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  1. Article ; Online: Establishment of Recombinant Trisegmented Mopeia Virus Expressing Two Reporter Genes for Screening of Mammarenavirus Inhibitors.

    Oestereich, Lisa / Wurr, Stephanie / Becker-Ziaja, Beate / Bockholt, Sabrina / Pahlmann, Meike / Cadar, Daniel / Kümmerer, Beate M / Günther, Stephan / Kerber, Romy

    Viruses

    2022  Volume 14, Issue 9

    Abstract: Highly pathogenic Arenaviruses, like the Lassa Virus (LASV), pose a serious public health threat in affected countries. Research and development of vaccines and therapeutics are urgently needed but hampered by the necessity to handle these pathogens ... ...

    Abstract Highly pathogenic Arenaviruses, like the Lassa Virus (LASV), pose a serious public health threat in affected countries. Research and development of vaccines and therapeutics are urgently needed but hampered by the necessity to handle these pathogens under biosafety level 4 conditions. These containment restrictions make large-scale screens of antiviral compounds difficult. Therefore, the Mopeia virus (MOPV), closely related to LASV, is often used as an apathogenic surrogate virus. We established for the first time trisegmented MOPVs (r3MOPV) with duplicated S segments, in which one of the viral genes was replaced by the reporter genes ZsGreen (ZsG) or Renilla Luciferase (Rluc), respectively. In vitro characterization of the two trisegmented viruses (r3MOPV ZsG/Rluc and r3MOPV Rluc/ZsG), showed comparable growth behavior to the wild type virus and the expression of the reporter genes correlated well with viral titer. We used the reporter viruses in a proof-of-principle in vitro study to evaluate the antiviral activity of two well characterized drugs. IC
    MeSH term(s) Antiviral Agents/pharmacology ; Arenaviridae/genetics ; Genes, Reporter ; Lassa virus ; Luciferases, Renilla/genetics ; Orthopoxvirus/genetics ; Research
    Chemical Substances Antiviral Agents ; Luciferases, Renilla (EC 1.13.12.5)
    Language English
    Publishing date 2022-08-25
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2516098-9
    ISSN 1999-4915 ; 1999-4915
    ISSN (online) 1999-4915
    ISSN 1999-4915
    DOI 10.3390/v14091869
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Establishment of Recombinant Trisegmented Mopeia Virus Expressing Two Reporter Genes for Screening of Mammarenavirus Inhibitors

    Oestereich, Lisa / Wurr, Stephanie / Becker-Ziaja, Beate / Bockholt, Sabrina / Pahlmann, Meike / Cadar, Daniel / Kümmerer, Beate M. / Günther, Stephan / Kerber, Romy

    Viruses. 2022 Aug. 25, v. 14, no. 9

    2022  

    Abstract: Highly pathogenic Arenaviruses, like the Lassa Virus (LASV), pose a serious public health threat in affected countries. Research and development of vaccines and therapeutics are urgently needed but hampered by the necessity to handle these pathogens ... ...

    Abstract Highly pathogenic Arenaviruses, like the Lassa Virus (LASV), pose a serious public health threat in affected countries. Research and development of vaccines and therapeutics are urgently needed but hampered by the necessity to handle these pathogens under biosafety level 4 conditions. These containment restrictions make large-scale screens of antiviral compounds difficult. Therefore, the Mopeia virus (MOPV), closely related to LASV, is often used as an apathogenic surrogate virus. We established for the first time trisegmented MOPVs (r3MOPV) with duplicated S segments, in which one of the viral genes was replaced by the reporter genes ZsGreen (ZsG) or Renilla Luciferase (Rluc), respectively. In vitro characterization of the two trisegmented viruses (r3MOPV ZsG/Rluc and r3MOPV Rluc/ZsG), showed comparable growth behavior to the wild type virus and the expression of the reporter genes correlated well with viral titer. We used the reporter viruses in a proof-of-principle in vitro study to evaluate the antiviral activity of two well characterized drugs. IC₅₀ values obtained by Rluc measurement were similar to those obtained by virus titers. ZsG expression was also suitable to evaluate antiviral effects. The trisegmented MOPVs described here provide a versatile and valuable basis for rapid high throughput screening of broadly reactive antiviral compounds against arenaviruses under BSL-2 conditions.
    Keywords Lassa mammarenavirus ; Renilla ; antiviral properties ; biosafety ; luciferase ; public health ; research and development ; therapeutics ; viral load ; viruses
    Language English
    Dates of publication 2022-0825
    Publishing place Multidisciplinary Digital Publishing Institute
    Document type Article
    ZDB-ID 2516098-9
    ISSN 1999-4915
    ISSN 1999-4915
    DOI 10.3390/v14091869
    Database NAL-Catalogue (AGRICOLA)

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  3. Article ; Online: Circulation of Lassa virus across the endemic Edo-Ondo axis, Nigeria, with cross-species transmission between multimammate mice.

    Adesina, Adetunji Samuel / Oyeyiola, Akinlabi / Obadare, Adeoba / Igbokwe, Joseph / Abejegah, Chukwuyem / Akhilomen, Patience / Bangura, Umaru / Asogun, Danny / Tobin, Ekaete / Ayodeji, Olufemi / Osoniyi, Omolaja / Davis, Chris / Thomson, Emma C / Pahlmann, Meike / Günther, Stephan / Fichet-Calvet, Elisabeth / Olayemi, Ayodeji

    Emerging microbes & infections

    2023  Volume 12, Issue 1, Page(s) 2219350

    Abstract: We phylogenetically compared sequences of the zoonotic Lassa virus (LASV) obtained ... ...

    Abstract We phylogenetically compared sequences of the zoonotic Lassa virus (LASV) obtained from
    MeSH term(s) Humans ; Mice ; Animals ; Lassa virus/genetics ; Nigeria/epidemiology ; Phylogeny ; Lassa Fever/epidemiology ; Lassa Fever/veterinary ; Murinae
    Language English
    Publishing date 2023-06-08
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2681359-2
    ISSN 2222-1751 ; 2222-1751
    ISSN (online) 2222-1751
    ISSN 2222-1751
    DOI 10.1080/22221751.2023.2219350
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Focussed Assessment with Sonography in acute Lassa Fever (FASLa): Development of a point-of-care protocol and description of common ultrasound findings.

    Erameh, Cyril O / Koch, Till / Edeawe, Osahogie Isaac / Oestereich, Lisa / Omansen, Till / Jochum, Johannes / Adomeh, Donatus I / Ikponmwonsa, Odia / Aire, Chris / Pahlmann, Meike / Asogun, Danny A / Ogbaini-Emovon, Ephraim / Okogbenin, Sylvanus A / Günther, Stephan / Ramharter, Michael / Akideno, Peter E / Kreuels, Benno

    The Journal of infection

    2023  Volume 87, Issue 1, Page(s) 27–33

    Abstract: Background: Managing Lassa fever (LF) patients is challenging because of the complexity of this life-threatening infectious disease, the necessary isolation measures, and the limited resources in countries where it is endemic. Point-of-care ... ...

    Abstract Background: Managing Lassa fever (LF) patients is challenging because of the complexity of this life-threatening infectious disease, the necessary isolation measures, and the limited resources in countries where it is endemic. Point-of-care ultrasonography (POCUS) is a promising low-cost imaging technique that may help in guiding the management of patients.
    Methods: We conducted this observational study at the Irrua Specialist Teaching Hospital in Nigeria. We developed a POCUS protocol, trained local physicians who applied the protocol to LF patients and recorded and interpreted the clips. These were then independently re-evaluated by an external expert, and associations with clinical, laboratory and virological data were analyzed.
    Findings: We developed the POCUS protocol based on existing literature and expert opinion and trained two clinicians, who then used POCUS to examine 46 patients. We observed at least one pathological finding in 29 (63%) patients. Ascites was found in 14 (30%), pericardial effusion in 10 (22%), pleural effusion in 5 (11%), and polyserositis in 7 (15%) patients, respectively. Eight patients (17%) showed hyperechoic kidneys. Seven patients succumbed to the disease while 39 patients survived, resulting in a fatality rate of 15%. Pleural effusions and hyper-echoic kidneys were associated with increased mortality.
    Interpretation: In acute LF, a newly established POCUS protocol readily identified a high prevalence of clinically relevant pathological findings. The assessment by POCUS required minimal resources and training; the detected pathologies such as pleural effusions and kidney injury may help to guide the clinical management of the most at-risk LF patients.
    MeSH term(s) Humans ; Lassa Fever/diagnostic imaging ; Physicians ; Pleural Effusion ; Point-of-Care Systems ; Ultrasonography/methods
    Language English
    Publishing date 2023-04-17
    Publishing country England
    Document type Journal Article ; Observational Study ; Research Support, Non-U.S. Gov't
    ZDB-ID 424417-5
    ISSN 1532-2742 ; 0163-4453
    ISSN (online) 1532-2742
    ISSN 0163-4453
    DOI 10.1016/j.jinf.2023.04.008
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Fcγ-Receptor-Based Enzyme-Linked Immunosorbent Assays for Sensitive, Specific, and Persistent Detection of Anti-SARS-CoV-2 Nucleocapsid Protein IgG Antibodies in Human Sera.

    Deschermeier, Christina / Ehmen, Christa / von Possel, Ronald / Murawski, Carolin / Rushton, Ben / Amuasi, John / Sarpong, Nimako / Maiga-Ascofaré, Oumou / Rakotozandrindrainy, Raphael / Asogun, Danny / Ighodalo, Yemisi / Oestereich, Lisa / Duraffour, Sophie / Pahlmann, Meike / Emmerich, Petra

    Journal of clinical microbiology

    2022  Volume 60, Issue 6, Page(s) e0007522

    Abstract: Sensitive and specific serological tests are mandatory for epidemiological studies evaluating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) prevalence as well as coronavirus disease 2019 (COVID-19) morbidity and mortality rates. The ... ...

    Abstract Sensitive and specific serological tests are mandatory for epidemiological studies evaluating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) prevalence as well as coronavirus disease 2019 (COVID-19) morbidity and mortality rates. The accuracy of results is challenged by antibody waning after convalescence and by cross-reactivity induced by previous infections with other pathogens. By employing a patented platform technology based on capturing antigen-antibody complexes with a solid-phase-bound Fcγ receptor (FcγR) and truncated nucleocapsid protein as the antigen, two SARS-CoV-2 IgG enzyme-linked immunosorbent assays (ELISAs), featuring different serum and antigen dilutions, were developed. Validation was performed using a serum panel comprising 213 longitudinal samples from 35 COVID-19 patients and a negative-control panel consisting of 790 pre-COVID-19 samples from different regions of the world. While both assays show similar diagnostic sensitivities in the early convalescent phase, ELISA 2 (featuring a higher serum concentration) enables SARS-CoV-2 IgG antibody detection for a significantly longer time postinfection (≥15 months). Correspondingly, analytical sensitivity referenced to indirect immunofluorescence testing (IIFT) is significantly higher for ELISA 2 in samples with a titer of ≤1:640; for high-titer samples, a prozone effect is observed for ELISA 2. The specificities of both ELISAs were excellent not only for pre-COVID-19 serum samples from Europe, Asia, and South America but also for several challenging African sample panels. The SARS-CoV-2 IgG FcγR ELISAs, methodically combining antigen-antibody binding in solution and isotype-specific detection of immune complexes, are valuable tools for seroprevalence studies requiring the (long-term) detection of anti-SARS-CoV-2 IgG antibodies in populations with a challenging immunological background and/or in which spike-protein-based vaccine programs have been rolled out.
    MeSH term(s) Antibodies, Viral ; COVID-19/diagnosis ; Enzyme-Linked Immunosorbent Assay/methods ; Humans ; Immunoglobulin G ; Nucleocapsid Proteins ; Receptors, IgG ; SARS-CoV-2 ; Sensitivity and Specificity ; Seroepidemiologic Studies ; Spike Glycoprotein, Coronavirus
    Chemical Substances Antibodies, Viral ; Immunoglobulin G ; Nucleocapsid Proteins ; Receptors, IgG ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2
    Language English
    Publishing date 2022-05-16
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 390499-4
    ISSN 1098-660X ; 0095-1137
    ISSN (online) 1098-660X
    ISSN 0095-1137
    DOI 10.1128/jcm.00075-22
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Rift Valley fever virus minigenome system for investigating the role of L protein residues in viral transcription and replication.

    Jérôme, Hanna / Rudolf, Martin / Lelke, Michaela / Pahlmann, Meike / Busch, Carola / Bockholt, Sabrina / Wurr, Stephanie / Günther, Stephan / Rosenthal, Maria / Kerber, Romy

    The Journal of general virology

    2019  Volume 100, Issue 7, Page(s) 1093–1098

    Abstract: Replicon systems are important tools for investigating viral RNA synthesis. We have developed an ambisense minigenome system for Rift Valley fever virus (RVFV) with the aim to analyse the effects of L gene mutations on viral transcription versus ... ...

    Abstract Replicon systems are important tools for investigating viral RNA synthesis. We have developed an ambisense minigenome system for Rift Valley fever virus (RVFV) with the aim to analyse the effects of L gene mutations on viral transcription versus replication. The overall activity of the replication complex was assessed by expression of a luciferase reporter gene. Northern blot analysis enabled differentiation between synthesis of viral mRNA and replication intermediates. The functionality of the system was demonstrated by probing residues predictably involved in the cap-snatching endonuclease active site in the L protein. Corresponding mutations led to a selective defect in the viral mRNA synthesis as described for other bunyaviruses. The analysis of further L gene mutants revealed an essential role of a C-terminal region in the RVFV L protein in viral transcription. In summary, the established minigenome system is suitable for functional testing of the relevance of residues for viral transcription and replication.
    MeSH term(s) Gene Expression Regulation, Viral ; Genome, Viral ; Mutation ; Rift Valley Fever/virology ; Rift Valley fever virus/genetics ; Rift Valley fever virus/physiology ; Transcription, Genetic ; Viral Proteins/genetics ; Viral Proteins/metabolism ; Virus Replication
    Chemical Substances Viral Proteins
    Language English
    Publishing date 2019-06-06
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 219316-4
    ISSN 1465-2099 ; 0022-1317
    ISSN (online) 1465-2099
    ISSN 0022-1317
    DOI 10.1099/jgv.0.001281
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Tigray Orthohantavirus Infects Two Related Rodent Species Adapted to Different Elevations in Ethiopia.

    Meheretu, Yonas / Stanley, William T / Craig, Evan W / Goüy de Bellocq, Joëlle / Bryja, Josef / Leirs, Herwig / Pahlmann, Meike / Günther, Stephan

    Vector borne and zoonotic diseases (Larchmont, N.Y.)

    2019  Volume 19, Issue 12, Page(s) 950–953

    Abstract: Orthohantaviruses are RNA viruses that some members are known to cause severe zoonotic diseases in humans. Orthohantaviruses are hosted by rodents, soricomorphs (shrews and moles), and bats. Only two orthohantaviruses associated with murid rodents are ... ...

    Abstract Orthohantaviruses are RNA viruses that some members are known to cause severe zoonotic diseases in humans. Orthohantaviruses are hosted by rodents, soricomorphs (shrews and moles), and bats. Only two orthohantaviruses associated with murid rodents are known in Africa, Sangassou orthohantavirus (SANGV) in two species of African wood mice (
    MeSH term(s) Animals ; Ethiopia/epidemiology ; Hantavirus/genetics ; Hantavirus Infections/epidemiology ; Hantavirus Infections/veterinary ; Hantavirus Infections/virology ; Humans ; Phylogeny ; Rodent Diseases/epidemiology ; Rodent Diseases/virology ; Rodentia ; Species Specificity
    Language English
    Publishing date 2019-08-01
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2047199-3
    ISSN 1557-7759 ; 1530-3667
    ISSN (online) 1557-7759
    ISSN 1530-3667
    DOI 10.1089/vbz.2019.2452
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: Tigray Orthohantavirus Infects Two Related Rodent Species Adapted to Different Elevations in Ethiopia

    Meheretu, Yonas / Stanley, William T / Craig, Evan W / Goüy de Bellocq, Joëlle / Bryja, Josef / Leirs, Herwig / Pahlmann, Meike / Günther, Stephan

    Vector borne and zoonotic diseases. 2019 Dec. 01, v. 19, no. 12

    2019  

    Abstract: Orthohantaviruses are RNA viruses that some members are known to cause severe zoonotic diseases in humans. Orthohantaviruses are hosted by rodents, soricomorphs (shrews and moles), and bats. Only two orthohantaviruses associated with murid rodents are ... ...

    Abstract Orthohantaviruses are RNA viruses that some members are known to cause severe zoonotic diseases in humans. Orthohantaviruses are hosted by rodents, soricomorphs (shrews and moles), and bats. Only two orthohantaviruses associated with murid rodents are known in Africa, Sangassou orthohantavirus (SANGV) in two species of African wood mice (Hylomyscus), and Tigray orthohantavirus (TIGV) in the Ethiopian white-footed rat (Stenocephalemys albipes). In this article, we report evidence that, like SANGV, two strains of TIGV occur in two genetically related rodent species, S. albipes and S. sp. A, occupying different elevational zones in the same mountain. Investigating the other members of the genus Stenocephalemys for TIGV could reveal the real diversity of TIGV in the genus.
    Keywords Apodemus ; Chiroptera ; Orthohantavirus ; RNA viruses ; moles ; shrews ; zoonoses ; Ethiopia
    Language English
    Dates of publication 2019-1201
    Size p. 950-953.
    Publishing place Mary Ann Liebert, Inc.
    Document type Article
    ZDB-ID 2047199-3
    ISSN 1557-7759 ; 1530-3667
    ISSN (online) 1557-7759
    ISSN 1530-3667
    DOI 10.1089/vbz.2019.2452
    Database NAL-Catalogue (AGRICOLA)

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  9. Article ; Online: Pharmacokinetics of Ribavirin in the Treatment of Lassa Fever: An Observational Clinical Study at the Irrua Specialist Teaching Hospital, Edo State, Nigeria.

    Groger, Mirjam / Akhideno, Peter / Kleist, Christine J / Babatunde, Femi O / Edeawe, Osahogie / Hinzmann, Julia / Akhigbe, ThankGod / Nwatuzor, Joy / Eifediyi, Gloria / Müller, Jonas / Hinrichs, Mette / Pahlmann, Meike / Sarpong, Francisca Naana / Wagner, Christine / Thielebein, Anke / Aihonwalan, Louis / Koch, Till / Riedner, Maria / Ogbaini-Emovon, Ephraim /
    Okogbenin, Sylvanus / Günther, Stephan / Wicha, Sebastian G / Ramharter, Michael / Oestereich, Lisa / Duraffour, Sophie / Erameh, Cyril

    Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

    2022  Volume 76, Issue 3, Page(s) e841–e848

    Abstract: Background: Lassa fever is endemic in large parts of West Africa. The recommended antiviral treatment is ribavirin. Two treatment regimens are currently endorsed in Nigeria: the "McCormick regimen" based on a study published in 1986 and the "Irrua ... ...

    Abstract Background: Lassa fever is endemic in large parts of West Africa. The recommended antiviral treatment is ribavirin. Two treatment regimens are currently endorsed in Nigeria: the "McCormick regimen" based on a study published in 1986 and the "Irrua regimen" constituting a simplified schedule developed at the Irrua Specialist Teaching Hospital, Nigeria. Evidence for the safety and efficacy of ribavirin in Lassa fever patients is poor and pharmacokinetic data for both regimens are lacking.
    Methods: Polymerase chain reaction-confirmed Lassa fever patients with mild to moderate disease severity were invited to participate in this prospective, observational pharmacokinetic study. Pharmacokinetics of ribavirin, clinical, virologic, and clinical laboratory parameters were assessed.
    Results: Using a population pharmacokinetic approach, plasma concentrations of ribavirin were best described by a 3-compartment model. Drug exposure was remarkably consistent between participants. Overall, drug clearance was 28.5% lower in female compared with male participants. Median (5th-95th percentile) time above half maximal inhibitory concentration (IC50) was 37.3% (16.9%-73.1%), 16.7% (8.2%-58.5%), and 9.6% (4.9%-38.4%) on days 1, 7, and 8, respectively. Clinical laboratory parameters indicated reduction of cell damage and development of hemolytic anemia in the course of the treatment period.
    Conclusions: This observational study characterizes the pharmacokinetics of ribavirin in the treatment of Lassa fever indicating consistent exposure across patients. Whereas only a short time interval of concentrations above the IC50 implies rather low antiviral efficacy in vivo, the prominent reduction of cell damage markers might point to indirect-potentially anti-inflammatory-effects of ribavirin. The role of ribavirin in the treatment of Lassa fever requires further scrutiny.
    MeSH term(s) Humans ; Male ; Female ; Lassa Fever/drug therapy ; Ribavirin/therapeutic use ; Nigeria/epidemiology ; Prospective Studies ; Antiviral Agents/therapeutic use ; Hospitals, Teaching
    Chemical Substances Ribavirin (49717AWG6K) ; Antiviral Agents
    Language English
    Publishing date 2022-09-09
    Publishing country United States
    Document type Observational Study ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1099781-7
    ISSN 1537-6591 ; 1058-4838
    ISSN (online) 1537-6591
    ISSN 1058-4838
    DOI 10.1093/cid/ciac578
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Role of the C terminus of Lassa virus L protein in viral mRNA synthesis.

    Lehmann, Maria / Pahlmann, Meike / Jérôme, Hanna / Busch, Carola / Lelke, Michaela / Günther, Stephan

    Journal of virology

    2014  Volume 88, Issue 15, Page(s) 8713–8717

    Abstract: The N terminus of arenavirus L protein contains an endonuclease presumably involved in "cap snatching." Here, we employed the Lassa virus replicon system to map other L protein sites that might be involved in this mechanism. Residues Phe-1979, Arg-2018, ... ...

    Abstract The N terminus of arenavirus L protein contains an endonuclease presumably involved in "cap snatching." Here, we employed the Lassa virus replicon system to map other L protein sites that might be involved in this mechanism. Residues Phe-1979, Arg-2018, Phe-2071, Asp-2106, Trp-2173, Tyr-2179, Arg-2200, and Arg-2204 were important for viral mRNA synthesis but dispensable for genome replication. Thus, the C terminus of L protein is involved in the mRNA synthesis process, potentially by mediating cap binding.
    MeSH term(s) Cell Line ; Humans ; Lassa virus/genetics ; Lassa virus/physiology ; RNA, Messenger/genetics ; RNA, Viral/genetics ; Viral Proteins/genetics ; Viral Proteins/metabolism ; Virus Replication
    Chemical Substances RNA, Messenger ; RNA, Viral ; Viral Proteins
    Language English
    Publishing date 2014-05-14
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80174-4
    ISSN 1098-5514 ; 0022-538X
    ISSN (online) 1098-5514
    ISSN 0022-538X
    DOI 10.1128/JVI.00652-14
    Database MEDical Literature Analysis and Retrieval System OnLINE

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