期刊
VIRUSES-BASEL
卷 4, 期 10, 页码 2137-2161出版社
MDPI AG
DOI: 10.3390/v4102137
关键词
lymphocytic choriomeningitis virus; nucleoprotein; Z matrix protein; self-association; viral-like particles; minigenome; type I Interferon; double-stranded RNA; dominant negative
类别
资金
- Institutional Ruth L. Kirschstein National Research Service Award [GM068411]
- NIH [RO1 AI077719, R21NS075611-01, R03AI099681-01A1, HHSN272201000055C]
- NIH/NIAID [RO1 AI077719, RO1 AI047140, RO1 AI079665]
- Fulbright-Conicyt fellowship
Arenaviruses merit significant interest because several family members are etiological agents of severe hemorrhagic fevers, representing a major burden to public health. Currently, there are no FDA-licensed vaccines against arenaviruses and the only available antiviral therapy is limited to the use of ribavirin that is partially effective. Arenavirus nucleoprotein (NP) is found associated with the genomic RNA forming the viral ribonucleoproteins (vRNPs) that together with the polymerase (L) direct viral replication and transcription. Virion formation requires the recruitment of vRNPs into budding sites, a process in which the arenavirus matrix-like protein (Z) plays a major role. Therefore, proper NP-NP and NP-Z interactions are required for the generation of infectious progeny. In this work we demonstrate the role of the amino acid residue D471 in the self-association of lymphocytic choriomeningitis virus nucleoprotein (LCMV-NP). Amino acid substitutions at this position abrogate NP oligomerization, affecting its ability to mediate replication and transcription of a minigenome reporter plasmid. However, its ability to interact with the Z protein, counteract the cellular interferon response and bind to dsRNA analogs was retained. Additionally, we also document the dominant negative effect of D471G mutation on viral infection, suggesting that NP self-association is an excellent target for the development of new antivirals against arenaviruses.
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