TY  - JOUR
A1  - Brinkmann, R.
A1  - Schwinn, A.
A1  - Müller, J.
A1  - Stahl-Hennig, C.
A1  - Coulibaly, C.
A1  - Hunsmann, G.
A1  - Czub, S.
A1  - Rethwilm, Axel
A1  - Dörries, R.
A1  - ter Meulen, Volker
T1  - In vitro and in vivo infection of rhesus monkey microglial cells by simian immunodeficiency virus
N2  - The observation that microglial cells in brain tissue are probably a major target for human immunodeficiency virus (HIV) infection has raised interest in the pathogenic role of this cell population for the development of neuro-AIOS. Since it is very difficult to obtain microglia from normal or diseased human brain we studied microglial cells isolated from fresh brain tissue of uninfected and simian immunodeficiency virus (SIV) infected rhesus monkeys (Macacca mulatta) in comparison to peripheral blood macrophages. Besides the characterization of the phenotypes of these two cell populations, we examined the replication of SIV in the cells in addition to the effect of viral infection on the expression of cell surface molecules. We found that microglia and macrophages support replication of the wild-type SIV\(_{mac25}\), strain as well as the infectious clone (SIV\(_239\)). Infectious viruswas produced and a CPE developed. Isolated microglial cells from SIV-infected monkeys were latently infected independent of the presence of neuropathological lesions and produced infectious virus after 20-25 days in culture. In situ hybridization revealed that only a small percentage of isolated microglial cells are productively infected in vivo, yet the majority of these expressed MHC class II molecules. This indicated a state of activation that is acquired in vivo. These findings indicate that microglia are a prime target cell for SIV infection in CNS tissue.
KW  - Virologie
Y1  - 1993
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61415
ER  - 
TY  - JOUR
A1  - Netzer, Kai O.
A1  - Schliephake, Andreas
A1  - Maurer, Bernd
A1  - Watanabe, Rihito
A1  - Aguzzi, Adriano
A1  - Rethwilm, Axel
T1  - Identification of pol-related gene products of human foamy virus
N2  - Human foamy viruspol gene fragments were molecularly cloned into a procaryotic expression vector. The expression pattern of the cloned fragments and nucleotide sequence analysis of the 5' pol gene region revealed that in HFV the protease (PR) is located in the pol open reading frame. Purified recombinant proteins were used to generate antibodies in rats. ln immunoblot assay, using infected cells as antigen, a precursor protein with an apparent molecular mass (M,) of 127K was identified by antibodies directed against the reverse transcriptase (RT), RNaseH, or integrase (IN) domeins of pol. With concentrated virus as antigen, the RT and RNaseH antibodies recognized a protein of 80K, the IN antiserum recognized a protein of 40K, and the PR antiserum detected a protein of approximately 10K.
KW  - Virologie
Y1  - 1993
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61429
ER  - 
TY  - JOUR
A1  - Müller, J. G.
A1  - Krenn, V.
A1  - Schindler, C.
A1  - Czub, S.
A1  - Stahl-Henning, C.
A1  - Coulibaly, C.
A1  - Hunsmann, G.
A1  - Kneitz, C.
A1  - Kerkau, Thomas
A1  - Rethwilm, Axel
A1  - terMeulen, Volker
T1  - Alterations of thymus cortical epithelium and interdigitating dendritic cells but no increase of thymocyte cell death in the early course of simian immunodeficiency virus infection
N2  - No abstract available
Y1  - 1993
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-32583
ER  - 
TY  - JOUR
A1  - Müller, J.
A1  - Krenn, V.
A1  - Czub, S.
A1  - Schindler, C.
A1  - Kneitz, C.
A1  - Kerkau, T.
A1  - Stahl-Henning, C.
A1  - Coulibaly, C.
A1  - Hunsmann, G.
A1  - Rethwilm, Axel
A1  - ter Meulen, Volker
A1  - Müller-Hermelink, H. K.
T1  - The thymus in SIV infection
N2  - no abstract available
KW  - HIV-Infektion
KW  - Tierversuch
KW  - Tiermodell
KW  - Retroviren-Infektion
KW  - Kongress
KW  - Hamburg
Y1  - 1993
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-80265
ER  - 
TY  - JOUR
A1  - Siwka, Wieslaw
A1  - Schwinn, Andreas
A1  - Baczko, Knut
A1  - Pardowitz, Iancu
A1  - Mhalu, Fred
A1  - Shao, John
A1  - Rethwilm, Axel
A1  - ter Meulen, Volker
T1  - vpu and env sequence variability of HIV-1 isolates from Tanzania
N2  - No abstract available
KW  - Virologie
Y1  - 1994
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61355
ER  - 
TY  - JOUR
A1  - Hahn, Heidi
A1  - Baunach, Gerald
A1  - Bräutigam, Sandra
A1  - Mergia, Ayalew
A1  - Neumann-Haefelin, Dieter
A1  - Daniel, Muthiah D.
A1  - McClure, Myra O.
A1  - Rethwilm, Axel
T1  - Reactivity of primate sera to foamy virus Gag and Bet proteins
N2  - In order to establish criteria for the Serodiagnosis of foamy virus infections we investigated the extent to which sera from iofected individuals of human and primate origin react with structural and non-structural virus proteins in immunoblot assays. Using lysates from infected cells as the source of virus antigen, antibodies were preferentially detected against the Gag proteins and the non-structural Bet protein. Both the Gag precursor molecules of 70 and 74K apparent M\(_r\) and the cytoplasmic 60K M\(_r\) Bet protein were found to be phosphorylated, the latter being synthesized in large amounts in infected cells. Rahbit antiserum raised against recombinant human foamy virus (HFV) Gag major capsid protein cross-reacted with foamy viruses of chimpanzee, gorilla, orang-utan, rhesus monkey and Mrican green monkey origin. This was reßected by a broad cross-reactivity of the respective monkey sera to the Gag proteins of the various foamy virus isolates. Cross-reactivity of antisera against the Bet protein was restricted to viruses from man and the great apes. Recombinant Gag and Bet proteins expressed in prokaryotes or in insect cells were readily recognized by foamy virus-positive primate sera. Screening serum samples from chimpanzees with HFV Gag and Bet proteins expressed by recombinant baculoviruses revealed that 18 out of 35 (52%) were positive for Gag antibodies. Of these, 13 (72 o/o) showed antiborlies against the Bet protein, indicating that Bet antigen is of value in sero1ogical screening for foamy virus infections.
KW  - Virologie
Y1  - 1994
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61366
ER  - 
TY  - JOUR
A1  - Schliephake, Andreas W.
A1  - Rethwilm, Axel
T1  - Nuclear Localization of Foamy Virus Gag Precursor Protein
N2  - All foamy viruses give rise to a strong nuclear staining when infected cells are reacted with sera from infected hosts. This nuclear ftuorescence distinguishes foamy viruses from all other retroviruses. The experiments reported here indicate that the foamy virus Gag precursor protein is transiently located in the nuclei of infected cells and this is the likely reason for the typical foamy virus nuclear fluorescence. By using the vaccinia virus expression system, a conserved basic sequence motif in the nucleocapsid domain of foamy virus Cag proteins was identified to be responsible for the nuclear transport of the gag precursor molecule. Tbis motif was also found to be able to direct a heterologous protein, the Gag protein of human immunodeficiency virus, into the nucleus.
KW  - Virologie
Y1  - 1994
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61371
ER  - 
TY  - JOUR
A1  - Hartl, Maximilian J.
A1  - Bodem, Jochen
A1  - Jochheim, Fabian
A1  - Rethwilm, Axel
A1  - Rösch, Paul
A1  - Wöhrl, Birgitta M.
T1  - Regulation of foamy virus protease activity by viral RNA
JF  - Retrovirology
N2  - No abstract available.
KW  - Virologie
Y1  - 2011
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-142248
VL  - 8
IS  - Suppl. 1
ER  - 
TY  - JOUR
A1  - Kasang, Christa
A1  - Kalluvya, Samuel
A1  - Majinge, Charles
A1  - Stich, August
A1  - Bodem, Jochen
A1  - Kongola, Gilbert
A1  - Jacobs, Graeme B.
A1  - Mllewa, Mathias
A1  - Mildner, Miriam
A1  - Hensel, Irina
A1  - Horn, Anne
A1  - Preiser, Wolfgang
A1  - van Zyl, Gert
A1  - Klinker, Hartwig
A1  - Koutsilieri, Eleni
A1  - Rethwilm, Axel
A1  - Scheller, Carsten
A1  - Weissbrich, Benedikt
T1  - HIV drug resistance (HIVDR) in antiretroviral therapy-naive patients in Tanzania not eligible for WHO threshold HIVDR survey is dramatically high
N2  - Background: The World Health Organization (WHO) has recommended guidelines for a HIV drug resistance (HIVDR) survey for resource-limited countries. Eligibility criteria for patients include age below 25 years in order to focus on the prevalence of transmitted HIVDR (tHIVDR) in newly-infected individuals. Most of the participating sites across Africa have so far reported tHIVDR prevalences of below 5%. In this study we investigated whether the rate of HIVDR in patients ,25 years is representative for HIVDR in the rest of the therapy-naive population. Methods and Findings: HIVDR was determined in 88 sequentially enrolled ART-naive patients from Mwanza, Tanzania (mean age 35.4 years). Twenty patients were aged, 25 years and 68 patients were aged 25–63 years. The frequency of HIVDR in the study population was 14.8% (95%; CI 0.072–0.223) and independent of NVP-resistance induced by prevention of mother-to-child transmission programs. Patients .25 years had a significantly higher HIVDR frequency than younger patients (19.1%; 95% CI 0.095–0.28) versus 0%, P = 0.0344). In 2 out of the 16 patients with HIVDR we found traces of antiretrovirals (ARVs) in plasma. Conclusions: ART-naive patients aged over 25 years exhibited significantly higher HIVDR than younger patients. Detection of traces of ARVs in individuals with HIVDR suggests that besides transmission, undisclosed misuse of ARVs may constitute a significant factor in the generation of the observed high HIVDR rate. The current WHO tHIVDR survey that is solely focused on the transmission of HIVDR and that excludes patients over 25 years of age may therefore result in substantial underestimation of the prevalence of HIVDR in the therapy-naive population. Similar studies should be performed also in other areas to test whether the so far reported optimistic picture of low HIVDR prevalence in young individuals is really representative for the rest of the ART-naive HIV-infected population.
KW  - Tansania
KW  - HIV
Y1  - 2011
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-69024
ER  - 
TY  - JOUR
A1  - Lindemann, Dirk
A1  - Rethwilm, Axel
T1  - Foamy Virus Biology and Its Application for Vector Development
JF  - Viruses
N2  - Spuma- or foamy viruses (FV), endemic in most non-human primates, cats, cattle and horses, comprise a special type of retrovirus that has developed a replication strategy combining features of both retroviruses and hepadnaviruses. Unique features of FVs include an apparent apathogenicity in natural hosts as well as zoonotically infected humans, a reverse transcription of the packaged viral RNA genome late during viral replication resulting in an infectious DNA genome in released FV particles and a special particle release strategy depending capsid and glycoprotein coexpression and specific interaction between both components. In addition, particular features with respect to the integration profile into the host genomic DNA discriminate FV from orthoretroviruses. It appears that some inherent properties of FV vectors set them favorably apart from orthoretroviral vectors and ask for additional basic research on the viruses as well as on the application in Gene Therapy. This review will summarize the current knowledge of FV biology and the development as a gene transfer system.
KW  - terminal gag domain
KW  - env leader protein
KW  - enhance viral transcription
KW  - subviral particle release
KW  - cell-cycle dependence
KW  - foamyviruses
KW  - retroviral vectors
KW  - LAD
KW  - Fanconi Anemia
KW  - cis-acting sequences
KW  - dna-binding protein
KW  - pol messenger-rna
KW  - reverse-transcriptase
KW  - gene-expression
Y1  - 2011
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-139811
VL  - 3
IS  - 5
ER  -