TY - JOUR AB - Human norovirus is the leading cause of acute gastroenteritis worldwide, however despite the significance of this pathogen, we have a limited understanding of how noroviruses cause disease, and modulate the innate immune response. Programmed cell death (PCD) is an important part of the innate response to invading pathogens, but little is known about how specific PCD pathways contribute to norovirus replication. Here, we reveal that murine norovirus (MNV) virus-induced PCD in macrophages correlates with the release of infectious virus. We subsequently show, genetically and chemically, that MNV-induced cell death and viral replication occurs independent of the activity of inflammatory mediators. Further analysis revealed that MNV infection promotes the cleavage of apoptotic caspase-3 and PARP. Correspondingly, pan-caspase inhibition, or BAX and BAK deficiency, perturbed viral replication rates and delayed virus release and cell death. These results provide new insights into how MNV harnesses cell death to increase viral burden. AU - Deerain, J.M.* AU - Aktepe, T.E.* AU - Trenerry, A.M.* AU - Ebert, G. AU - Hyde, J.L.* AU - Charry, K.* AU - Edgington-Mitchell, L.* AU - Xu, B.* AU - Ambrose, R.L.* AU - Sarvestani, S.T.* AU - Lawlor, K.E.* AU - Pearson, J.S.* AU - White, P.A.* AU - Mackenzie, J.M.* C1 - 69121 C2 - 53856 CY - 525 B St, Ste 1900, San Diego, Ca 92101-4495 Usa TI - Murine norovirus infection of macrophages induces intrinsic apoptosis as the major form of programmed cell death. JO - Virology VL - 589 PB - Academic Press Inc Elsevier Science PY - 2024 SN - 0042-6822 ER - TY - JOUR AB - The early and mid-career researchers (EMCRs) of scientific communities represent the forefront of research and the future direction in which a field takes. The opinions of this key demographic are not commonly aggregated to audit fields and precisely demonstrate where challenges lie for the future. To address this, we initiated the inaugural International Emerging Researchers Workshop for the global Hepatitis B and Hepatitis D scientific community (75 individuals). The cohort was split into small discussion groups and the significant problems, challenges, and future directions were assessed. Here, we summarise the outcome of these discussions and outline the future directions suggested by the EMCR community. We show an effective approach to gauging and accumulating the ideas of EMCRs and provide a succinct summary of the significant gaps remaining in the Hepatitis B and Hepatitis D field. AU - Tu, T.* AU - Wettengel, J.M. AU - Xia, Y.* AU - Testoni, B.* AU - Littlejohn, M.* AU - Le Bert, N.* AU - Ebert, G. AU - Verrier, E.R.* AU - Tavis, J.E.* AU - Cohen, C.* C1 - 70524 C2 - 55581 TI - Major open questions in the hepatitis B and D field – Proceedings of the inaugural International emerging hepatitis B and hepatitis D researchers workshop. JO - Virology VL - 595 PY - 2024 SN - 0042-6822 ER - TY - JOUR AB - Risk factors for disease progression and severity of SARS-CoV-2 infections require an understanding of acute and long-term virological and immunological dynamics. Fifty-one RT-PCR positive COVID-19 outpatients were recruited between May and December 2020 in Munich, Germany, and followed up at multiple defined timepoints for up to one year. RT-PCR and viral culture were performed and seroresponses measured. Participants were classified applying the WHO clinical progression scale. Short symptom to test time (median 5.0 days; p = 0.0016) and high viral loads (VL; median maximum VL: 3∙108 copies/mL; p = 0.0015) were indicative for viral culture positivity. Participants with WHO grade 3 at baseline had significantly higher VLs compared to those with WHO 1 and 2 (p = 0.01). VLs dropped fast within 1 week of symptom onset. Maximum VLs were positively correlated with the magnitude of Ro-N-Ig seroresponse (p = 0.022). Our results describe the dynamics of VLs and antibodies to SARS-CoV-2 in mild to moderate cases that can support public health measures during the ongoing global pandemic. AU - Puchinger, K.* AU - Castelletti, N. AU - Rubio-Acero, R.* AU - Geldmacher, C.* AU - Eser, T.M.* AU - Deák, F.* AU - Paunovic, I.* AU - Bakuli, A.* AU - Saathoff, E.* AU - von Meyer, A.* AU - Markgraf, A.* AU - Falk, P.* AU - Reich, J.* AU - Riess, F.* AU - Girl, P.* AU - Müller, K.* AU - Radon, K.* AU - Guggenbüehl Noller, J.M.* AU - Wölfel, R.* AU - Hoelscher, M.* AU - Kroidl, I.* AU - Wieser, A.* AU - Olbrich, L.* AU - KORA Study Group (Fuchs, C. AU - Theis, F.J. AU - Hasenauer, J.) C1 - 64498 C2 - 52228 SP - 37-43 TI - The interplay of viral loads, clinical presentation, and serological responses in SARS-CoV-2 – Results from a prospective cohort of outpatient COVID-19 cases. JO - Virology VL - 569 PY - 2022 SN - 0042-6822 ER - TY - JOUR AB - HIV-1 NL4-3 Vpu induces downregulation of cell surface CD155, a ligand for the DNAM-1 activating receptor of NK and CD8(+) T cells, to evade NK cell mediated immune response. Here we show that the conserved alanine residues at positions 10, 14 and 18 in the TM domain of Vpu are required for the efficient downregulation of cell surface CD155. In contrast, the CK-2 phosphorylation sites and the second α-helix in the cytoplasmic Vpu domain have no influence on the surface expression of CD155. Thus, compared to Vpu׳s effect on CD4, NTB-A and tetherin, the Vpu mediated downregulation of CD155 is an independent Vpu function. We finally show that in contrast to other lentiviral strains, only Vpu and Nef from HIV-1 M NL4-3 potently interfere with CD155 surface expression. Thus, Vpu seems to subvert NK cell responses against HIV-1 infected T cells by modulation of receptors necessary for NK cell activation. AU - Bolduan, S. AU - Reif, T.* AU - Schindler, M. AU - Schubert, U.* C1 - 31923 C2 - 34882 CY - San Diego SP - 375-384 TI - HIV-1 Vpu mediated downregulation of CD155 requires alanine residues 10, 14 and 18 of the transmembrane domain. JO - Virology VL - 464-465 IS - 1 PB - Academic Press Inc Elsevier Science PY - 2014 SN - 0042-6822 ER - TY - JOUR AB - The hepatitis B virus (HBV) is formed by budding. A stretch of 22 amino acids (aa) (matrix domain, MD, R103 - S124) in the large envelope protein L is crucial for virion formation and probably establishes contact to the nucleocapsid. Here, we assess the impact of sequence variations at numerous individual aa positions within the MD on virion formation. We generated panels of L mutants covering all 19 possible aa for 11 positions and tested the capacity of these mutants to rescue virus production by an L-defective HBV genome. At four positions (L112, R113, P117, W122), any replacement of the wild type (WT) aa reduced virus assembly to undetectable levels. Virus production was strongly diminished by substitutions at five other positions (R103, T106, S115, H116, A119). Only two tested positions (D114, Q118) tolerated several substitutions. The restricted positions may represent promising targets for the development of novel antiviral strategies. AU - Schittl, B. AU - Bruss, V. C1 - 31619 C2 - 34627 CY - San Diego SP - 183-189 TI - Mutational profiling of the variability of individual amino acid positions in the hepatitis B virus matrix domain. JO - Virology VL - 458-459 IS - 1 PB - Academic Press Inc Elsevier Science PY - 2014 SN - 0042-6822 ER - TY - JOUR AB - HIV-1 Vpu induces downregulation of cell surface NTB-A to evade lysis of HIV-1 infected cells by NK cells. Here we show that Vpu affects the anterograde transport and the glycosylation pattern of NTB-A by a mechanism that is distinct from the Vpu induced downregulation of CD4 and tetherin. In the presence of Vpu, only the high mannose form of NTB-A was detectable, suggesting that Vpu prevented the formation of the mature form of NTB-A. This phenomenon is associated with the ability of Vpu to downregulate cell surface NTB-A by retention of NTB-A within the Golgi-compartment. Furthermore, the Vpu-mediated effect on NTB-A glycosylation is highly conserved among Vpu proteins derived from HIV-1 and SIV and corresponds to the level of downregulation of NTB-A. Together, these results suggest that the reduction of NTB-A from the cell surface is associated with the Vpu-mediated effect on the glycosylation pattern of newly synthesized NTB-A molecules. AU - Bolduan, S.* AU - Hubel, P.* AU - Reif, T.* AU - Lodermeyer, V.* AU - Höhne, K. AU - Fritz, J.V.* AU - Sauter, D.* AU - Kirchhoff, F.* AU - Fackler, O.T.* AU - Schindler, M. AU - Schubert, U.* C1 - 25146 C2 - 31836 SP - 190-203 TI - HIV-1 Vpu affects the anterograde transport and the glycosylation pattern of NTB-A. JO - Virology VL - 440 IS - 2 PB - Academic Press - Elsevier PY - 2013 SN - 0042-6822 ER - TY - JOUR AB - The foot-and-mouth disease virus leader proteinase (Lb(pro)) cleaves itself off the nascent viral polyprotein. NMR studies on the monomeric variant Lb(pro) L200F provide structural evidence for intramolecular self-processing. N-15-HSQC measurements of Lb(pro) L200F showed specifically shifted backbone signals in the active and substrate binding sites compared to the monomeric variant sLb(pro), lacking six C-terminal residues. This indicates transient intramolecular interactions between the C-terminal extension (CTE) of one molecule and its own active site. Contrastingly, the porcine reproductive and respiratory syndrome virus (PRRSV) leader proteinase nsp1 alpha, with a papain-like fold like Lb(pro), stably binds its own CTE. Parts of the beta-sheet domains but none of the alpha-helical domains of Lb(pro) and nsp1 alpha superimpose; consequently, the alpha-helical domain of nsp1 alpha is oriented differently relative to its beta-sheet domain. This provides a large interaction surface for the CTE with the globular domain, stabilising the intramolecular complex. Consequently, self-processing inactivates nsp1 alpha but not Lb(pro). AU - Steinberger, J.* AU - Kontaxis, G.* AU - Rancan, C. AU - Skern, T.* C1 - 27184 C2 - 32579 SP - 271-277 TI - Comparison of self-processing of foot-and-mouth disease virus leader proteinase and porcine reproductive and respiratory syndrome virus leader proteinase nsp1α. JO - Virology VL - 443 IS - 2 PB - Academic Press Elsevier Science PY - 2013 SN - 0042-6822 ER - TY - JOUR AB - The Epstein-Barr virus (EBV) growth-transforms B-lymphocytes. The virus-encoded nuclear antigen 2 (EBNA2) is essential for transformation and activates gene expression by association with DNA-bound transcription factors such as RBPJκ (CSL/CBF1). We have previously shown that EBNA2 contains symmetrically dimethylated Arginine (sDMA) residues. Deletion of the RG-repeat results in a reduced ability of the virus to immortalise B-cells. We now show that the RG repeat also contains asymmetrically dimethylated Arginines (aDMA) but neither non-methylated (NMA) Arginines nor citrulline residues. We demonstrate that only aDMA-containing EBNA2 is found in a complex with DNA-bound RBPJκ in vitro and preferentially associates with the EBNA2-responsive EBV C, LMP1 and LMP2A promoters in vivo. Inhibition of methylation in EBV-infected cells results in reduced expression of the EBNA2-regulated viral gene LMP1, providing additional evidence that methylation is a prerequisite for DNA-binding by EBNA2 via association with the transcription factor RBPJκ. AU - Gross, H.* AU - Barth, S.* AU - Palermo, R.D.* AU - Mamiani, A.* AU - Hennard, C. AU - Zimber-Strobl, U. AU - West, M.J.* AU - Kremmer, E. AU - Grässer, F.A.* C1 - 219 C2 - 27015 SP - 299-310 TI - Asymmetric Arginine dimethylation of Epstein-Barr virus nuclear antigen 2 promotes DNA targeting. JO - Virology VL - 397 IS - 2 PB - Elsevier PY - 2010 SN - 0042-6822 ER - TY - JOUR AB - Here we report a novel strategy for the induction of CD8(+) T cell adaptive immune response against viral and tumor antigens. This approach relies on high levels of incorporation in HIV-1 VLPs of a mutant of HIV-1 Nef (Nef(mut)) which can act as anchoring element for foreign proteins. By in vitro assay, we found that VLP-associated Nef(mut) is efficiently cross-presented by antigen presenting cells. Inoculation in mice of VLPs incorporating the HPV-16 E7 protein fused to Nef(mut) led to an anti-E7 CD8(+) T cell response much stronger than that elicited by E7 recombinant protein inoculated with incomplete Freund's adjuvant and correlating with well-detectable anti-E7 CTL activity. Most relevantly, mice immunized with Nef(mut)-E7 VLPs developed a protective immune response against tumors induced by E7 expressing tumor cells. These results make Nef(mut) VLPs a promising candidate for new vaccine strategies focused on the induction of CD8(+) T cell immunity. AU - di Bonito, P.* AU - Grasso, F.* AU - Mochi, S.* AU - Petrone, L.* AU - Fanales-Belasio, E.* AU - Mei, A.* AU - Cesolini, A.* AU - Laconi, G.* AU - Conrad, H.* AU - Bernhard, H.* AU - Dembek, C.J. AU - Cosma, A. AU - Santini, S.M.* AU - Lapenta, C.* AU - Donati, S.* AU - Muratori, C.* AU - Giorgi, C.* AU - Federico, M.* C1 - 6084 C2 - 28024 SP - 45-55 TI - Anti-tumor CD8⁺ T cell immunity elicited by HIV-1-based virus-like particles incorporating HPV-16 E7 protein. JO - Virology VL - 395 IS - 1 PB - Elsevier PY - 2009 SN - 0042-6822 ER - TY - JOUR AB - Plant virus infection involves the production of viral small RNAs (vsRNAs) with the potential to associate with distinct Argonaute (AGO)-containing silencing complexes and mediate diverse silencing effects on RNA and chromatin. We used multiplexed, high-throughput pyrosequencing to profile populations of vsRNAs from plants infected with viruses from different genera. Sense and antisense vsRNAs of 20 to 24 nucleotides (nts) spread throughout the entire viral genomes in an overlapping configuration; virtually all genomic nucleotide positions were represented in the data set. We present evidence to Suggest that every genomic position could be a putative cleavage site for vsRNA formation, although viral genomes contain specific regions that serve as preferential sources of vsRNA production. Hotspots for vsRNAs of 21-, 22-, and 24-nt usually coincide in the same genomic regions, indicating similar target affinities among Dicer-like (DCL) enzymes. In the light Of Our results, the overall contribution of perfectly base paired (double-stranded RNA and imperfectly base paired structures within single-stranded RNA to vsRNA formation is discussed. Our census of vsRNAs extends the Current view of the distribution and composition of vsRNAs in virus-infected plants, and contributes to a better understanding of vsRNA biogenesis. AU - Donaire, L.* AU - Wang, Y. AU - Gonzalez-Ibeas, D.* AU - Mayer, K.F.X. AU - Aranda, M.A.* AU - Llave, C.* C1 - 551 C2 - 27006 CY - San Diego SP - 203-214 TI - Deep-sequencing of plant viral small RNAs reveals effective and widespread targeting of viral genomes. JO - Virology VL - 392 IS - 2 PB - Academic Press, Elsevier PY - 2009 SN - 0042-6822 ER - TY - JOUR AB - Recombinant herpesviruses are increasingly utilized to study herpesvirus biology. For recombinant viruses carrying insertions of foreign sequences, attenuated phenotypes in vivo have been frequently observed. In most cases, the underlying mechanisms were not clear or have not been investigated. In this study, we used a recombinant murine gammaherpesvirus 68 (MHV-68), carrying a cassette for the expression of the non-structural protein NS3 of Hepatitis C virus (MHV-68-NS3), to systematically address the question whether the insertion of a defined foreign sequence (NS3) interferes with the biological properties of the recombinant virus in vivo, and to analyze the underlying mechanism. We show that while MHV-68-NS3 is attenuated in vivo, recombinant MHV-68 carrying identical genomic inserts but unable to express the NS3 protein, are not attenuated. Moreover, we provide evidence that the attenuated phenotype of MHV-68-NS3 is caused by the immune response. Our findings are important for the in vivo use of recombinant MHV-68 carrying insertions of marker genes, reporter genes or genes of model antigens. They are also relevant for the potential application of MHV-68 as gene delivery vector. AU - El-Gogo, S.* AU - Flach, B.* AU - Staib, C.* AU - Sutter, G.* AU - Adler, H. C1 - 2481 C2 - 25613 SP - 322-327 TI - In vivo attenuation of recombinant murine gammaherpesvirus 68 (MHV-68) is due to the expression and immunogenicity but not to the insertion of foreign sequences. JO - Virology VL - 380 IS - 2 PB - Elsevier PY - 2008 SN - 0042-6822 ER - TY - JOUR AB - Three short (7 to 9 nucleotides) highly conserved nucleotide sequences were identified in the putative promoter regions (150 bp upstream and 50 bp downstream of the ATG translation start site) of three members of the genus Chlorovirus, family Phycodnaviridae. Most of these sequences occurred in similar locations within the defined promoter regions. The sequence and location of the motifs were often conserved among homologous ORFs within the Chlorovirus family. One of these conserved sequences (AATGACA) is predominately associated with genes expressed early in virus replication. AU - Fitzgerald, L.A.* AU - Boucher, P.T.* AU - Yanai-Balser, G.M.* AU - Suhre, K. AU - Graves, M.V.* AU - van Etten, J.L.* C1 - 1196 C2 - 25943 SP - 388-393 TI - Putative gene promoter sequences in the chlorella viruses. JO - Virology VL - 380 IS - 2 PB - Elsevier PY - 2008 SN - 0042-6822 ER - TY - JOUR AB - The latent membrane protein 1 (LMP1) of Epstein-Barr virus (EBV) transforms cells activating signal transduction pathways such as NF-kappaB, PI3-kinase, or c-Jun N-terminal kinase (JNK). Here, we investigated the functional role of the LMP1-induced JNK pathway in cell transformation. Expression of a novel dominant-negative JNK1 allele caused a block of proliferation in LMP1-transformed Rat1 fibroblasts. The JNK-specific inhibitor SP600125 reproduced this effect in Rat1-LMP1 cells and efficiently interfered with proliferation of EBV-transformed lymphoblastoid cells (LCLs). Inhibition of the LMP1-induced JNK pathway in LCLs caused the downregulation of c-Jun and Cdc2, the essential G2/M cell cycle kinase, which was accompanied by a cell cycle arrest of LCLs at G2/M phase transition. Moreover, SP600125 retarded tumor growth of LCLs in a xenograft model in SCID mice. Our data support a critical role of the LMP1-induced JNK pathway for proliferation of LMP1-transformed cells and characterize JNK as a potential target for intervention against EBV-induced malignancies. AU - Kutz, H. AU - Reisbach, G. AU - Schultheiss, U. AU - Kieser, A. C1 - 1008 C2 - 25414 SP - 246-256 TI - The c-Jun N-terminal kinase pathway is critical for cell transformation by the latent membrane protein 1 of Epstein-Barr virus. JO - Virology VL - 371 IS - 2 PB - Elsevier PY - 2008 SN - 0042-6822 ER - TY - JOUR AB - We previously identified an RNA transport element (RTE) present at a high copy number in the mouse genome. Here, we show that a related element, RTE-D, is part of a mobile LTR-retrotransposon, which belongs to a family of intracisternal A-particle related elements (IAP). We demonstrate that RTE-D is essential for the mobility of the retrotransposon and it can be substituted by other known RNA export signals. RTE-deficient IAP transcripts are retained in the nucleus, while the RTE-containing transcripts accumulate in the cytoplasm allowing Gag protein expression. RTE-D acts as a posttranscriptional control element in a heterologous reporter mRNA and is activated by the cellular RNA binding protein 15 (RBM15), as reported for the previously described RTE. We identified a complex family of RTE-containing IAPs in mouse and mapped the active RTE-D-containing IAPs to the Mmr10 group of LTR-retrotransposons. These data reveal that, despite a complex evolutionary history, retroelements and retroviruses share the dependency on posttranscriptional regulation. AU - Zolotukhin, A.S.* AU - Schneider, R. AU - Uranishi, H.* AU - Bear, J.* AU - Tretyakova, I.* AU - Michalowski, D.* AU - Smulevitch, S.* AU - O'Keeffe, S. AU - Pavlakis, G.N.* AU - Felber, B.K.* C1 - 3269 C2 - 25387 SP - 88-99 TI - The RNA transport element RTE is essential for IAP LTR-retrotransposon mobility. JO - Virology VL - 377 IS - 1 PB - Elsevier PY - 2008 SN - 0042-6822 ER - TY - JOUR AB - This study investigates the role of the proviral transcriptional enhancer for B-lymphoma induction by exogenous Akv murine leukemia virus. Infection of newborn inbred NMRI mice with Akv induced 35% plasma cell proliferations (PCPs) (consistent with plasmacytoma), 33% diffuse large B-cell lymphomas, 25% follicular B-cell lymphomas and few splenic marginal zone and small B-cell lymphomas. Deleting one copy of the 99-bp proviral enhancer sequence still allowed induction of multiple B-cell tumor types, although PCPs dominated (77%). Additional mutation of binding sites for the glucocorticoid receptor, Ets, Runx, or basic helix–loop–helix transcription factors in the proviral U3 region, however, shifted disease induction to almost exclusively PCPs, but had no major influence on tumor latency periods. Southern analysis of immunoglobulin rearrangements and ecotropic provirus integration patterns showed that many of the tumors/cell proliferations induced by each virus were polyclonal. Our results indicate that enhancer mutations weaken the ability of Akv to induce mature B-cell lymphomas prior to the plasma cell stage, whereas development of plasma cell proliferations is less dependent of viral enhancer strength. AU - Sorensen, K.D.* AU - Kunder, S. AU - Quintanilla-Martinez, L. AU - Sorensen, J. AU - Schmidt, J. AU - Pedersen, F.S.* C1 - 2369 C2 - 24362 SP - 179-191 TI - Enhancer mutations of Akv murine leukemia virus inhibit the induction of mature B-cell lymphomas and shift disease specificity towards the more differentiated plasma cell stage. JO - Virology VL - 362 IS - 1 PB - Elsevier PY - 2007 SN - 0042-6822 ER - TY - JOUR AU - Kastenmüller, W. AU - Drexler, I. AU - Ludwig, H. AU - Erfle, V. AU - Peschel, C.* AU - Bernhard, H.* AU - Sutter, G. C1 - 1814 C2 - 23951 SP - 276-288 TI - Infection of human dendritic cells with recombinant vaccinia virus MVA reveals general persistence of viral early transcription but distinct maturation-dependent cytopathogenicity. JO - Virology VL - 350 PY - 2006 SN - 0042-6822 ER - TY - JOUR AU - Ma, S.L.* AU - Sorensen, A.B.* AU - Kunder, S.K.L. AU - Sorensen, K.D.* AU - Quintanilla-Martinez, L. AU - Morris, D.W.* AU - Schmidt, J. AU - Pedersen, F.S.* C1 - 483 C2 - 23923 SP - 306-318 TI - The Icsbp locus is a common proviral insertion site in mature B-cell lymphomas/plasmacytomas induced by exogenous murine leukemia virus. JO - Virology VL - 352 PY - 2006 SN - 0042-6822 ER - TY - JOUR AU - Collin, N.* AU - Guérin, J.-L.* AU - Drexler, I. AU - Blanié, S.* AU - Gelfi, J.* AU - Boullier, S.* AU - Foucras, G.* AU - Sutter, G. AU - Messud-Petit, F.* C1 - 4481 C2 - 23186 SP - 171-178 TI - The poxviral scrapin MV-LAP requires a myxoma viral infection context to efficiently downregulate MHC-I molecules. JO - Virology VL - 343 PY - 2005 SN - 0042-6822 ER - TY - JOUR AU - Greenwood, A.D.* AU - Stengel, A. AU - Erfle, V. AU - Seifarth, W.* AU - Leib-Mösch, C. C1 - 1991 C2 - 22780 SP - 203-213 TI - The distribution of pol containing human endogenous retroviruses in non-human primates. JO - Virology VL - 334 PY - 2005 SN - 0042-6822 ER - TY - JOUR AU - Rasmussen, M.H.* AU - Sorensen, A.B.* AU - Morris, D.W.* AU - Dutra, J.C.* AU - Engelhard, E.K.* AU - Wang, C.L.* AU - Schmidt, J. AU - Pedersen, F.S.* C1 - 3890 C2 - 23188 SP - 353-364 TI - Tumor model-specific proviral insertional mutagenesis of the Fos/Jdp2/batf locus. JO - Virology VL - 337 PY - 2005 SN - 0042-6822 ER - TY - JOUR AU - Sørensen, K.D.* AU - Sørensen, A.B.* AU - Quintanilla-Martinez, L. AU - Kunder, S. AU - Schmidt, J. AU - Pedersen, F.S.* C1 - 2267 C2 - 22699 SP - 234-244 TI - Distinct roles of enhancer nuclear factor 1 (NF1) sites in plasmacytoma and osteopetrosis induction by Akv1-99 murine leukemia virus. JO - Virology VL - 334 PY - 2005 SN - 0042-6822 ER - TY - JOUR AU - Ma, S.L.* AU - Lovmand, J.* AU - Sorensen, A.B.* AU - Luz, A. AU - Schmidt, J. AU - Pedersen, F.S.* C1 - 22377 C2 - 21291 SP - 638-644 TI - Triple basepair changes within and adjacent to the conserved YY1 motif upstream of the U3 enhancer repeats SL3-3 murine leukemia virus cause a small but significant shortening of latency of T-lymphoma induction. JO - Virology VL - 313 PY - 2003 SN - 0042-6822 ER - TY - JOUR AB - Evolution over millions of years has adapted several thousand copies of retrovirus-like elements and over 10 times as many solitary long terminal repeats (LTRs) to their present location in the human genome. Transcription of these human endogenous retroviruses (HERVs) has been detected in various cells and tissues, and in some cases their transcriptional control elements have been recruited by cellular genes. We used a retroviral pol-specific expression array to obtain a HERV transcription profile in a variety of human cells such as epidermal keratinocytes, liver cells, kidney cells, pancreatic cells, lymphocytes, and lung fibroblasts. This rapid screening test revealed a distinct HERV pol-expression pattern in each cell type tested so far. About 40 different U3/R regulatory sequences from the HERV-H and HERV-W families were then amplified from actively transcribed 3'HERV LTRs of various cell lines and tissues. Their promoter activities were compared with LTR sequences of other known HERV families in 12 human cell lines using a transient luciferase reporter system. Expression of the isolated HERV LTRs varied significantly in these cell lines, in some cases showing strict cell type specificity. These results suggest that endogenous retroviral LTRs may be a valuable source of transcriptional regulatory elements for the construction of targeted retroviral expression vectors. AU - Schön, U. AU - Seifarth, W.* AU - Baust, C.* AU - Hohenadl, C. AU - Erfle, V. AU - Leib-Mösch, C. C1 - 9502 C2 - 19694 SP - 280-291 TI - Cell Type-Specific Expression and Promoter Activity of Human Endogenous Retroviral Long Terminal Repeats. JO - Virology VL - 279 IS - 1 PB - Academic Press Inc. PY - 2001 SN - 0042-6822 ER - TY - JOUR AB - We describe the identification and functional analysis of an evolutionary distinct new avian hepadnavirus. Infection of snow geese (Anser caerulescens) with a duck hepatitis B virus (DHBV)-related virus, designated SGHBV, was demonstrated by detection of envelope proteins in sera with anti- DHBV preS and S antibodies. Comparative sequence analysis of the PCR- amplified SGHBV genomes revealed unique SGHBV sequence features compared with other avian hepadnaviruses. Unlike DHBV, SGHBV shows an open reading frame in an analogous position to orthohepadnavirus X genes. Four of five cloned genomes were competent in replication, gene expression, and virus particle secretion in chicken hepatoma cells. Primary duck hepatocytes were permissive for infection with SGHBV, suggesting a similar or identical host range. SGHBV was found to secrete a significant fraction of virion-like particles containing single-stranded viral DNA. This was observed both in cell culture medium of SGHBV DNA-transfected LMH cells and in viremic sera of several birds, suggesting that it is a stable trait of SGHBV. Taken together, SGHBV has several unique features that expand the knowledge of the functional and evolutionary diversity of hepadnaviruses and offers new experimental opportunities for studies on the life cycle of hepadnaviruses. AU - Chang, S.* AU - Netter, H.J.* AU - Bruns, M.P.* AU - Schneider, R. AU - Frölich, K.* AU - Will, H.* C1 - 33206 C2 - 35621 SP - 39-54 TI - A new avian hepadnavirus infecting snow geese (Anser caerulescens) produces a significant fraction of virions containing single-stranded DNA. JO - Virology VL - 262 IS - 1 PY - 1999 SN - 0042-6822 ER - TY - JOUR AB - hMt-c-fos-LTR transgenic mice (U. Rüther, D. Komitowski, F. R. Schubert, and E. F. Wagner. Oncogene 4, 861-865, 1989) developed bone sarcomas in 20% (3/15) of females at 448 +/- 25 days and in 8% (1/12) of males at 523 days. After infection of newborns with Akv, an infectious retrovirus derived from the ecotropic provirus of the AKR mouse, 69% (20/28) of female animals and 83% (24/29) of males developed malignant fibrous-osseous tumors. The tumors in infected transgenics developed with higher frequency and a 200-days shorter mean tumor latency period. The hMt-c-fos-LTR transgene was expressed in all the fibrous-osseous tumors. They also showed newly integrated Akv proviruses, but in most tumors Akv was detected and expressed in only a small number of the tumor cells. Wild-type C3H mice infected with Akv developed benign osteomas with an incidence of 33% and a latency period of 474 days. The data indicate that Akv exerts distinct pathogenic effects on the skeleton. In hMt-c-fos-LTR transgenic mice, predisposed to bone sarcomagenesis, Akv acts synergistically with the fos transgene, resulting in the development of fibrous-osseous tumors. AU - Schmidt, J. AU - Krump-Konvalinkova, V.* AU - Luz, A. AU - Goralczyk, R. AU - Snell, G. AU - Wendel, S. AU - Dorn, S. AU - Pedersen, L.* AU - Strauss, P.G.* AU - Erfle, V. C1 - 27596 C2 - 32758 SP - 85-92 TI - Akv murine leukemia virus enhances bone tumorigenesis in hMT-c-fos-LTR transgenic mice. JO - Virology VL - 206 IS - 1 PB - Academic Press PY - 1995 SN - 0042-6822 ER - TY - JOUR AB - The contribution of endogenous retroviruses to the multistep process of lymphomagenesis was investigated in wild-type mice and in two different myc-kappa transgenic mouse lines by infection with Akv. This retrovirus is derived from the endogenous ecotropic provirus of the AKR mouse and was previously considered to be nonlymphomagenic. The mice of the two myc-k transgenic lines are predisposed to B-cell lymphomagenesis and were therefore considered to be more susceptible to Akv. For comparison, the same mouse strains were also infected with the exogenous Moloney murine leukemia virus (MoMuLV). Both MoMuLV and Akv increased the tumor incidence and shortened the tumor latency period in wild-type mice and in the transgenic mouse lines. The differences in pathogenicity, number of provirus integrations, and level of virus expression between MoMuLV and Akv indicate different mechanisms of lymphomagenesis: while MoMuLV induced tumors apparently by insertional mutagenesis involving common integration sites similar to previous reports, the enhancement of lymphomagenesis by Akv seems to be directed by other mechanisms. AU - Speth, C. AU - Luz, A. AU - Strauss, P.G. AU - Wendel, S. AU - Zeidler, R.* AU - Dorn, S. AU - Erfle, V. AU - Brem, G.* AU - Lipp, M.* AU - Schmidt, J. C1 - 27598 C2 - 32759 SP - 93-99 TI - Akv murine leukemia virus enhances lymphomagenesis in myc-κ transgenic and in wild-type mice. JO - Virology VL - 206 IS - 1 PB - Academic Press PY - 1995 SN - 0042-6822 ER - TY - JOUR AB - The mammalian genome harbors a large number of endogenous retroviruses and retrovirus-like elements. Increasing evidence is found that such elements can be activated and act as insertional mutagens. The activation of endogenous retroviral elements can be induced by a variety of environmental factors including irradiation. We have observed the insertion of a murine endogenous retrovirus-like ETn element into intron 4 of the p53 gene in an osteosarcoma cell line derived from a radiation-induced osteosarcoma. The insertion resulted in a p53-ETn-p53 fusion mRNA, a novel form of p53 mutation. This is the first report on insertion of an endogenous retroviral element into the p53 tumor suppressor gene. The data suggest that activated endogenous retroviruses and retrovirus-like elements might pose an enhanced risk for individuals exposed to noxae, which activate endogenous retroviral elements. AU - Mitreiter, K. AU - Schmidt, J. AU - Luz, A. AU - Atkinson, M.J. AU - Höfler, H.H. AU - Erfle, V.F. AU - Strauß, P.G. C1 - 33251 C2 - 38947 SP - 837-841 TI - Disruption of the murine p53 gene by insertion of an endogenous retrovirus-like element (ETn) in a cell line from radiation-induced osteosarcoma. JO - Virology VL - 200 IS - 2 PY - 1994 SN - 0042-6822 ER - TY - JOUR AU - Grässer, F.A. AU - Sauder, C. AU - Haiss, P. AU - Hille, A. AU - König, S. AU - Göttel, S. AU - Kremmer, E. AU - Leinenbach, H.P. AU - Zeppezauer, M. AU - Müller-Lantzsch, N. C1 - 20600 C2 - 13811 SP - 550-560 TI - Immunological Detection of Proteins Associated with the Epstein-Barr Virus Nuclear Antigen 2A (EBNA-2A). JO - Virology VL - 195 PY - 1993 SN - 0042-6822 ER - TY - JOUR AB - Recombinant baculoviruses containing the complete LMP and truncated LIMP genes were generated and high levels of the LMP proteins were expressed in Spadoptera Frugiperda insect cells. A specific rabbit antiserum directed against the N-terminal part of LMP was obtained by immunizing the rabbits with Escherichia coli-expressed trpE-N-terminal part of LMP fusion protein. A total of 127 human sera were studied for their immune response to the recombinant full-length LMP. In immunofluorescence analysis, all sera tested showed no detectable reaction with the recombinant full-length LMP. In immunoprecipitation-immunoblotting analysis, however, sera from patients with nasopharyngeal carcinoma ( 5 22), patients with Hodgkin's disease ( 16 27), patients with other diseases exhibiting high EA-IgG titers ( 3 52), and VCA-IgG-positive healthy individuals ( 2 26) were shown to contain antibodies against this recombinant LMP. The expressed LMP proteins provided a sufficient and economic source of the proteins for further serological and biological studies. AU - Chen, H.* AU - Kevan-Jah, S.* AU - Suentzenich, K.O. AU - Grässer, F.A.* AU - Mueller- Lantzsch, N.G.* C1 - 40669 C2 - 38886 SP - 106-115 TI - Expression of the Epstein-Barr virus latent membrane protein (LMP) in insect cells and detection of antibodies in human sera against this protein. JO - Virology VL - 190 IS - 1 PY - 1992 SN - 0042-6822 ER - TY - JOUR AB - N-tropic murine leukemia viruses have been observed in connection with radiation-induced osteosarcomagenesis in BALB/c mice. We have investigated the bone disease-inducing potential of molecularly cloned, BALB/c-derived N-tropic viruses in the random-bred NMRI mouse strain. The germ-line virus and an exogenous virus isolate were found to induce high incidences of osteopetrosis and lymphomas and a lower incidence of osteomas. Two viruses derived from somatically acquired proviruses of independent radiation-induced osteosarcomas induced lower incidences of osteopetrosis and lymphomas. Nucleotide sequence analysis of the long terminal repeat regions and RNase T1 fingerprint analysis revealed only few differences between the isolates. The possible involvement of N-tropic murine leukemia viruses in radiation-induced osteosarcomagenesis in the BALB/c mouse strain is discussed. AU - Pedersen, L.M.* AU - Strauß, P.G. AU - Schmidt, J. AU - Luz, A. AU - Erfle, V.F. AU - JÕrgensen, P.J.* AU - Kjeldgaard, N.O.* AU - Pedersen, F.S.* C1 - 41987 C2 - 40148 SP - 931-935 TI - Pathogenicity of BALB/c-derived N-tropic murine leukemia viruses. JO - Virology VL - 179 IS - 2 PY - 1990 SN - 0042-6822 ER - TY - JOUR AB - Human endogenous retroviral element S71 had previously been shown to contain gag- and pol-related regions and a 3′ LTR-like sequence. The nucleotide sequence of S71 was determined and compared with the corresponding regions of SSV and its helper virus SSAV. The 1.48-kb S71 gag region consists of matrix protein p15 (MA)-, capsid protein p30 (CA)-, and nucleocapsid protein p10 (NC)-related sections and the 1.82-kb pol region of tether, RNase H (RH), and endonuclease/integrase (IN) sections. The S71 nucleotide sequence contains a 167 amino acid open reading frame encompassing MA. The boundaries of the S71 element are delimited by direct repeats and the entire element is 5.4 kb long. Similarity between S71 and the v-sis-bearing, defective SSV provirus also covers overall structural organization, including the presence of presumably nonretroviral sequences. Both the gag and the pol regions of S71 contain sequences highly conserved in numerous retroviruses. Phylogenetic analysis with conserved CA, RH, and IN sequences showed that of all other (C-type) human retroviral elements available for comparison, S71 is most closely related to infectious primate and murine retroviruses. This suggests that S71 represents a phylogenetic subgroup of its own. In addition we identified short ranges of conserved amino acid sequences within C-type retroviral gag and pol genes sufficient for phylogenetic analysis. Use of these may facilitate large-scale phylogenetic evaluation of C-type retroviral elements and allow rapid classification of new elements. AU - Werner, T. AU - Brack-Werner, R. AU - Leib-Mösch, C. AU - Backhaus, H.* AU - Erfle, V.F. AU - Hehlmann., R.* C1 - 41861 C2 - 36465 SP - 225-238 TI - S71 is a phylogenetically distinct human endogenous retroviral element with structural and sequence homology to simian sarcoma virus (SSV). JO - Virology VL - 174 IS - 1 PY - 1990 SN - 0042-6822 ER - TY - JOUR AB - We have found human DNA to contain a number of sequences related to simian sarcoma associated virus (SSAV). One of these sequences was isolated from a human genomic library. The molecular clone, termed S71, contains regions homologous to SSAV gag and pol fragments and SSAV LTR. Furthermore, hybridization experiments and DNA sequencing revealed distinct homologies to the reverse transcriptase coding region of several other retroviruses including baboon endogenous virus (BaEV) and murine leukemia viruses (MuLV) as well as retrovirus-like elements. Some sequence homology was also found with the C-type retrovirus-related multicopy human clone 4-1. S71 is present in only one copy per human genome equivalent and exhibits an EcoRI restriction fragment length polymorphism. AU - Leib-Mösch, C.* AU - Brack, R. AU - Werner, T. AU - Erfle, V.F. AU - Hehlmann., R.* C1 - 41291 C2 - 36093 SP - 666-677 TI - Isolation of an SSAV-related endogenous sequence from human DNA. JO - Virology VL - 155 IS - 2 PY - 1986 SN - 0042-6822 ER - TY - JOUR AB - An N-ecotropic murine leukemia virus (OA MuLV), originally isolated from spontaneous osteomas of strain 101 mice, was molecularly cloned. The virus induces osteomas, osteopetrosis, and malignant lymphomas in NMRI mice. The cloned virus was analyzed by heteroduplex analysis, restriction enzyme mapping, and oligonucleotide mapping. The data show a very close relationship to the endogenous Akv prototype virus with some differences in the gag and the env region. The nucleotide sequence of the U3 region of OA MuLV LTR revealed a structure within the presumable enhancer region very similar to the U3 sequences of the FBJ murine sarcoma virus and its associated helper virus. The significance of these specific structures for the oncogenicity of the virus and the development of the typical disease pattern is discussed. AU - Leib-Mösch, C.* AU - Schmidt, J. AU - Etzerodt, M.* AU - Pedersen, F.S.* AU - Hehlmann., R.* AU - Erfle, V.F. C1 - 41360 C2 - 36101 SP - 96-105 TI - Oncogenic retrovirus from spontaneous murine osteomas : II. Molecular cloning and genomic characterization. JO - Virology VL - 150 IS - 1 PY - 1986 SN - 0042-6822 ER -