TY  - JOUR
AB  - Since its discovery in 1965, our understanding of the hepatitis B virus (HBV) replication cycle and host immune responses has increased markedly. In contrast, our knowledge of the molecular biology of hepatitis delta virus (HDV), which is associated with more severe liver disease, is less well understood. Despite the progress made, critical gaps remain in our knowledge of HBV and HDV replication and the mechanisms underlying viral persistence and evasion of host immunity. The International HBV Meeting is the leading annual scientific meeting for presenting the latest advances in HBV and HDV molecular virology, immunology, and epidemiology. In 2023, the annual scientific meeting was held in Kobe, Japan and this review summarises some of the advances presented at the Meeting and lists gaps in our knowledge that may facilitate the development of new therapies.
AU  - HBV2023*
AU  - Allweiss, L.*
AU  - Cohen, C.*
AU  - Dias, J.M.L.*
AU  - Fumagalli, V.*
AU  - Guo, H.*
AU  - Harris, J.M.*
AU  - Hu, J.*
AU  - Iannacone, M.*
AU  - Isogawa, M.*
AU  - Jeng, W.J.*
AU  - Kim, K.H.*
AU  - Kramvis, A.*
AU  - Li, W.*
AU  - Lucifora, J.*
AU  - Muramatsu, M.*
AU  - Neuveut, C.*
AU  - Ploss, A.*
AU  - Pollicino, T.*
AU  - Protzer, U.
AU  - Tan, A.*
AU  - Tanaka, Y.*
AU  - Tu, T.*
AU  - Tsukuda, S.*
AU  - Thimme, R.*
AU  - Urban, S.*
AU  - Watashi, K.*
AU  - Yuan, Z.*
AU  - Yeh, S.H.*
AU  - McKeating, J.A.*
AU  - Revill, P.A.*
C1  - 70693
C2  - 55713
TI  - Highlights from the 2023 international meeting on the molecular biology of hepatitis B virus.
JO  - J. Gen. Virol.
VL  - 105
IS  - 5
PY  - 2024
SN  - 0022-1317
ER  - 

TY  - JOUR
AB  - Murine gammaherpesvirus 68 (MHV-68), a widely used small-animal model for the analysis of gammaherpesvirus pathogenesis, encodes the MHV-68-specific ORFs M12 and M13. The function of M12 and M13 has not been investigated so far. Therefore, we constructed and analysed recombinant MHV-68 with mutations in either M12, M13 or M12/M13. Both the M12 and M13 mutants did not display any phenotype in vitro or in vivo. However, although the M12/13 double mutant showed similar lytic growth in fibroblasts in vitro and in the lungs of infected mice as wild-type MHV-68, it was significantly attenuated in vivo during latency. This phenotype was completely restored in a revertant of the M12/13 double mutant. Thus, it appears that M12 and M13 might have redundant functions that are only revealed if both genes are lacking. The observation that M12/13 have a function during latency not only contributes to the further understanding of the pathogenesis of MHV-68 infection but might also be of interest considering that M12/13 are located at a genomic position similar to that of LMP2A and K15. The latter are important proteins of their respective human gammaherpesviruses EBV and KSHV that contribute to cellular survival, cell activation and proliferation, which was deduced from in vitro studies.
AU  - Steer, B.
AU  - Adler, B.*
AU  - Adler, H.
C1  - 68020
C2  - 54498
CY  - 14-16 Meredith St, London, England
TI  - Open reading frames M12/M13 jointly contribute to MHV-68 latency.
JO  - J. Gen. Virol.
VL  - 104
IS  - 8
PB  - Microbiology Soc
PY  - 2023
SN  - 0022-1317
ER  - 

TY  - JOUR
AB  - A number of seroassays are available for SARS-CoV-2 testing; yet, head-to-head evaluations of different testing principles are limited, especially using raw values rather than categorical data. In addition, identifying correlates of protection is of utmost importance, and comparisons of available testing systems with functional assays, such as direct viral neutralisation, are needed.We analysed 6658 samples consisting of true-positives (n=193), true-negatives (n=1091), and specimens of unknown status (n=5374). For primary testing, we used Euroimmun-Anti-SARS-CoV-2-ELISA-IgA/IgG and Roche-Elecsys-Anti-SARS-CoV-2. Subsequently virus-neutralisation, GeneScriptcPass, VIRAMED-SARS-CoV-2-ViraChip, and Mikrogen-recomLine-SARS-CoV-2-IgG were applied for confirmatory testing. Statistical modelling generated optimised assay cut-off thresholds. Sensitivity of Euroimmun-anti-S1-IgA was 64.8%, specificity 93.3% (manufacturer's cut-off); for Euroimmun-anti-S1-IgG, sensitivity was 77.2/79.8% (manufacturer's/optimised cut-offs), specificity 98.0/97.8%; Roche-anti-N sensitivity was 85.5/88.6%, specificity 99.8/99.7%. In true-positives, mean and median Euroimmun-anti-S1-IgA and -IgG titres decreased 30/90 days after RT-PCR-positivity, Roche-anti-N titres decreased significantly later. Virus-neutralisation was 80.6% sensitive, 100.0% specific (≥1:5 dilution). Neutralisation surrogate tests (GeneScriptcPass, Mikrogen-recomLine-RBD) were >94.9% sensitive and >98.1% specific. Optimised cut-offs improved test performances of several tests. Confirmatory testing with virus-neutralisation might be complemented with GeneScriptcPassTM or recomLine-RBD for certain applications. Head-to-head comparisons given here aim to contribute to the refinement of testing strategies for individual and public health use.
AU  - Olbrich, L.*
AU  - Castelletti, N.
AU  - Schälte, Y.
AU  - Garí, M.
AU  - Pütz, P.
AU  - Bakuli, A.*
AU  - Pritsch, M.*
AU  - Kroidl, I.*
AU  - Saathoff, E.*
AU  - Guggenbüehl Noller, J.M.*
AU  - Fingerle, V.*
AU  - Le Gleut, R.
AU  - Gilberg, L.*
AU  - Brand, I.*
AU  - Falk, P.*
AU  - Markgraf, A.*
AU  - Deák, F.*
AU  - Riess, F.*
AU  - Diefenbach, M.*
AU  - Eser, T.*
AU  - Weinauer, F.*
AU  - Martin, S.*
AU  - Quenzel, E.M.*
AU  - Becker, M.*
AU  - Durner, J.*
AU  - Girl, P.*
AU  - Müller, K.*
AU  - Radon, K.*
AU  - Fuchs, C.
AU  - Wölfel, R.*
AU  - Hasenauer, J.
AU  - Hoelscher, M.*
AU  - Wieser, A.*
C1  - 63293
C2  - 51261
TI  - Head-to-head evaluation of seven different seroassays including direct viral neutralisation in a representative cohort for SARS-CoV-2.
JO  - J. Gen. Virol.
VL  - 102
IS  - 10
PY  - 2021
SN  - 0022-1317
ER  - 

TY  - JOUR
AB  - Infections with human herpesviruses share several molecular characteristics, but the diversified medical outcomes are distinct to viral subfamilies and species. Notably, both clinical and molecular correlates of infection are a challenging field and distinct patterns of virus-host interaction have rarely been defined: this study therefore focuses on the search for virus-specific molecular indicators. As previous studies have demonstrated the impact of herpesvirus infections on changes in host signalling path- ways, we illustrate virus-modulated expression levels of individual cellular protein kinases. Current data reveal (i) alpha- and beta-, gamma-herpesvirus-specific patterns of kinase modulation as well as (ii) differential levels of up-/downregulated kinase expression and phosphorylation, which collectively suggest (iii) defined signalling patterns specific for the various viruses (VSS) that may prove useful for defining molecular indicators. Combined, the study confirms the correlation between herpesviral replication and modulation of signalling kinases, possibly exploitable for the in vitro characterization of viral infections.
AU  - Marschall, M.*
AU  - Strojan, H.*
AU  - Kiener, R.*
AU  - Wangen, C.*
AU  - Sonntag, E.*
AU  - Müller, R.*
AU  - Zeitträger, I.*
AU  - Wagner, S.*
AU  - Stamminger, T.*
AU  - Milbradt, J.*
AU  - Behrends, U.
AU  - Körber, N.
AU  - Bauer, T.
AU  - Schrödel, S.*
AU  - Thirion, C.*
AU  - Wagner, R.*
AU  - Hutterer, C.*
C1  - 57876
C2  - 48160
CY  - Charles Darwin House, 12 Roger St, London Wc1n 2ju, Erks, England
SP  - 284-289
TI  - Differential upregulation of host cell protein kinases by the replication of α-, β- and γ-Herpesviruses provides a signature o virus-specific signalling.
JO  - J. Gen. Virol.
VL  - 101
IS  - 3
PB  - Microbiology Soc
PY  - 2020
SN  - 0022-1317
ER  - 

TY  - JOUR
AB  - Hepatitis B virus (HBV) is the prototype member of the family Hepadnaviridae and replicates via episomal copies of a covalently closed circular DNA (cccDNA) genome of approximately 3.2 kb. The chromatinization of this small viral genome, with overlapping open reading frames and regulatory elements, suggests an important role for epigenetic pathways to regulate HBV transcription. However, the host pathways that regulate HBV transcription and the temporal nature of promoter usage in infected cells are not well understood, in part due to the compact genome structure and overlapping open reading frames. To address this we developed a simple and cost-effective PCR assay to quantify the major viral RNAs and validated this technique using current state-of-art de novo HBV infection model systems. Our PCR method is three orders of magnitude more sensitive than Northern blot and requires relatively small amounts of starting material, making this an attractive tool for assessing HBV transcription.
AU  - D'Arienzo, V.*
AU  - Magri, A.*
AU  - Harris, J.M.*
AU  - Wing, P.A.C.*
AU  - Ko, C.
AU  - Rubio, C.O.*
AU  - Revill, P.A.*
AU  - Protzer, U.
AU  - Balfe, P.*
AU  - McKeating, J.A.*
C1  - 57639
C2  - 47924
CY  - Charles Darwin House, 12 Roger St, London Wc1n 2ju, Erks, England
TI  - A PCR assay to quantify patterns of HBV transcription.
JO  - J. Gen. Virol.
VL  - 102
IS  - 3
PB  - Microbiology Soc
PY  - 2019
SN  - 0022-1317
ER  - 

TY  - JOUR
AB  - A first step towards the development of a human immunodeficiency virus (HIV) animal model has been the identification and surmounting of species-specific barriers encountered by HIV along its replication cycle in cells from small animals. Serine incorporator proteins 3 (SERINC3) and 5 (SERINC5) were recently identified as restriction factors that reduce HIV-1 infectivity. Here, we compared the antiviral activity of SERINC3 and SERINC5 among mice, rats and rabbits, and their susceptibility to viral counteraction to their human counterparts. In the absence of viral antagonists, rodent and lagomorph SERINC3 and SERINC5 displayed anti-HIV activity in a similar range to human controls. Vesicular stomatitis virus G protein (VSV-G) pseudotyped virions were considerably less sensitive to restriction by all SERINC3/5 orthologs. Interestingly, HIV-1 Nef, murine leukemia virus (MLV) GlycoGag and equine infectious anemia virus (EIAV) S2 counteracted the antiviral activity of all SERINC3/5 orthologs with similar efficiency. Our results demonstrate that the antiviral activity of SERINC3/5 proteins is conserved in rodents and rabbits, and can be overcome by all three previously reported viral antagonists.
AU  - de Sousa-Pereira, P.
AU  - Abrantes, J.*
AU  - Bauernfried, S.*
AU  - Pierini, V.*
AU  - Esteves, P.J.*
AU  - Keppler, O.T.
AU  - Pizzato, M.*
AU  - Hornung, V.*
AU  - Fackler, O.T.*
AU  - Baldauf, H.-M.
C1  - 55452
C2  - 46158
SP  - 278-288
TI  - The antiviral activity of rodent and lagomorph SERINC3 and SERINC5 is counteracted by known viral antagonists.
JO  - J. Gen. Virol.
VL  - 100
IS  - 2
PY  - 2019
SN  - 0022-1317
ER  - 

TY  - JOUR
AB  - The Epstein-Barr virus is a human herpes virus with oncogenic potential. The virus-encoded nuclear antigen 2 (EBNA2) is a key mediator of viral tumorigenesis. EBNA2 features an arginine-glycine (RG) repeat at amino acids (aa)339-354 that is essential for the transformation of lymphocytes and contains symmetrically (SDMA) and asymmetrically (ADMA) di-methylated arginine residues. The SDMA-modified EBNA2 binds the survival motor neuron protein (SMN), thus mimicking SMD3, a cellular SDMA-containing protein that interacts with SMN. Accordingly, a monoclonal antibody (mAb) specific for the SDMA-modified RG repeat of EBNA2 also binds to SMD3. With the novel mAb 19D4 we now show that EBNA2 contains mono-methylated arginine (MMA) residues within the RG repeat. Using 19D4, we immune-precipitated and analysed by mass spectrometry cellular proteins in EBV-transformed B-cells that feature MMA motifs that are similar to the one in EBNA2. Among the cellular proteins identified, we confirmed by immunoprecipitation and/or Western blot analyses Aly/REF, Coilin, DDX5, FXR1, HNRNPK, LSM4, MRE11, NRIP, nucleolin, PRPF8, RBM26, SMD1 (SNRDP1) and THRAP3 proteins that are either known to contain MMA residues or feature RG repeat sequences that probably serve as methylation substrates. The identified proteins are involved in splicing, tumorigenesis, transcriptional activation, DNA stability and RNA processing or export. Furthermore, we found that several proteins involved in energy metabolism are associated with MMA-modified proteins. Interestingly, the viral EBNA1 protein that features methylated RG repeat motifs also reacted with the antibodies. Our results indicate that the region between aa 34-52 of EBNA1 contains ADMA or SDMA residues, while the region between aa 328-377 mainly contains MMA residues.
AU  - Ayoubian, H.*
AU  - Fröhlich, T.*
AU  - Pogodski, D.*
AU  - Flatley, A.
AU  - Kremmer, E.
AU  - Schepers, A.
AU  - Feederle, R.
AU  - Arnold, G.J.*
AU  - Grässer, F.A.*
C1  - 51646
C2  - 43406
CY  - London
SP  - 2128-2142
TI  - Antibodies against the mono-methylated arginine-glycine repeat (MMA-RG) of the Epstein-Barr virus nuclear antigen 2 (EBNA2) identify potential cellular proteins targeted in viral transformation.
JO  - J. Gen. Virol.
VL  - 98
IS  - 8
PB  - Microbiology Soc
PY  - 2017
SN  - 0022-1317
ER  - 

TY  - JOUR
AB  - Hepatitis B virus (HBV) is one of the world's major unconquered infections, resulting in progressive liver disease and current treatments rarely cure infection. A major limitation to discovering new therapies is our limited knowledge of HBV entry and dissemination pathways that hinders the development of in vitro culture systems. To address this gap in our understanding we optimised the genesis of infectious lentiviral pseudoparticles (HBVpp). The recent discovery that the bile salt transporter NTCP acts as a receptor for HBV enabled us to assess the receptor dependency of HBVpp infection. HBVpp preferentially infect hepatoma cells expressing NTCP, whereas other non-liver cells engineered to express NTCP do not support infection, suggesting that additional hepatocyte-specific factors are required for HBVpp internalisation. These results highlight the value of the HBVpp system to dissect the pathways of HBV entry and dissemination.
AU  - Meredith, L.W.*
AU  - Hu, K.*
AU  - Cheng, X.
AU  - Howard, C.R.*
AU  - Baumert, T.F.*
AU  - Balfe, P.*
AU  - van de Graaf, K.F.*
AU  - Protzer, U.
AU  - McKeating, J.A.
C1  - 47244
C2  - 39292
CY  - Reading
SP  - 121-127
TI  - Lentiviral hepatitis B pseudotype entry requires NTCP and additional hepatocyte-specific factors.
JO  - J. Gen. Virol.
VL  - 97
PB  - Soc General Microbiology
PY  - 2016
SN  - 0022-1317
ER  - 

TY  - JOUR
AB  - Newcastle disease virus (NDV) causes a severe and economically significant disease affecting almost the entire poultry industry worldwide. However, factors that affect NDV replication in host cells are poorly understood. Raf kinase inhibitory protein (RKIP) is a physiological inhibitor of c-RAF kinase and NF-kB signalling, known for their functions in the control of immune response as well as tumour invasion and metastasis. In the present study, we investigated the consequences of overexpression of host RKIP during viral infection. We demonstrate that NDV infection represses RKIP expression thereby promoting virus replication. Experimental upregulation of RKIP in turn acts as a potential antiviral defence mechanism in host cells that restricts NDV replication by repressing the activation of Raf/MEK/ERK and IkBα/NF-kB signalling pathways. Our results not only extend the concept of linking NDV–host interactions, but also reveal RKIP as a new class of protein-kinase-inhibitor protein that affects NDV replication with therapeutic potential.
AU  - Yin, R.*
AU  - Liu, X.*
AU  - Bi, Y.*
AU  - Xie, G.*
AU  - Zhang, P.*
AU  - Meng, X.*
AU  - Ai, L.*
AU  - Xu, R.*
AU  - Sun, Y.*
AU  - Stöger, T.
AU  - Ding, Z.*
C1  - 46819
C2  - 37871
SP  - 2579-2586
TI  - Expression of raf kinase inhibitor protein is down regulated in response to newcastle disease virus infection to promote viral replication.
JO  - J. Gen. Virol.
VL  - 96
IS  - 9
PY  - 2015
SN  - 0022-1317
ER  - 

TY  - JOUR
AB  - Human cytomegalovirus (HCMV) interferes with MHC class I-restricted antigen presentation and thereby reduces recognition by CD8+ T cells. This interference is primarily mediated by ER-resident glycoproteins that are encoded in the US2-11 region of the viral genome. Such a suppression of recognition would be of particular importance immediately after infection, because several immunodominant viral antigens are already present in the cell in this phase. However, it is not known which of the evasion proteins gpUS2-11 interfere with antigen presentation to CD8+ T cells at this time of infection. Here we address this question, using recombinant viruses (RV) that express only one of the immunoevasins gpUS2, gpUS3, or gpUS11. Infection with RV-US3 had only a limited impact on the presentation of peptides from the CD8+ T cell antigens IE1 and pp65 under immediate-early conditions imposed by cycloheximide-actinomycin D blocking. Unexpectedly, both RV-US2 and RV-US11 considerably impaired the recognition of IE1 and pp65 by CD8+ T cells, and both US2 and, to lesser extent, US11 were transcribed under IE conditions. Thus, gpUS2 and gpUS11 are key effectors of MHC class I immune evasion immediately after HCMV infection.
AU  - Hesse, J.*
AU  - Ameres, S.
AU  - Besold, K.*
AU  - Krauter, S.*
AU  - Moosmann, A.
AU  - Plachter, B.*
C1  - 11602
C2  - 30710
SP  - 376-386
TI  - Suppression of CD8+ T cell recognition in the immediate-early phase of human cytomegalovirus infection.
JO  - J. Gen. Virol.
VL  - 94
IS  - 2
PB  - Soc. of General Microbiology
PY  - 2013
SN  - 0022-1317
ER  - 

TY  - JOUR
AB  - Although ORF23 is conserved among gammaherpesviruses, its role during infection is unknown. Here, we studied the expression of ORF23 of murine gammaherpesvirus 68 (MHV-68) and its role during infection. ORF23 mRNA was detected in infected cells as a late transcript. The ORF23 protein product could be expressed and detected as an N-terminally FLAG-tagged protein by Western blot and indirect immunofluorescence. To investigate the role of ORF23 in the infection cycle of a gammaherpesvirus, we constructed an ORF23 deletion mutant of MHV-68. The analysis of the ORF23 deletion mutant suggested that ORF23 of MHV-68 is neither essential for replication in cell culture nor for lytic or latent infection in vivo. A phenotype of the ORF23 deletion mutant, reflected by a moderate reduction in lytic replication and latency amplification, was only detectable in the face of direct competition to the parental virus.
AU  - Ohno, S.
AU  - Steer, B.
AU  - Sattler, C.
AU  - Adler, H.
C1  - 7518
C2  - 29777
SP  - 1076-1080
TI  - ORF23 of murine gammaherpesvirus 68 is non-essential for in vitro and in vivo infection.
JO  - J. Gen. Virol.
VL  - 93
IS  - Part 5
PB  - Society For General Microbiology
PY  - 2012
SN  - 0022-1317
ER  - 

TY  - JOUR
AB  - The human genome comprises approximately 8-9 % of human endogenous retroviruses (HERVs) that are transcribed with tissue specificity. However, relatively few organs have been examined in detail for individual differences in HERV transcription pattern, nor have tissue-to-cell culture comparisons been frequently performed. Using an HERV-specific DNA microarray, a core HERV transcription profile was established for the human kidney comparing 10 tissue samples. This core represents HERV groups expressed uniformly or nearly so in non-tumour kidney tissue. The profiles obtained from non-tumour tissues were compared to 10 renal tumour tissues (renal cell carcinoma, RCC) derived from the same individuals and additionally, to 22 RCC cell lines. No RCC cell line or tumour-specific differences were observed, suggesting that HERV transcription is not altered in RCC. However, when comparing tissue transcription to cell line transcription, there were consistent differences. The differences were irrespective of cancer state and included cell lines derived from non-tumour kidney tissue, suggesting that a specific alteration of HERV transcription occurs when establishing cell lines. In contrast to previous publications, all known HERV-derived tumour antigens, including those identified in RCC, were expressed both in multiple RCC cell lines and several non-tumour tissue-derived cell lines, a result that contrasts with findings from patient samples. The results establish the core kidney transcription pattern of HERVs and reveal differences between cell culture lines and tissue samples.
AU  - Haupt, S.
AU  - Tisdale, M.*
AU  - Vincendeau, M.
AU  - Clements, M.A.*
AU  - Gauthier, D.T.*
AU  - Lance, R.*
AU  - Semmes, O.J.*
AU  - Turqueti-Neves, A.
AU  - Nößner, E.
AU  - Leib-Mösch, C.
AU  - Greenwood, A.D.*
C1  - 6566
C2  - 28877
SP  - 2356-2366
TI  - Human endogenous retrovirus transcription profiles of the kidney and kidney-derived cell lines.
JO  - J. Gen. Virol.
VL  - 92
IS  - 10
PB  - SGM
PY  - 2011
SN  - 0022-1317
ER  - 

TY  - JOUR
AB  - Hepatitis C virus (HCV) infection is prevalent throughout the world and interferon (IFN)-based treatments are currently the only therapeutic option. However, depending upon variations in their human leukocyte antigen (HLA), some patients do not respond well to IFN therapy. The current study evaluated the HLA allele and haplotype distribution of 204 HCV-seropositive individuals from Islamabad, Pakistan, who were receiving standard IFN therapy. In this cohort, 150 patients (74%) showed a sustained virological response to IFN therapy, whereas 54 (26%) did not. In addition to the HCV patients, 102 unrelated healthy volunteers were used as controls. DNA was isolated from the blood of the patients and controls for HLA-DRB1 and HLA-DQB1 allele typing, whilst plasma was used for HCV detection and genotyping. HLA-DRB1*04 was found to impart a significant protective advantage [Bonferroni-corrected P value (pc)=0.047] against HCV infection. In patients on IFN therapy, HLA-DRB1*11 and -DQB1*0301 (pc=0.044) were found to be associated with viral clearance. In contrast, HLA-DRB1*07 (pc=0.008) individually or in combination with HLA-DQB1*02 was found to be associated with viral persistence. These associations of HLA with HCV persistence or clearance will be beneficial in deciding the therapeutic regimen for Pakistani patients infected with HCV genotype 3a.
AU  - Ali, L.*
AU  - Mansoor, A.*
AU  - Ahmad, N.
AU  - Siddiqi, S.*
AU  - Mazhar, K.*
AU  - Muazzam, A.G.*
AU  - Qamar, R.*
AU  - Khan, K.M.*
C1  - 2317
C2  - 27520
SP  - 1931-1938
TI  - Patient HLA-DRB1* and -DQB1* allele and haplotype association with hepatitis C virus persistence and clearance.
JO  - J. Gen. Virol.
VL  - 91
IS  - 8
PB  - Society General Microbiology
PY  - 2010
SN  - 0022-1317
ER  - 

TY  - JOUR
AB  - Vaccinia virus (VACV) infection induces phosphorylation of eukaryotic translation initiation factor 2{alpha} (eIF2{alpha}), which inhibits cellular and viral protein synthesis. In turn, VACV evolved the capacity to antagonise this anti-viral response by expressing the viral host range proteins K3 and E3. Here, we reveal that the host range genes K1L and C7L also prevent eIF2{alpha} phosphorylation in modified VACV Ankara (MVA) infection of several human and murine cell lines. Moreover, C7L-deleted MVA (MVA-{Delta}C7L) lacked late gene expression, which could be rescued by the function of either host range factor K1 or C7. We demonstrate that viral gene expression was blocked after viral DNA replication, and that it was independent of apoptosis induction. Furthermore, we found that eIF2{alpha} phosphorylation in MVA-{Delta}C7L infected cells is mediated by protein kinase R (PKR) as shown in murine embryonic fibroblasts (MEF) lacking PKR function, and demonstrated that this is not due to reduced E3L gene expression. The block of eIF2{alpha} phosphorylation by C7 could be complemented by K1 in cells infected with MVA-{Delta}C7L encoding a re-inserted K1L gene (MVA-{Delta}C7L-K1L). Importantly, our data illustrate that eIF2{alpha} phosphorylation by PKR is not responsible for the block of late viral gene expression. This suggests that other mechanisms targeted by C7 and K1 are essential for completing the MVA gene expression cycle and likely also for VACV replication in a diverse set of cell types.
AU  - Backes, S.*
AU  - Sperling, K.M.*
AU  - Zwilling, J.*
AU  - Gasteiger, G.*
AU  - Ludwig, H.*
AU  - Kremmer, E.
AU  - Schwantes, A.*
AU  - Staib, C.*
AU  - Sutter, G.*
C1  - 700
C2  - 26732
SP  - 470-482
TI  - Viral host-range factor C7 or K1 is essential for modified vaccinia virus Ankara late gene expression in human and murine cells, irrespective of their capacity to inhibit protein kinase R-mediated phosphorylation of eukaryotic translation initiation factor 2α.
JO  - J. Gen. Virol.
VL  - 91
IS  - 2
PY  - 2010
SN  - 0022-1317
ER  - 

TY  - JOUR
AB  - At the cellular level, cells infected with human immunodeficiency virus type 1 (HIV-1) exhibit immunity to a second infection by the virus that initiated the first infection or by related viruses [superinfection resistance (SIR)]. In the case of HIV infection, SIR was basically attributed to downregulation of the CD4 receptors. We have recently reported on an interaction between HIV-1 Rev and integrase (IN) proteins, which results in inhibition of IN activity in vitro and integration of cDNA in HIV-1-infected cells. A novel function for the viral Rev protein in controlling integration of HIV cDNAs was thus proposed. The results of the present work suggest involvement of the inhibitory Rev in sustaining SIR. A single exposure to wild-type HIV-1 resulted in one to two integrations per cell. The number of integrated proviral cDNA copies remained at this low level even after double infection or superinfection. SIR was dependent on Rev expression by the strain used for the first infection and was eliminated by peptides that disrupt intracellular complex formation between IN and Rev. The same lack of resistance was observed in the absence of Rev, namely following first infection with a DeltaRev HIV strain. The involvement of Rev, expressed from either unintegrated or integrated viral cDNA, in promoting SIR was clearly demonstrated. We conclude that SIR involves Rev-dependent control of HIV cDNA integration.
AU  - Levin, A.*
AU  - Hayouka, Z.*
AU  - Friedler, A.*
AU  - Brack-Werner, R.
AU  - Volsky, D.J.*
AU  - Loyter, A.*
C1  - 5314
C2  - 27631
SP  - 1503-1513
TI  - A novel role for the viral Rev protein in promoting resistance to superinfection by human immunodeficiency virus type 1.
JO  - J. Gen. Virol.
VL  - 91
IS  - 6
PB  - SGM
PY  - 2010
SN  - 0022-1317
ER  - 

TY  - JOUR
AB  - In cells infected with Kaposi's sarcoma-associated herpesvirus (KSHV), the activation of mitogen-activated protein kinase (MAPK) pathways plays a crucial role early after virus infection as well as during reactivation. In order to systematically identify viral proteins activating MAPK pathways in KSHV-infected cells, a clone collection of KSHV open reading frames (ORFs) was screened for induction of the serum response element (SRE), as SRE is induced by MAPKs. The strongest induction of the SRE was found with ORF73 (latency-associated nuclear antigen 1, or Lana-1), although weaker activation was also found with the kaposin B isoform, ORF54 (dUTPase) and ORF74 (G-protein-coupled receptor). The bipartite SRE is bound by a ternary complex consisting of serum response factor (SRF) and ternary complex factor. Lana-1 bound directly to SRF, but also to the MED25 (ARC92/ACID-1), MED15 (PCQAP) and MED23 (Sur-2) subunits of the Mediator complex, a multi-subunit transcriptional co-activator complex for RNA polymerase II. Lana-1-induced SRE activation was inhibited by the dominant-negative N-terminal domain of the MED25 mediator subunit, suggesting that this subunit mediates Lana-1-induced SRE activation. In summary, these data suggest a model in which Lana-1 acts as an adaptor between the transcription factor SRF and the basal transcriptional machinery.
AU  - Roupelieva, M.*
AU  - Griffiths, S.J.*
AU  - Kremmer, E.
AU  - Meisterernst, M.
AU  - Viejo-Borbolla, A.*
AU  - Schulz, T.*
AU  - Haas, J.*
C1  - 5921
C2  - 27493
SP  - 1138-1149
TI  - Kaposi's sarcoma-associated herpesvirus Lana-1 is a major activator of the serum response element and mitogen-activated protein kinase pathways via interactions with the Mediator complex.
JO  - J. Gen. Virol.
VL  - 91
IS  - 5
PB  - Society General Microbiology
PY  - 2010
SN  - 0022-1317
ER  - 

TY  - JOUR
AB  - The Epstein-Barr virus (EBV) nuclear antigen 2 (EBNA2) gene product is the key regulator of the latent genes of EBV and essential for EBV-mediated transformation of human primary B cells. Viral mutants were constructed carrying a deletion of the EBNA2 conserved region 4 (CR4). Primary resting B cells infected with the DeltaCR4-EBNA2 mutant virus were dramatically impaired for B cell transformation. Lymphoblastoid cell lines (LCLs) established with this mutant EBV revealed a prolonged population doubling time when cells were cultivated at low cell densities, which are not critical for wild-type-infected cells. Low-level spontaneous cell death occurred when the cells were cultivated at suboptimal cell densities. The phenotype of B cells and LCLs infected with the DeltaCR4-EBNA2 mutant virus indicated that the CR4 region of EBNA2 specifically contributes to the viability of the cells rather than affecting cell division rates.
AU  - Grabusic, K.
AU  - Maier, S.
AU  - Hartmann, A.
AU  - Mantik, A.
AU  - Hammerschmidt, W.
AU  - Kempkes, B.
C1  - 4462
C2  - 23997
SP  - 3169-3176
TI  - The CR4 region of EBNA2 convers viability of Epstein-Barr virus-transformed B cells by CBF1-independent signalling.
JO  - J. Gen. Virol.
VL  - 87
IS  - 11
PY  - 2006
SN  - 0022-1317
ER  - 

TY  - JOUR
AU  - Staib, C.
AU  - Suezer, Y.*
AU  - Kisling, S.
AU  - Kalinke, U.*
AU  - Sutter, G.*
C1  - 4219
C2  - 23902
SP  - 2917-2921
TI  - Short-term, but not post-exposure, protection against lethal orthopoxvirus challenge after immunization with modified vaccinia virus Ankara.
JO  - J. Gen. Virol.
VL  - 87
PY  - 2006
SN  - 0022-1317
ER  - 

TY  - JOUR
AU  - Schaadt, E.
AU  - Baier, B.
AU  - Mautner, J.
AU  - Bornkamm, G.W.
AU  - Adler, B.*
C1  - 398
C2  - 22560
SP  - 551-559
TI  - Epstein-Barr virus latent membrane protein 2A mimics B-cell receptor-dependent virus reactivation.
JO  - J. Gen. Virol.
VL  - 86
PY  - 2005
SN  - 0022-1317
ER  - 

TY  - JOUR
AU  - Staib, C.
AU  - Kisling, S.
AU  - Erfle, V.
AU  - Sutter, G.
C1  - 1993
C2  - 22810
SP  - 1997-2006
TI  - Inactivation of the viral interleukin 1ß receptor improves CD8+ T-cell memory responses elicited upon immunization with modified vaccinia virus Ankara.
JO  - J. Gen. Virol.
VL  - 86
PY  - 2005
SN  - 0022-1317
ER  - 

TY  - JOUR
AU  - Koopman, G.*
AU  - Mortier, D.*
AU  - Hofmann, S.M.*
AU  - Niphuis, H.*
AU  - Fagrouch, Z.*
AU  - Norley, S.*
AU  - Sutter, G.
AU  - Liljeström, P.*
AU  - Heeney, J.L.*
C1  - 3044
C2  - 22424
SP  - 2915-2924
TI  - Vaccine protection from CD4⁺ T-cell loss caused by simian immunodeficiency virus (SIV) mac251 is afforded by sequential immunization with three unrelated vaccine vectors encoding multiple SIV antigens.
JO  - J. Gen. Virol.
VL  - 85
PY  - 2004
SN  - 0022-1317
ER  - 

TY  - JOUR
AU  - Mäkitalo, B.*
AU  - Sutter, G.
AU  - Erfle, V.
C1  - 3047
C2  - 22427
SP  - 2407-2419
TI  - Enhanced cellular immunity and systemic control of SHIV infection by combined parenteral and mucosal administration of a DNA prime MVA boost vaccine regimen.
JO  - J. Gen. Virol.
VL  - 85
PY  - 2004
SN  - 0022-1317
ER  - 

TY  - JOUR
AU  - Nimmerjahn, F.
AU  - Dudziak, D.
AU  - Dirmeier, U.
AU  - Hobom, G.*
AU  - Riedel, A.*
AU  - Schlee, M.
AU  - Staudt, L.M.*
AU  - Rosenwald, A.*
AU  - Behrends, U.*
AU  - Bornkamm, G.W.
AU  - Mautner, J.*
C1  - 2111
C2  - 22033
SP  - 2347-2356
TI  - Active NF-kB signalling is a prerequisite for influenza virus infection.
JO  - J. Gen. Virol.
VL  - 85
PY  - 2004
SN  - 0022-1317
ER  - 

TY  - JOUR
AU  - Simas, J.P.*
AU  - Marques, S.*
AU  - Bridgeman, A.*
AU  - Efstathiou, S.*
AU  - Adler, H.
C1  - 4387
C2  - 21983
SP  - 2789-2797
TI  - The M2 gene product of murine gammaherpesvirus 68 is required for efficient colonization of splenic follicles but is not necessary for expansion of latently infected germinal centre B cells.
JO  - J. Gen. Virol.
VL  - 85
PY  - 2004
SN  - 0022-1317
ER  - 

TY  - JOUR
AU  - Meiser, A.
AU  - Boulanger, D.
AU  - Sutter, G.
AU  - Krijnse Locker, J.*
C1  - 22257
C2  - 21024
SP  - 1383-1392
TI  - Comparison of virus production in chicken embryo fibroblasts infected with the WR, IHD-J and  MVA strains of vaccinia virus : IHD-J is most efficient in trans-Golgi network wrapping and extracellular eveloped virus release.
JO  - J. Gen. Virol.
VL  - 84
PY  - 2003
SN  - 0022-1317
ER  - 

TY  - JOUR
AU  - Nilsson, C.*
AU  - Sutter, G.
AU  - Jallow-Walther, L.*
AU  - Ten Haaft, P.*
AU  - Akerblom, L.*
AU  - Heeney, J.*
AU  - Erfle, V.
AU  - Böttiger, P.*
AU  - Biberfeld, G.*
AU  - Thorstensson, R.*
C1  - 22255
C2  - 21021
SP  - 807-818
TI  - Immunization with recombinant modified vaccinia virus Ankara can modify mucosal simian  immunodeficiency virus infection and delay disease progression in macaques.
JO  - J. Gen. Virol.
VL  - 83
PY  - 2002
SN  - 0022-1317
ER  - 

TY  - JOUR
AB  - Antimicrobial peptides are effectors of innate immunity, providing their hosts with rapid non-specific defence against parasitic invaders. In this report, the effects are assessed of two well-characterized antimicrobial amphipathic peptides (melittin and cecropin) on human immunodeficiency virus 1 (HIV-1) replication and gene expression in acutely infected cells at subtoxic concentrations. Production of infectious, cell-free virus was inhibited in a dose-dependent manner, with ID50 values in the range 0.9-1.5 microM for melittin and 2-3 microM for cecropin. Analysis of the effect of melittin on cell-associated virus production revealed decreased levels of Gag antigen and HIV-1 mRNAs. Transient transfection assays with HIV long terminal repeat (LTR)-driven reporter gene plasmids indicated that melittin has a direct suppressive effect on activity of the HIV LTR. HIV LTR activity was also reduced in human cells stably transfected with retroviral expression plasmids for the melittin or cecropin gene. It is concluded that antimicrobial peptides such as melittin and cecropin are capable of inhibiting cell-associated production of HIV-1 by suppressing HIV-1 gene expression.
AU  - Wachinger, M.
AU  - Kleinschmidt, A.*
AU  - Winder, D.*
AU  - von Pechmann, N.
AU  - Ludvigsen, A.
AU  - Neumann, M.
AU  - Holle, R.
AU  - Salmons, B.*
AU  - Erfle, V.
AU  - Brack-Werner, R.
C1  - 24167
C2  - 31450
SP  - 731-740
TI  - Antimicrobial peptides melittin and cecropin inhibit replication of human immunodeficiency virus 1 by suppressing viral gene expression.
JO  - J. Gen. Virol.
VL  - 79
IS  - 4
PB  - Soc. General Microbiology
PY  - 1998
SN  - 0022-1317
ER  - 

TY  - JOUR
AU  - Brielmeier, M.
AU  - Mautner, J.
AU  - Laux, G.
AU  - Hammerschmidt, W.
C1  - 10080
C2  - 22864
SP  - 2807-2818
TI  - The latent membrane protein 2 gene of Epstein-Barr virus is important for efficient B cell immortalization.
JO  - J. Gen. Virol.
VL  - 77
PY  - 1996
SN  - 0022-1317
ER  - 

TY  - JOUR
AU  - Faff, O.
AU  - Murray, A.B.
AU  - Schmidt, J.
AU  - Leib-Mösch, C.
AU  - Erfle, V.
AU  - Hehlmann, R.
C1  - 20069
C2  - 13243
SP  - 1087-1097
TI  - Retrovirus-like Particles from the hum T47D Cell Line are Related to Mouse Mmary Tumour Virus and are of Human Endogenous Origin.
JO  - J. Gen. Virol.
VL  - 73
PY  - 1992
SN  - 0022-1317
ER  - 

TY  - JOUR
AU  - Kirchner, E.A.
AU  - Bornkamm, G.W.
AU  - Polack, A.
C1  - 18717
C2  - 11821
SP  - 2391-2398
TI  - Transcriptional Acitvity Across the Epstein-Barr Virus Genome in Raji Cells During Latency and After Induction of an Abortive Lytic Cycle.
JO  - J. Gen. Virol.
VL  - 72
PY  - 1991
SN  - 0022-1317
ER  - 

TY  - JOUR
AB  - The intact terminal protein genes (TP1 and TP2) of Epstein-Barr virus (EBV) are created upon infection by circularization of the linear viral genome at its terminal repeats. The structure of the 1 7 kb TP2 latent mRNA has been determined by cDNA analysis and Northern blotting, revealing its close relation to TP1 MRNA. The  1 7 kb transcript is expressed from a different promoter and has a different 5´exon from TP1 but is also spliced across the terminal repeats. The last eight exons are common to the TP1 and TP2 RNAs. The TP2 promoter is 3 3 kb downstream of the TP1 promoter and  is part of a bidirectional latent EBV promoter region transcribing the TP2 and the latent membrane protein RNAs in opposite directions.
AU  - Laux, G.
AU  - Economou, A.
AU  - Farrell, P.J.
C1  - 19275
C2  - 12348
SP  - 3079-3084
TI  - The Terminal Protein Gene 2 of Epstein-Barr Virus Is Transcribed from a Bidirectional Latent Promoter Region.
JO  - J. Gen. Virol.
VL  - 70
PY  - 1989
SN  - 0022-1317
ER  - 

TY  - JOUR
AB  - The double-stranded (ds)DNAs of the three closely related temperate Pseudomonas pseudoflava bacteriophages gd, ge and gf were studied biochemically and biophysically. The GC content of the DNA was 67.4 ± 0.5% and differed only slightly from that of the host P. pseudoflava. By electron microscopic length measurements a mol. wt. of 26.1 x 106 to 26.7 x 106 was calculated for the three bacteriophage DNAs. Homogeneity of the bacteriophage DNAs was further demonstrated by specific cleavage with restriction endonucleases EcoRI and HindIII. It was concluded that the three homo-immune bacteriophages are identical. The genome size of the host P. pseudoflava GA3 was 3.7 x 109 as calculated from optical renaturation rate measurements with Xanthomonas pelargonii reference DNA. The bacteriophage gd genome thus amounts to 0.7% of the chromosome of this bacterial host.
AU  - Auling, G.
AU  - Bernard, U.
AU  - Huettermann, A.
AU  - Mayer, F.C.
C1  - 40932
C2  - 38311
SP  - 51-59
TI  - Characterization and comparison of the DNAs of the three closely related bacteriophages gd, ge and gf with the genome DNA of the hydrogen-oxidizing host strain Pseudomonas pseudoflava GA3.
JO  - J. Gen. Virol.
VL  - 49
IS  - 1
PY  - 1980
SN  - 0022-1317
ER  -