they were common in western Australia. However, genotype M viruses were also identified as a minority in several countries worldwide. Two major intertypic variations of genotype M strains were identified, suggesting that the M genotype can be further differentiated into subgenotypes. These data highlight the direction for future VZV genotyping efforts. This approach provides the first simple genotyping method for VZV strains in clinical samples.

Cluster Analysis↗

PubMed2003

The genome of herpesvirus saimiri C488 which is capable of transforming human T cells.

Herpesvirus saimiri (HVS), the rhadinovirus prototype, is apathogenic in the persistently infected natural host, the squirrel monkey, but causes acute T cell leukemia in other New World primate species. In contrast to subgroups A and B, only strains of HVS subgroup C such as C488 are capable of transforming primary human T cells to stable antigen-independent growth in culture. Here, we report the complete 155-kb genome sequence of the transformation-competent HVS strain C488. The A+T-rich unique L-DNA of 113,027 bp encodes at least 77 open reading frames and 5 URNAs. In addition to the viral oncogenes stp and tip, only a few genes including the transactivator orf50 and the glycoprotein orf51 are highly divergent. In a series of new primary HVS isolates, the subgroup-specific divergence of the orf50/orf51 alleles was studied. In these new isolates, the orf50/orf51 alleles of the respective subgroup segregate with the stp and/or tip oncogene alleles, which are essential for transformation.

Amino Acid Sequence↗

PubMed2003

Cloning of a new type II cytokine receptor activating signal transducer and activator of transcription (STAT)1, STAT2 and STAT3.

In the present paper, we report the identification of a new gene encoding a transmembrane protein of 520 amino acids, showing 22% amino acid identity with the extracellular domain of the interleukin (IL)-20 receptor. This gene, termed likely interleukin or cytokine receptor-2 ( LICR2 ), is located on chromosome 1, at 25 kb from the IL22R (IL-22 receptor) gene, and is constitutively expressed in most tissues. A chimaeric receptor, consisting of the extracellular domain of the IL-10 receptor alpha chain and the intracellular domain of LICR2, activated signal transducer and activator of transcription (STAT)1, STAT2, STAT3 and STAT5 upon IL-10 stimulation, in a Janus kinase 1-dependent manner. In contrast, none of the IL-10-related cytokines described so far could activate LICR2-transfected cells, suggesting that LICR2 is a signalling receptor for a new cytokine of the IL-10 family.

Cloning, Molecular↗

PubMed2003

Varicella-zoster virus isolates, but not the vaccine strain OKA, induce sensitivity to alpha-1 and beta-1 adrenergic stimulation of sensory neurones in culture.

The reactivation of varicella-zoster virus (VZV) from its persistent state in sensory neurones causes shingles and induces severe, long-lasting pain and hyperalgesia that often lead to postherpetic neuralgia. To investigate the VZV-induced neuropathic changes, we established conditions for the active infection of sensory neurones from rat dorsal root ganglia in vitro. After 2 days of culture, up to 50% of the cells expressed viral antigens of the immediate-early and late replication phase. The intracellular calcium ion concentration was monitored in individual cells by microfluorimetry. Whereas the calcium response to capsaicin was preserved, the VZV-infected neurones gained an unusual sensitivity to noradrenaline stimulation in contrast to non-infected cells. The adrenergic agonists phenylephrine and isoproterenol had a similar efficacy demonstrating that both alpha(1)- and beta(1)-adrenoreceptors were involved. The sensitivity to adrenergic stimulation was observed after infection with different wildtype isolates, but not with the attenuated vaccine strain OKA. The lack of noradrenaline sensitivity of vaccine-infected neurones demands a structural comparison of wildtype and vaccine viruses with and without phenotype. A partial sequence evaluation (26 kb) of the European OKA vaccine strain surprisingly revealed a series of nucleotide exchanges in comparison to presumably identical OKA strains from other sources, although VZV is generally considered genetically stable. In summary, we report that the infection with wildtype VZV isolates, but not with the vaccine strain, induces noradrenaline sensitivity in sensory neurones, which correlates with clinical and experimental observations of adrenergic effects involved in VZV-induced neuralgia.

Animals↗

PubMed2002

The interleukin-10 family of cytokines.

A family of interleukin-10 (IL-10)-related cytokines has emerged, comprising a series of herpesviral and poxviral members and several cellular sequence paralogs, including IL-19, IL-20, IL-22 [IL-10-related T-cell-derived inducible factor (IL-TIF)], IL-24 [melanoma differentiation-associated antigen 7 (MDA-7)] and IL-26 (AK155). Although the predicted helical structure of these homodimeric molecules is conserved, certain receptor-binding residues are variable and define the interaction with specific heterodimers of different type-2 cytokine receptors. This leads, through the activation of signal transducer and activator of transcription (STAT) factors, to diverse biological effects. For example, whereas IL-10 is a well-studied pleiotropic immunosuppressive and immunostimulatory cytokine, IL-22/IL-TIF mediates acute-phase response signals in hepatocytes and IL-20 induces the hyperproliferation of keratinocytes, which has been proposed as a pathogenic mechanism of psoriasis.

Amino Acid Sequence↗