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      Current status on the development of pseudoviruses for enveloped viruses

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          Emerging and reemerging infectious diseases have a strong negative impact on public health. However, because many of these pathogens must be handled in biosafety level, 3 or 4 containment laboratories, research and development of antivirals or vaccines against these diseases are often impeded. Alternative approaches to address this issue have been vigorously pursued, particularly the use of pseudoviruses in place of wild‐type viruses. As pseudoviruses have been deprived of certain gene sequences of the virulent virus, they can be handled in biosafety level 2 laboratories. Importantly, the envelopes of these viral particles may have similar conformational structures to those of the wild‐type viruses, making it feasible to conduct mechanistic investigation on viral entry and to evaluate potential neutralizing antibodies. However, a variety of challenging issues remain, including the production of a sufficient pseudovirus yield and the inability to produce an appropriate pseudotype of certain viruses. This review discusses current progress in the development of pseudoviruses and dissects the factors that contribute to low viral yields.

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          Most cited references 105

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          Infectious Hepatitis C Virus Pseudo-particles Containing Functional E1–E2 Envelope Protein Complexes

          The study of hepatitis C virus (HCV), a major cause of chronic liver disease, has been hampered by the lack of a cell culture system supporting its replication. Here, we have successfully generated infectious pseudo-particles that were assembled by displaying unmodified and functional HCV glycoproteins onto retroviral and lentiviral core particles. The presence of a green fluorescent protein marker gene packaged within these HCV pseudo-particles allowed reliable and fast determination of infectivity mediated by the HCV glycoproteins. Primary hepatocytes as well as hepato-carcinoma cells were found to be the major targets of infection in vitro. High infectivity of the pseudo-particles required both E1 and E2 HCV glycoproteins, and was neutralized by sera from HCV-infected patients and by some anti-E2 monoclonal antibodies. In addition, these pseudo-particles allowed investigation of the role of putative HCV receptors. Although our results tend to confirm their involvement, they provide evidence that neither LDLr nor CD81 is sufficient to mediate HCV cell entry. Altogether, these studies indicate that these pseudo-particles may mimic the early infection steps of parental HCV and will be suitable for the development of much needed new antiviral therapies.
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            EphrinB2 is the entry receptor for Nipah virus, an emergent deadly paramyxovirus.

            Nipah virus (NiV) is an emergent paramyxovirus that causes fatal encephalitis in up to 70 percent of infected patients, and there is evidence of human-to-human transmission. Endothelial syncytia, comprised of multinucleated giant-endothelial cells, are frequently found in NiV infections, and are mediated by the fusion (F) and attachment (G) envelope glycoproteins. Identification of the receptor for this virus will shed light on the pathobiology of NiV infection, and spur the rational development of effective therapeutics. Here we report that ephrinB2, the membrane-bound ligand for the EphB class of receptor tyrosine kinases (RTKs), specifically binds to the attachment (G) glycoprotein of NiV. Soluble Fc-fusion proteins of ephrinB2, but not ephrinB1, effectively block NiV fusion and entry into permissive cell types. Moreover, transfection of ephrinB2 into non-permissive cells renders them permissive for NiV fusion and entry. EphrinB2 is expressed on endothelial cells and neurons, which is consistent with the known cellular tropism for NiV. Significantly, we find that NiV-envelope-mediated infection of microvascular endothelial cells and primary cortical rat neurons is inhibited by soluble ephrinB2, but not by the related ephrinB1 protein. Cumulatively, our data show that ephrinB2 is a functional receptor for NiV.
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              Transferrin receptor 1 is a cellular receptor for New World haemorrhagic fever arenaviruses

              Viral receptor identified The transferrin receptor 1 (TfR1) has been identified as the cellular receptor for four New World arenaviruses — the Junin, Machupo, Guanarito and Sabia viruses. This class of arenaviruses is important because they cause fatal haemorrhagic fevers. Treating cultured cells with an antibody against TfR1 blocks viral entry and replication. Antibodies that limit arenavirus replication without interfering with host iron metabolism may be effective in controlling outbreaks of New World haemorrhagic fever. Supplementary information The online version of this article (doi:10.1038/nature05539) contains supplementary material, which is available to authorized users.

                Author and article information

                Rev Med Virol
                Rev. Med. Virol
                Reviews in Medical Virology
                John Wiley and Sons Inc. (Hoboken )
                07 December 2017
                January 2018
                : 28
                : 1 ( doiID: 10.1002/rmv.v28.1 )
                [ 1 ] Division of HIV/AIDS and Sex‐Transmitted Virus Vaccines National Institutes for Food and Drug Control Beijing China
                [ 2 ] Division of Regulatory Research Centre for Biologics Evaluation, Biologics and Genetic Therapies Directorate, Health Canada Ottawa Canada
                Author notes
                [* ] Correspondence

                Youchun Wang, Division of HIV/AIDS and Sex‐Transmitted Virus Vaccines, National Institutes for Food and Drug Control, No. 31 Huatuo Road, Beijing 102629, China.

                Email: wangyc@ 123456nifdc.org.cn

                RMV1963 RMV-2017-036.R1
                Copyright © 2017 John Wiley & Sons, Ltd.

                This article is being made freely available through PubMed Central as part of the COVID-19 public health emergency response. It can be used for unrestricted research re-use and analysis in any form or by any means with acknowledgement of the original source, for the duration of the public health emergency.

                Page count
                Figures: 0, Tables: 3, Pages: 10, Words: 3611
                Custom metadata
                January 2018
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.8.0 mode:remove_FC converted:16.04.2020

                Microbiology & Virology

                vsv, hiv, lentiviral vector, mlv, packaging system, pseudovirus


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