@article{RethwilmDaraiRoesenetal.1987, author = {Rethwilm, Axel and Darai, G. and R{\"o}sen, A. and Maurer, Bernd and Fl{\"u}gel, Rolf M.}, title = {Molecular cloning of the genome of human spumaretrovirus}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61518}, year = {1987}, abstract = {DNA ofhuman spumaretrovirus (HSRV) was cloned from both cDNA and from viral DNA into phage A and bacterial plasmid vectors. The recombinant plasm.ids harboring viral DNA were characterized by Southern blot hybridization and restriction mapping. Physical maps were constructed from cDNA and found to be colinear with the restriction maps obtained from viral DNA. The recombinant clones isolated contained viral DNA inserts which rangein size from 2.2 kb to 15.4 kb. The recombinant clones allowed to construct a physical map of the complete HSRV provirus of 12.2 kb.}, subject = {Virologie}, language = {en} } @article{KincaidChenCoxetal.2014, author = {Kincaid, Rodney P. and Chen, Yating and Cox, Jennifer E. and Rethwilm, Axel and Sullivan, Christopher S.}, title = {Noncanonical MicroRNA (miRNA) Biogenesis Gives Rise to Retroviral Mimics of Lymphoproliferative and Immunosuppressive Host miRNAs}, series = {mBio}, volume = {5}, journal = {mBio}, number = {2}, issn = {2150-7511}, doi = {10.1128/mBio.00074-14}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-117216}, pages = {e00074-14}, year = {2014}, abstract = {MicroRNAs (miRNAs) play regulatory roles in diverse processes in both eukaryotic hosts and their viruses, yet fundamental questions remain about which viruses code for miRNAs and the functions that they serve. Simian foamy viruses (SFVs) of Old World monkeys and apes can zoonotically infect humans and, by ill-defined mechanisms, take up lifelong infections in their hosts. Here, we report that SFVs encode multiple miRNAs via a noncanonical mode of biogenesis. The primary SFV miRNA transcripts (pri-miRNAs) are transcribed by RNA polymerase III (RNAP III) and take multiple forms, including some that are cleaved by Drosha. However, these miRNAs are generated in a context-dependent fashion, as longer RNAP II transcripts spanning this region are resistant to Drosha cleavage. This suggests that the virus may avoid any fitness penalty that could be associated with viral genome/transcript cleavage. Two SFV miRNAs share sequence similarity and functionality with notable host miRNAs, the lymphoproliferative miRNA miR-155 and the innate immunity suppressor miR-132. These results have important implications regarding foamy virus biology, viral miRNAs, and the development of retroviral-based vectors. IMPORTANCE Fundamental questions remain about which viruses encode miRNAs and their associated functions. Currently, few natural viruses with RNA genomes have been reported to encode miRNAs. Simian foamy viruses are retroviruses that are prevalent in nonhuman host populations, and some can zoonotically infect humans who hunt primates or work as animal caretakers. We identify a cluster of miRNAs encoded by SFV. Characterization of these miRNAs reveals evolutionarily conserved, unconventional mechanisms to generate small RNAs. Several SFV miRNAs share sequence similarity and functionality with host miRNAs, including the oncogenic miRNA miR-155 and innate immunity suppressor miR-132. Strikingly, unrelated herpesviruses also tap into one or both of these same regulatory pathways, implying relevance to a broad range of viruses. These findings provide new insights with respect to foamy virus biology and vectorology.}, language = {en} } @article{SchliephakeRethwilm1994, author = {Schliephake, Andreas W. and Rethwilm, Axel}, title = {Nuclear Localization of Foamy Virus Gag Precursor Protein}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61371}, year = {1994}, abstract = {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.}, subject = {Virologie}, language = {en} } @article{FluegelMaurerBannertetal.1987, author = {Fl{\"u}gel, Rolf M. and Maurer, Bernd and Bannert, Helmut and Rethwilm, Axel and Schnitzler, Paul and Darai, Gholamreza}, title = {Nucleotide sequence analysis of a cloned DNA fragment from human cells reveals homology to retrotransposons}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61525}, year = {1987}, abstract = {During molecular cloning of proviral DNA of human. spumaretroVirus, various recombinant clones were estabUshed and analyzed. Blot hybridization revealed that one of the recoinbinant plasmids bad the characteristic features of a member of the long interspersed repetitive sequences famlly. The DNA element was analyzed by restrictioil mapping and nuelootide sequencing. It showed a high degree of amino acid sequence homology of 54.3\% when conipared with the 5'-terminal part of the pol gelie product of the murine retrotransposon LIMd. The 3' region of the cloned DNA element encodes proteins witb an even higher degree of homology of 67.4\% in comparison to the corresponding parts of a member of the primate Kpnl sequence family.}, subject = {Virologie}, language = {en} } @article{FluegelRethwilmMaureretal.1987, author = {Fl{\"u}gel, Rolf M. and Rethwilm, Axel and Maurer, Bernd and Darai, Gholamreza}, title = {Nucleotide sequence analysis of the env gene and its flanking regions of the human spumaretrovirus reveals two novel genes}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61509}, year = {1987}, abstract = {Recombinant clonesthat represent the 3' part ofthe genome of the human spumaretrovirus (foamy virus) were established from viral DNA and from DNA complementary to viral RNA. The recombinant clones were characterized by blot hybridizations and nucleotide sequence analysis. The deduced protein sequence of the clones at their 5' ends was found to be homologous to the 3' domain of retroviral reverse transcriptases. Downstream of a small intergerne pol-env region a long open reading frame of 985 amino acid residues was identified that according to its genomic location, size, glycosylation signals, and hydrophobicity protile closely resembles the lentiviral env genes. The spumaretroviral env gene is followed by two open reading frames, termed bel-l and bel-2 which are located between env and the long terminal repeat region. The long terminal repeat of 1259 nucleotides is preceded by a polypurine tract and contains the canonical signal sequences characteristic for transcriptional regulation of retroviruses. The provisional classitication of the spumaretrovirus subfamily is discussed.}, subject = {Virologie}, language = {en} } @article{BotheAguzziLassmannetal.1991, author = {Bothe, Katrin and Aguzzi, Adriano and Lassmann, Hans and Rethwilm, Axel and Horak, Ivan}, title = {Progressive encephalopathy and myopathy in transgenic mice expressing human foamy virus genes}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61453}, year = {1991}, abstract = {Transgenie mice carrying the bel region of human foamy retrovirus (HFV) under transcriptional control of its own long terminal repeat expressed tbe transgene in their centrat nervous systems and in smootb and striated muscle tissues. The animals developed a progressive degenerative disease of tbe centrat nervous system and of the striated muscle. Because expression of tbe transgene was dosely correlated witb the appearance of structural damage and inflammatory reactions were scanty, the disease is likely to be caused directly by tbe HFV proteins. These unexpected findings call for a reevaluation of tbe patbogenic potential of HFV in humans.}, subject = {Virologie}, language = {en} } @article{HahnBaunachBraeutigametal.1994, author = {Hahn, Heidi and Baunach, Gerald and Br{\"a}utigam, Sandra and Mergia, Ayalew and Neumann-Haefelin, Dieter and Daniel, Muthiah D. and McClure, Myra O. and Rethwilm, Axel}, title = {Reactivity of primate sera to foamy virus Gag and Bet proteins}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61366}, year = {1994}, abstract = {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.}, subject = {Virologie}, language = {en} } @article{HartlBodemJochheimetal.2011, author = {Hartl, Maximilian J. and Bodem, Jochen and Jochheim, Fabian and Rethwilm, Axel and R{\"o}sch, Paul and W{\"o}hrl, Birgitta M.}, title = {Regulation of foamy virus protease activity by viral RNA}, series = {Retrovirology}, volume = {8}, journal = {Retrovirology}, number = {Suppl. 1}, doi = {10.1186/1742-4690-8-S1-A228}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-142248}, pages = {A228}, year = {2011}, abstract = {No abstract available.}, language = {en} } @inproceedings{MoriRethwilmSchwinnetal.1990, author = {Mori, Kazuyasu and Rethwilm, Axel and Schwinn, Andreas and Horak, Ivan}, title = {Replication of human immunodeficiency virus type 1 in human t-cells expressing antisense RNA}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-86426}, year = {1990}, abstract = {No abstract available.}, subject = {HIV}, language = {en} } @article{JocherRethwilmKapposetal.1990, author = {Jocher, R. and Rethwilm, Axel and Kappos, L. and ter Meulen, Volker}, title = {Search for retroviral sequences in peripheral blood mononuclear cells and brain tissue of multiple sclerosis patients}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61462}, year = {1990}, abstract = {DNAs from peripheral blood mononuclear cells (PBMCs) of 21 patients with multiple sclerosis (MS), 1 patient with tropical spastic paraparesis (TSP) as well as DNAs from brain and spinal cord of 5 MS cases and 3 controls were examined for human T-cell lymphotropic virus (HTLV)-related sequences by polymerase chain reaction. The primers used were derived from the HTLV-1 gag, env and tax genes. Amplified products were separated on agarase gels, blotted onto nylon membranes and hybridized to specific radiolabelled oligonucleotides. The sensitivity of amplification and hybridization was one copy of target DNA in 10\8^5\) cellular genomes. None of the specimens was positive for HTLV-1 sequences except the TSP probe. These negative data are all the more significant because brain -material from MS patients was used in these studies. Our studies thus fail to support speculations that HTLV-I is involved in the aetiology of multiple sclerosis.}, subject = {Virologie}, language = {en} }