scholarly journals The Lymphocytic Choriomeningitis Virus Matrix Protein PPXY Late Domain Drives the Production of Defective Interfering Particles

2016 ◽  
Vol 12 (3) ◽  
pp. e1005501 ◽  
Author(s):  
Christopher M. Ziegler ◽  
Philip Eisenhauer ◽  
Emily A. Bruce ◽  
Marion E. Weir ◽  
Benjamin R. King ◽  
...  
Keyword(s):  
Matrix Protein ◽  
Lymphocytic Choriomeningitis ◽  
Lymphocytic Choriomeningitis Virus ◽  
Defective Interfering Particles ◽  
Late Domain

scholarly journals Lassa Virus Vaccine Candidate ML29 Generates Truncated Viral RNAs Which Contribute to Interfering Activity and Attenuation

Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 214
Author(s):  
Dylan M. Johnson ◽  
Beatrice Cubitt ◽  
Tia L. Pfeffer ◽  
Juan Carlos de la Torre ◽  
Igor S. Lukashevich
Keyword(s):  
Matrix Protein ◽  
Fluorescent Protein ◽  
Vaccine Candidate ◽  
Small Animal ◽  
Lymphocytic Choriomeningitis ◽  
Lassa Virus ◽  
Defective Interfering Particles ◽  
Persistently Infected ◽  
Viral Genomes ◽  
Infected Cells

Defective interfering particles (DIPs) are naturally occurring products during virus replication in infected cells. DIPs contain defective viral genomes (DVGs) and interfere with replication and propagation of their corresponding standard viral genomes by competing for viral and cellular resources, as well as promoting innate immune antiviral responses. Consequently, for many different viruses, including mammarenaviruses, DIPs play key roles in the outcome of infection. Due to their ability to broadly interfere with viral replication, DIPs are attractive tools for the development of a new generation of biologics to target genetically diverse and rapidly evolving viruses. Here, we provide evidence that in cells infected with the Lassa fever (LF) vaccine candidate ML29, a reassortant that carries the nucleoprotein (NP) and glycoprotein (GP) dominant antigens of the pathogenic Lassa virus (LASV) together with the L polymerase and Z matrix protein of the non-pathogenic genetically related Mopeia virus (MOPV), L-derived truncated RNA species are readily detected following infection at low multiplicity of infection (MOI) or in persistently-infected cells originally infected at high MOI. In the present study, we show that expression of green fluorescent protein (GFP) driven by a tri-segmented form of the mammarenavirus lymphocytic choriomeningitis virus (r3LCMV-GFP/GFP) was strongly inhibited in ML29-persistently infected cells, and that the magnitude of GFP suppression was dependent on the passage history of the ML29-persistently infected cells. In addition, we found that DIP-enriched ML29 was highly attenuated in immunocompetent CBA/J mice and in Hartley guinea pigs. Likewise, STAT-1-/- mice, a validated small animal model for human LF associated hearing loss sequelae, infected with DIP-enriched ML29 did not exhibit any hearing abnormalities throughout the observation period (62 days).

Antiviral Effect of Interferon Lambda Against Lymphocytic Choriomeningitis Virus

2015 ◽  
Vol 35 (7) ◽  
pp. 540-553 ◽  
Author(s):  
Lubomira Lukacikova ◽  
Ingrid Oveckova ◽  
Tatiana Betakova ◽  
Katarina Laposova ◽  
Katarina Polcicova ◽  
...  
Keyword(s):  
Antiviral Effect ◽  
Lymphocytic Choriomeningitis ◽  
Lymphocytic Choriomeningitis Virus ◽  
Interferon Lambda

scholarly journals The Nucleoprotein Is Required for Lymphocytic Choriomeningitis Virus-Based Vaccine Vector Immunogenicity

2015 ◽  
Vol 89 (22) ◽  
pp. 11734-11738 ◽  
Author(s):  
Stephanie Darbre ◽  
Susan Johnson ◽  
Sandra Kallert ◽  
Paul-Henri Lambert ◽  
Claire-Anne Siegrist ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cell ◽  
T Cell Responses ◽  
Lymphocytic Choriomeningitis ◽  
Lymphocytic Choriomeningitis Virus ◽  
Viral Transcription ◽  
Genome Replication ◽  
Recombinant Glycoprotein ◽  
Cell Responses ◽  
Deficient Vector

Recombinant glycoprotein-deficient lymphocytic choriomeningitis virus-based vaccine vectors (rLCMV/ΔGP) are potent CD8+T cell inducers. To investigate the underlying molecular requirements, we generated a nucleoprotein-deficient vector counterpart (rLCMV/ΔNP). NP but not GP is a minimaltrans-acting factor for viral transcription and genome replication. We found that, unlike rLCMV/ΔGP, rLCMV/ΔNP failed to elicit detectable CD8+T cell responses unless NP wastranscomplemented in a transgenic host. Hence, NP-dependent intracellular gene expression is essential for LCMV vector immunogenicity.

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