TY - JOUR A1 - Aguzzi, A. A1 - Wagner, E. F. A1 - Netzer, K. O. A1 - Bothe, K. A1 - Anhauser, I. A1 - Rethwilm, Axel T1 - Human foamy virus proteins accumulate in neurons and induce multinucleated giant cells in the brain of transgenic mice N2 - Humanfoamy virus (HFV) is a retrovirus encoding structural genes and, like human immunodeficiency virus and human T ceU leukemia virus I, several anciUary reading frames collectively termed the belgenes. We have previously shown that HFV transgenic mice develop an encephalopathy with neuronal loss in hippocampus and cerebral cortex. We have now raised and characterized rabbit antisera to various recombinant portions of gag, pot, env, and bel-I, the viraltransactivator. Immunoreactivity for gag and bel-I was observed in nuclei and processes of hippocampal and cortical neurons before the onset of morphological lesions and correlated with the appearance of HFV mRNA. Astrocyte-derived multinucleated giant ceUs containing HFV proteins were present in the brain oftransgenic mice coexpressingfuU- length HFV genes but not in mice expressing truncated gag and env, suggesting that these genes contain afusogenic domain. Expression of fuU-length structural genes decreased the life expectancy oftransgenic mice, implying an a4Juvant rolefor these proteins in HFV-induced brain damage. (Am] Pathol 1993, 142:1061-1072) KW - Molekularpathologie Y1 - 1993 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-47356 ER - TY - JOUR A1 - Hong, Liu A1 - Bräutigam, Sandra A1 - Rethwilm, Axel T1 - Expression of the human foamy virus bel-1 transactivator in insect cells N2 - The human foamy virus (HFV) bel-l transactivator protein was expressed in insect cells by a recombinant baculovirus. For the generation of the recombinant baculovirus, Acbel-1, the bel-l gene of an HFV mutant was used, that bears truncations in the bel-l overlapping bel-2 open reading frame. Acbel-1 infected Sf9 cells produced high amounts of recombinant protein of the same electrophoretic mobility (36 kD) as bel-l expressed in mammalian cells. The baculovirus expressed bel-l proteinwas readily identified by a polyclonal rabbit serum directed against bel-1 in immunoblot assay. As in mammalian cells, bel-l was predominantly localized to the nucleus of Acbel-1 infected insect cells. The baculovirus expressed bel-1 proteinwill be of use to determine the action of this novel viral transactivator more precisely. KW - Virologie KW - Human foamy virus bel-l transactivator; Expression in insect cells Y1 - 1993 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61383 ER - TY - JOUR A1 - Baunach, Gerald A1 - Maurer, Bernd A1 - Hahn, Heidi A1 - Kranz, Manuela A1 - Rethwilm, Axel T1 - Functional analysis of human foamy virus accessory reading frames N2 - No abstract available KW - Virologie Y1 - 1993 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61398 ER - TY - JOUR A1 - Erlwein, Otto A1 - Rethwilm, Axel T1 - BEL-1 transactivator responsive sequences in the long terminal repeat of human foamy virus N2 - No abstract available KW - Virologie Y1 - 1993 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61402 ER - 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 -