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  • Springer (CrossRef)  (24)
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  • 1
    Language: English
    In: Medical Microbiology and Immunology, 2007, Vol.196(4), pp.181-190
    Description: Among emerging and re-emerging infectious diseases, influenza constitutes one of the major threats to mankind. In this review series epidemiologic, virologic and pathologic concerns raised by infections of humans with avian influenza virus A/H5N1 are discussed. This first part concentrates on epidemiologic concerns and virulence determinants. H5N1 spread over the world and caused a series of fowl pest outbreaks. Significant human-to-human transmissions have not been observed yet. Mutations that make the virus more compatible with human-to-human transmission may occur at any time. Nevertheless, no one can currently predict with certainty whether H5N1 will become a human pandemic virus.
    Keywords: Avian Influenza;
    ISSN: 0300-8584
    E-ISSN: 1432-1831
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  • 2
    Language: English
    In: Cellular and Molecular Life Sciences, 2011, Vol.68(6), pp.1079-1090
    Description: Human cytomegalovirus (HCMV) is a major pathogen in immunocompromised individuals. Here, non-toxic concentrations of the anti-cancer kinase inhibitor sorafenib were shown to inhibit replication of different HCMV strains (including a ganciclovir-resistant strain) in different cell types. In contrast to established anti-HCMV drugs, sorafenib inhibited HCMV major immediate early promoter activity and HCMV immediate early antigen (IEA) expression. Sorafenib is known to inhibit Raf. Comparison of sorafenib with the MEK inhibitor U0126 suggested that sorafenib inhibits HCMV IEA expression through inhibition of Raf but independently of signaling through the Raf downstream kinase MEK 1/2. In concordance, siRNA-mediated depletion of Raf but not of MEK-reduced IEA expression. In conclusion, sorafenib diminished HCMV replication in clinically relevant concentrations and inhibited HCMV IEA expression, a pathophysiologically relevant event that is not affected by established anti-HCMV drugs. Moreover, we demonstrated for the first time that Raf activation is involved in HCMV IEA expression.
    Keywords: Human cytomegalovirus ; Sorafenib ; Kinase inhibitor ; Raf ; Immediate early antigen ; Cancer chemotherapy ; Oncomodulation ; Antiviral therapy
    ISSN: 1420-682X
    E-ISSN: 1420-9071
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  • 3
    Language: English
    In: Medical Microbiology and Immunology, 2011, Vol.200(3), pp.193-202
    Description: The treatment of varicella-zoster virus (VZV) reactivation is based on nucleoside analogues acyclovir (ACV) and bromevinyldeoxyuridine (BVdU) and a phosphonic acid derivative (PFA). Drug-resistant mutants of 3 wild-type (WT) VZV strains were obtained by exposure of human retinal pigment epithelial (hRPE) cells inoculated with cell-free WT virus at increasing concentrations of ACV, BVdU, and PFA. In addition to single-drug resistance, a cross-resistance of isolates vs. ACV was observed for PFA-resistant strains. Single-nucleotide (nt) exchanges resulting in amino acid (aa) substitutions were observed within the DNA polymerase (ORF 28) and/or thymidine kinase (ORF 36) of 3 of 3 ACV-, 2 of 3 BVdU-, and 3 of 3 PFA-resistant strains. Interestingly, aa substitutions were also observed within the immediate-early regulatory protein and major transactivator IE 62 (ORF 62), and the envelope glycoprotein (g) I (ORF 67) of the BVdU-resistant mutant of strain PP. No aa substitutions were observed in the protein sequences of gene products encoded by ORF 5 (gK, a glycoprotein arranging exocytosis of viral-loaded vacuoles), ORF 14 (gC), ORF 31 (gB), ORF 37 (gH), ORF 47 (protein kinase, involved in major phosphorylating processes), ORF 60 (gL, important for syncytia forming of infected cells in combination with gH), ORF 63 (major transactivator, part of the tegument), and ORF 68 (gE, triggers fusion of viral loaded vacuoles with cell membranes by heterodimerizing with gI). Phenotypic analysis revealed a slow-growth phenotype and a formation of smaller plaques of resistant mutants. Future studies should prove the presence of those resistant mutants in herpes zoster patients and the potential consequences of their putative reduced fitness on the success of therapeutical interventions.
    Keywords: VZV ; Acyclovir ; Bromevinyldeoxyuridine ; Phosphonoformiat ; Brivudine ; IE62 ; Glycoprotein ; Resistance
    ISSN: 0300-8584
    E-ISSN: 1432-1831
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  • 4
    Language: English
    In: Medical Microbiology and Immunology, 2011, Vol.200(1), pp.53-60
    Description: Influenza A virus infection of macrophages and virus-induced pro-inflammatory gene expression are regarded to contribute to severity of influenza A virus-caused diseases. Although some data are available on cytokine production by influenza A virus-infected macrophages, systematic comparisons of the virus types are currently considered to be of high relevance in humans (pandemic H1N1/2009, seasonal H1N1, seasonal H3N2, highly pathogenic avian influenza H5N1) on pro-inflammatory potential, and relevant underlying cellular signalling events are missing. Here, we show that the infection of human monocyte-derived macrophages with pandemic H1N1/2009 (A/HH/01/2009), seasonal H1N1/1999 (A/New Caledonia/20/99), seasonal H3N2/2004 (A/California/7/2004) or highly pathogenic H5N1/2004 (A/Thailand/1(Kan-1)/04) results in similar infection rates. However, the investigated H1N1 strains caused delayed and decreased apoptosis in comparison with H3N2/2004 or H5N1/2004. Moreover, human macrophage infection with H3N2/2004 or H5N1/2004 but not with H1N1 viruses was associated with pronounced pro-inflammatory cytokine production and activation of relevant mitogen-activated protein kinase pathways as indicated by phosphorylation of p38, JNK and ERK 1/2. These findings are in line with clinical observations indicating enhanced disease severity in H3N2- or H5N1-infected patients compared to individuals infected with pandemic H1N1/2009 or seasonal H1N1.
    Keywords: Influenza A ; MAPK ; Cytokines ; Seasonal influenza ; H5N1 ; Pandemic H1N1/2009
    ISSN: 0300-8584
    E-ISSN: 1432-1831
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  • 5
    Language: English
    In: Medical Microbiology and Immunology, 2011, Vol.200(1), pp.1-5
    Description: The question whether human cytomegalovirus may affect cancer diseases has been discussed (very controversially) for decades. There are convinced believers and strict opponents of the idea that HCMV might be able to play a role in the course of cancer diseases. In parallel, the number of published reports on the topic is growing. Recently published and presented (Ranganathan P, Clark P, Kuo JS, Salamat S, Kalejta RF. A Survey of Human Cytomegalovirus Genomic Loci Present in Glioblastoma Multiforme Tissue Samples. 35th Annual International Herpes Workshop, Salt Lake City, 2010) data on HCMV detection in glioblastoma tissues and colocalisation of HCMV proteins with cellular proteins known to be relevant for glioblastoma progression motivated us to recapitulate the current state of evidence.
    Keywords: Cytomegalovirus ; Cancer ; Oncomodulation ; Tumour virus ; Glioblastoma ; Neuroblastoma
    ISSN: 0300-8584
    E-ISSN: 1432-1831
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  • 6
    Language: English
    In: Medical Microbiology and Immunology, 2012, Vol.201(3), pp.403-405
    Description: Erratum to: Med Microbiol Immunol (2011) 200:193–202 DOI 10.1007/s00430-011-0191-4 The authors would like to correct the errors in the original publication of the article. The errors include details under the sub-headings “Sequence evolution of selected VZV genes in resistant Mutants”, Discussion, and in Figs. 3 and 4 and Table 3. The corrected sentences, figures and table are given below for your reading. Fig. 3 Amino acid substitutions found within the vDNA pol encoded by ORF28. Black boxes indicate highly conserved regions. Mutations found in our resistant isolates are indicated in red
    Keywords: Public Health;
    ISSN: 0300-8584
    E-ISSN: 1432-1831
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  • 7
    Language: English
    In: Medical Microbiology and Immunology, 2013, Vol.202(1), pp.37-47
    Description: Although several host factors have been identified to influence the course of HCMV infection, it still remains unclear why in AIDS patients without highly active antiretroviral therapy human cytomegalovirus (HCMV) retinitis is one of the most common opportunistic infections, whereas in other immunosuppressed individuals it has a low incidence. It was suggested that HCMV glycoprotein B strains may be suitable as marker for virulence and HCMV retinitis. Moreover, UL144 ORF, a member of the TNF-α receptor superfamily, may play a crucial role in innate defences and adaptive immune response of HCMV infection. Furthermore, sequence analyses of HCMV genes UL128, UL130, and UL131A as major determinants of virus entry and replication in epithelial and other cell types were performed. To evaluate the association of sequence variability of depicted viral genes with HCMV retinitis and in vitro growth properties in retinal pigment epithelial cells (RPE) and human foreskin fibroblasts (HFF), we compared 14 HCMV isolates obtained from vitreous fluid and urine of AIDS patients with clinically proven HCMV retinitis. Isolates were analyzed by PCR cycle sequencing and phylogenetic analysis. In addition, sequences of HCMV strains AF1, U8, U11, VR1814, and its cell culture adapted derivates were included. Sequence analysis of gB yielded three genetic subtypes (gB type 1 (5 isolates), gB type 2 (12 isolates), and gB type 3 (5 Isolates)), whereas sequence analysis of UL144 showed a greater diversity (7 isolates type 1A, 2 isolates type 1C, 7 isolates type 2, and 3 isolates type 3). In contrast, the UL128, UL130, and UL131A genes of all low-passage isolates were highly conserved and showed no preferential clustering. Moreover, in HFF and RPE cells, all of our HCMV isolates replicated efficiently independently of their genetic subtype. In conclusion, beside a possible link between the gB subtype 2 and HCMV retinitis, our study found no direct evidence for a connection between UL144/UL128/UL130/UL131A genotypes and the incidence of HCMV retinitis in AIDS patients.
    Keywords: Cytomegalovirus ; Viral tropism and virulence ; Retinitis ; AIDS
    ISSN: 0300-8584
    E-ISSN: 1432-1831
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  • 8
    Language: English
    In: Medical Microbiology and Immunology, 2007, Vol.196(4), pp.191-201
    Description: Among emerging and re-emerging infectious diseases, influenza constitutes one of the major threats to mankind. In this review series epidemiologic, virologic and pathologic concerns raised by infections of humans with avian influenza virus A/H5N1 are discussed. The second part focuses on experimental and clinical results, which give insights in the pathogenic mechanisms of H5N1 infection in humans. H5N1 is poorly transmitted to humans. However, H5N1-induced disease is very severe. More information on the role entry barriers, H5N1 target cells and on H5N1-induced modulation of the host immune response is needed to learn more about the determinants of H5N1 pathogenicity.
    Keywords: Avian Influenza;
    ISSN: 0300-8584
    E-ISSN: 1432-1831
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  • 9
    Language: English
    In: Medical Microbiology and Immunology, 2007, Vol.196(4), pp.203-212
    Description: Among emerging and re-emerging infectious diseases, influenza constitutes one of the major threats to mankind. In this review series epidemiologic, virologic and pathologic concerns raised by infections of humans with avian influenza virus A/H5N1 as well as treatment options are discussed. The third part discusses therapeutic options. Neuraminidase (NA) inhibitors are the most promising agents despite uncertainty about efficacy. Dosage increase, prolonged treatment or combination therapies may increase treatment efficacy and/or inhibit resistance formation. Immune system dysregulation contributes to H5N1 disease. Although current evidence does not support the use of anti-inflammatory drugs beneficial effects cannot be excluded at later disease stages.
    Keywords: Antiviral Agents ; Avian Influenza;
    ISSN: 0300-8584
    E-ISSN: 1432-1831
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  • 10
    Language: English
    In: Medical Microbiology and Immunology, 2010, Vol.199(4), pp.291-297
    Description: Hypercytokinaemia is thought to contribute to highly pathogenic H5N1 influenza A virus disease. Glycyrrhizin is known to exert immunomodulatory and anti-inflammatory effects and therefore a candidate drug for the control of H5N1-induced pro-inflammatory gene expression. Here, the effects of an approved parenteral glycyrrhizin preparation were investigated on H5N1 virus replication, H5N1-induced pro-inflammatory responses, and H5N1-induced apoptosis in human monocyte-derived macrophages. Glycyrrhizin 100 μg/ml, a therapeutically achievable concentration, impaired H5N1-induced production of CXCL10, interleukin 6, and CCL5 and inhibited H5N1-induced apoptosis but did not interfere with H5N1 replication. Global inhibition of immune responses may result in the loss of control of virus replication by cytotoxic immune cells including natural killer cells and cytotoxic CD8 + T-lymphocytes. Notably, glycyrrhizin concentrations that inhibited H5N1-induced pro-inflammatory gene expression did not affect cytolytic activity of natural killer cells. Since H5N1-induced hypercytokinaemia is considered to play an important role within H5N1 pathogenesis, glycyrrhizin may complement the arsenal of potential drugs for the treatment of H5N1 disease.
    Keywords: Glycyrrhizin ; H5N1 ; Cytokines ; Monocyte-derived macrophages
    ISSN: 0300-8584
    E-ISSN: 1432-1831
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