Rift Valley fever virus NSs protein functions and the similarity to other bunyavirus NSs proteins

Ly, Hoai J.; Ikegami, Tetsuro

doi:10.1186/s12985-016-0573-8

Cited by 85 publications

(84 citation statements)

References 139 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Bunyavirus NSs proteins play an important role in hijacking host cells, although NSs proteins have low homology of amino acid sequences among bunyaviruses (42). Indeed, NSs proteins (43). The naturally attenuated RVFV strain clone 13 has a truncated defective NSs protein and exhibits lower virulence than the virulent RVFV strain ZH548, with intact NSs protein.…”

Section: Discussionmentioning

confidence: 99%

RIG-I-Like Receptor and Toll-Like Receptor Signaling Pathways Cause Aberrant Production of Inflammatory Cytokines/Chemokines in a Severe Fever with Thrombocytopenia Syndrome Virus Infection Mouse Model

Yamada

Shimojima

Narita

et al. 2018

J Virol

View full text Add to dashboard Cite

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by a tick-borne phlebovirus of the family , SFTS virus (SFTSV). Wild-type and type I interferon (IFN-I) receptor 1-deficient (IFNAR1) mice have been established as nonlethal and lethal models of SFTSV infection, respectively. However, the mechanisms of IFN-I production and the factors causing the lethal disease are not well understood. Using bone marrow-chimeric mice, we found that IFN-I signaling in hematopoietic cells was essential for survival of lethal SFTSV infection. The disruption of IFN-I signaling in hematopoietic cells allowed an increase in viral loads in serum and produced an excess of multiple inflammatory cytokines and chemokines. The production of IFN-I and inflammatory cytokines was abolished by deletion of the signaling molecules IPS-1 and MyD88, essential for retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) and Toll-like receptor (TLR) signaling, respectively. However, IPS-1 MyD88 mice exhibited resistance to lethal SFTS with a moderate viral load in serum. Taken together, these results indicate that adequate activation of RLR and TLR signaling pathways under low to moderate levels of viremia contributed to survival through the IFN-I-dependent antiviral response during SFTSV infection, whereas overactivation of these signaling pathways under high levels of viremia resulted in abnormal induction of multiple inflammatory cytokines and chemokines, causing the lethal disease. SFTSV causes a severe infectious disease in humans, with a high fatality rate of 12 to 30%. To know the pathogenesis of the virus, we need to clarify the innate immune response as a front line of defense against viral infection. Here, we report that a lethal animal model showed abnormal induction of multiple inflammatory cytokines and chemokines by an uncontrolled innate immune response, which triggered the lethal SFTS. Our findings suggest a new strategy to target inflammatory humoral factors to treat patients with severe SFTS. Furthermore, this study may help the investigation of other tick-borne viruses.

show abstract

Section: Discussionmentioning

confidence: 99%

RIG-I-Like Receptor and Toll-Like Receptor Signaling Pathways Cause Aberrant Production of Inflammatory Cytokines/Chemokines in a Severe Fever with Thrombocytopenia Syndrome Virus Infection Mouse Model

Yamada

Shimojima

Narita

et al. 2018

J Virol

View full text Add to dashboard Cite

show abstract

“…With the exception of Anopheles A, Anopheles B, and Tete serogroups, the orthobuyaviruses code for an NSs protein by overlapping the ORF with the NP (Mohamed et al, 2009). Bunyavirus NSs play an eminent role in inhibiting the interferon response (Ly and Ikegami, 2016;Schoen and Weber, 2015) and in plants (for tospovirus) interferes the plant antiviral RNA silencing (Hedil and Kormelink, 2016). NSm proteins instead are integral membrane proteins with an unclear general role among bunyavirus.…”

Section: Bunyavirusesmentioning

confidence: 99%

Transcription and replication mechanisms of Bunyaviridae and Arenaviridae L proteins

et al. 2017

View full text Add to dashboard Cite

Bunyaviridae and Arenaviridae virus families include an important number of highly pathogenic viruses for humans. They are enveloped viruses with negative stranded RNA genomes divided into three (bunyaviruses) or two (arenaviruses) segments. Each genome segment is coated by the viral nucleoproteins (NPs) and the polymerase (L protein) to form a functional ribonucleoprotein (RNP) complex. The viral RNP provides the necessary context on which the L protein carries out the biosynthetic processes of RNA replication and gene transcription. Decades of research have provided a good understanding of the molecular processes underlying RNA synthesis, both RNA replication and gene transcription, for these two families of viruses. In this review we will provide a global view of the common features, as well as differences, of the molecular biology of Bunyaviridae and Arenaviridae. We will also describe structures of protein and protein-RNA complexes so far determined for these viral families, mainly focusing on the L protein, and discuss their implications for understanding the mechanisms of viral RNA replication and gene transcription within the architecture of viral RNPs, also taking into account the cellular context in which these processes occur. Finally, we will discuss the implications of these structural findings for the development of antiviral drugs to treat human diseases caused by members of the Bunyaviridae and Arenaviridae families.

show abstract

“…In addition to TOSV, several other phleboviruses have been reported to counteract the IFN antiviral response [16,42]. Often, virulence seems to correlate with the capacity of phleboviruses to block the IFN pathway and the innate immunity in general [16,18,39,[42][43][44]. The present study provides a toolbox that will lay the basis for future research, not only on the interplay between TOSV infection and innate immunity, but also on the basic molecular and cellular mechanisms governing TOSV entry, replication, assembly, and egress.…”

Section: Discussionmentioning

confidence: 99%

Novel Toscana Virus Reverse Genetics System Establishes NSs as an Antagonist of Type I Interferon Responses

Woelfl

Léger

Oreshkova

et al. 2020

Viruses

View full text Add to dashboard Cite

The sand fly-borne Toscana virus (TOSV) is the major cause of human meningoencephalitis in the Mediterranean basin during the summer season. In this work, we have developed a T7 RNA polymerase-driven reverse genetics system to recover infectious particles of a lineage B strain of TOSV. The viral protein pattern and growth properties of the rescued virus (rTOSV) were found to be similar to those of the corresponding wild-type (wt) virus. Using this system, we genetically engineered a TOSV mutant lacking expression of the non-structural protein NSs (rTOSV Viruses 2019, 11, x FOR PEER REVIEW and Proteomics Core Facility of the German Cancer Research Center, Heidelberg (Table 1). B viruses were produced and purified, as described in Section 2.5. Soluble ectodomains of GN a were stably expressed in drosophila S2 cells and purified according to a standard procedure Using these protocols, the protein purity reached over 90%. Antisera were prepared in guinea by injecting 100 µg of Triton X-100-inactivated purified viruses or soluble ectodomains of GN a in Freund's complete adjuvant. The priming was followed by three booster injections of 100 µg week intervals, the first one in Freund's incomplete adjuvant, and the others in phosphate-bu saline (PBS). Animals were bled before the first immunization (control pre-immune serum) days after the last injection. The purified rabbit polyclonal antibodies against the TOSV nucleop N (T4) and non-structural protein NSs (T5) were developed by GenScript (Piscataway Netherlands). Rabbits were immunized with either a peptide corresponding to the C termin amino acid residues of NSs or the full-length N protein with a C-terminal His-tag. The m immune ascitic fluid against all TOSV structural proteins was a generous gift from R.B. (University of Texas, Galveston, Texas, USA). s were constructed by GenScript. Briefly, the cDNAs encoding the full-length S, M, and f TOSV, flanked by an upstream T7 polymerase promoter sequence and a downstream ta virus (HdV) ribozyme sequence ( Figure S1), were synthesized. The gene synthesis e subjected to blunt-end ligation into EcoRV-linearized pUC57 plasmid, or alternatively, into the pCC1 plasmid, using the CloneEZ PCR Cloning Kit (Genscript), resulting in C1-M, and pUC57-L. In addition, a pUC57-SɸNSs was created in which the S segment mRNA, with the 18 first AUG codons replaced by UAG stop codons ( Figure S2). Viruses from Plasmid DNAscells expressing T7 polymerase were seeded in 6-well plates (2.5 × 10 5 cells per well). g day, rTOSV was rescued from cells by transfection with 1 µg each of the plasmids C1-M, and pUC57-L. Alternatively, the recovery of rTOSVɸNSs was achieved following thod but using the plasmid pUC57-SɸNSs instead of the pUC57-S. Transfection was ith Lipofectamine 2000 (Thermo Fisher Scientific), using a ratio of 1 µL Lipofectamine of plasmids in 400 µL of complete GMEM without antibiotics. Supernatants were fresh culture medium containing antibiotics and 2% serum 4 h post-transfection. Five nsfection, supernatants were harvested, c...

show abstract

Rift Valley fever virus NSs protein functions and the similarity to other bunyavirus NSs proteins

Cited by 85 publications

References 139 publications

RIG-I-Like Receptor and Toll-Like Receptor Signaling Pathways Cause Aberrant Production of Inflammatory Cytokines/Chemokines in a Severe Fever with Thrombocytopenia Syndrome Virus Infection Mouse Model

RIG-I-Like Receptor and Toll-Like Receptor Signaling Pathways Cause Aberrant Production of Inflammatory Cytokines/Chemokines in a Severe Fever with Thrombocytopenia Syndrome Virus Infection Mouse Model

Transcription and replication mechanisms of Bunyaviridae and Arenaviridae L proteins

Novel Toscana Virus Reverse Genetics System Establishes NSs as an Antagonist of Type I Interferon Responses

Contact Info

Product

Resources

About