scholarly journals MAVS mediates a protective immune response in the brain to Rift Valley fever virus

2021 ◽  
Author(s):  
Dina R. Weilhammer ◽  
Nicholas R. Hum ◽  
Feliza A. Bourguet ◽  
Aimy Sebastian ◽  
Doris Lam ◽  
...  
Keyword(s):  
Immune Response ◽  
Rift Valley ◽  
Rift Valley Fever ◽  
Molecular Mechanisms ◽  
Rift Valley Fever Virus ◽  
Fever Virus ◽  
Type I ◽  
Activation Markers ◽  
Valley Fever ◽  
The Brain

Rift Valley fever virus (RVFV) is a highly pathogenic mosquito-borne virus capable of causing hepatitis, encephalitis, blindness, hemorrhagic syndrome, and death in humans and livestock. Upon aerosol infection with RVFV, the brain is a major site of viral replication and tissue damage, yet pathogenesis in this organ has been understudied. Here, we investigated the immune response in the brain of RVFV infected mice. In response to infection, microglia initiate robust transcriptional upregulation of antiviral immune genes, as well as increased levels of activation markers and cytokine secretion that is dependent on mitochondrial antiviral-signaling protein (MAVS) and independent of toll-like receptors 3 and 7. In vivo, Mavs-/- mice displayed enhanced susceptibility to RVFV as determined by increased brain viral burden and higher mortality. Single-cell RNA sequence analysis identified microglia-specific defects in type I interferon and interferon responsive gene expression in Mavs-/- mice, as well as dysregulated lymphocyte infiltration. The results of this study provide a crucial step towards understanding the precise molecular mechanisms by which RVFV infection is controlled in the brain and will help inform the development of vaccines and antiviral therapies that are effective in preventing encephalitis.

scholarly journals MVA Vectored Vaccines Encoding Rift Valley Fever Virus Glycoproteins Protect Mice against Lethal Challenge in the Absence of Neutralizing Antibody Responses

Vaccines ◽  
2020 ◽  
Vol 8 (1) ◽  
pp. 82 ◽  
Author(s):  
Elena López-Gil ◽  
Sandra Moreno ◽  
Javier Ortego ◽  
Belén Borrego ◽  
Gema Lorenzo ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Cellular Immunity ◽  
Rift Valley ◽  
Neutralizing Antibodies ◽  
Rift Valley Fever ◽  
Rift Valley Fever Virus ◽  
Fever Virus ◽  
Valley Fever

In vitro neutralizing antibodies have been often correlated with protection against Rift Valley fever virus (RVFV) infection. We have reported previously that a single inoculation of sucrose-purified modified vaccinia Ankara (MVA) encoding RVFV glycoproteins (rMVAGnGc) was sufficient to induce a protective immune response in mice after a lethal RVFV challenge. Protection was related to the presence of glycoprotein specific CD8+ cells, with a low-level detection of in vitro neutralizing antibodies. In this work we extended those observations aimed to explore the role of humoral responses after MVA vaccination and to study the contribution of each glycoprotein antigen to the protective efficacy. Thus, we tested the efficacy and immune responses in BALB/c mice of recombinant MVA viruses expressing either glycoprotein Gn (rMVAGn) or Gc (rMVAGc). In the absence of serum neutralizing antibodies, our data strongly suggest that protection of vaccinated mice upon the RVFV challenge can be achieved by the activation of cellular responses mainly directed against Gc epitopes. The involvement of cellular immunity was stressed by the fact that protection of mice was strain dependent. Furthermore, our data suggest that the rMVA based single dose vaccination elicits suboptimal humoral immune responses against Gn antigen since disease in mice was exacerbated upon virus challenge in the presence of rMVAGnGc or rMVAGn immune serum. Thus, Gc-specific cellular immunity could be an important component in the protection after the challenge observed in BALB/c mice, contributing to the elimination of infected cells reducing morbidity and mortality and counteracting the deleterious effect of a subneutralizing antibody immune response.

scholarly journals The Change P82L in the Rift Valley Fever Virus NSs Protein Confers Attenuation in Mice Not Related with a Type-I IFN Antagonistic Phenotype

2021 ◽  
Author(s):  
Belén Borrego ◽  
Sandra Moreno ◽  
Nuria de la Losa ◽  
Friedemann Weber ◽  
Alejandro Brun
Keyword(s):  
Amino Acid ◽  
Rift Valley ◽  
Rift Valley Fever ◽  
Rift Valley Fever Virus ◽  
Fever Virus ◽  
Single Amino Acid ◽  
Economic Losses ◽  
Type I ◽  
Valley Fever

Rift valley fever virus (RVFV) is a mosquito-borne bunyavirus that causes an important disease in ruminants, with great economic losses. The infection can be also transmitted to humans; therefore it is considered a major threat to both human and animal health. In a previous work, we described a novel RVFV variant selected in cell culture in the presence of the antiviral agent favipiravir that was highly attenuated in vivo. This variant displayed 24 amino acid substitutions in different viral proteins when compared to its parental viral strain, two of them located in the NSs protein that is known to be the major virulence factor of RVFV. By means of a reverse genetics system, in this work we have analyzed the effect that one of these substitutions, P82L, has in viral attenuation in vivo. Rescued viruses carrying this single amino acid change were clearly attenuated in BALB/c mice while their growth in an IFN-competent cell line as well as the production of IFN-β did not seem to be affected. However, the pattern of nuclear NSs accumulation was modified in cells infected with the mutant viruses. These results unveil a new RVFV virulence marker highlighting the multiple ways of NSs protein to modulate viral infectivity.

Microencapsulated plasmids expressing Gn and Gc glycoproteins of Rift Valley Fever virus enhance humoral immune response in mice

2020 ◽  
Vol 42 (4) ◽  
pp. 529-536
Author(s):  
Oxana Selina ◽  
Ilnaz Imatdinov ◽  
Vera Balysheva ◽  
Roman Akasov ◽  
Alexander Kryukov ◽  
...  
Keyword(s):  
Immune Response ◽  
Humoral Immune Response ◽  
Rift Valley ◽  
Rift Valley Fever ◽  
Rift Valley Fever Virus ◽  
Fever Virus ◽  
Valley Fever ◽  
Humoral Immune

scholarly journals Innate Immune Response to Rift Valley Fever Virus in Goats

2012 ◽  
Vol 6 (4) ◽  
pp. e1623 ◽  
Author(s):  
Charles K. Nfon ◽  
Peter Marszal ◽  
Shunzhen Zhang ◽  
Hana M. Weingartl
Keyword(s):  
Immune Response ◽  
Innate Immune Response ◽  
Rift Valley ◽  
Rift Valley Fever ◽  
Rift Valley Fever Virus ◽  
Innate Immune ◽  
Fever Virus ◽  
Valley Fever

scholarly journals Resistance to Rift Valley fever virus in Rattus norvegicus: genetic variability within certain ‘inbred’ strains

2000 ◽  
Vol 81 (11) ◽  
pp. 2683-2688 ◽  
Author(s):  
Marcus Ritter ◽  
Michèle Bouloy ◽  
Pierre Vialat ◽  
Christian Janzen ◽  
Otto Haller ◽  
...  
Keyword(s):  
Rift Valley ◽  
Rift Valley Fever ◽  
Rift Valley Fever Virus ◽  
Fever Virus ◽  
Sub Saharan Africa ◽  
Type I ◽  
Rat Strains ◽  
Valley Fever ◽  
Inbred Rat Strains ◽  
Inbred Rat

Rift Valley fever virus (RVFV) is the causative agent of Rift Valley fever, a widespread disease of domestic animals and humans in sub-Saharan Africa. Laboratory rats have frequently been used as an animal model for studying the pathogenesis of Rift Valley fever. It is shown here that Lewis rats (LEW/mol) are susceptible to infection with RVFV, whereas Wistar–Furth (WF/mol) rats are resistant to RVFV infection. LEW/mol rats developed acute hepatitis and died after infection with RVFV strain ZH548, whereas WF/mol rats survived the infection. Cross-breeding of resistant WF/mol rats with susceptible LEW/mol rats demonstrated that resistance is segregated as a single dominant gene. Primary hepatocytes but not glial cells from WF/mol rats showed the resistant phenotype in cell culture, indicating that resistance was cell type-specific. Moreover, when cultured hepatocytes were stimulated with interferon (IFN) type I there was no indication of a regulatory role of IFN in the RVFV-resistance gene expression in WF/mol rats. Interestingly, previous reports have shown that LEW rats from a different breeding stock (LEW/mai) are resistant to RVFV infections, whereas WF/mai rats are susceptible. Thus, inbred rat strains seem to differ in virus susceptibility depending on their breeding histories. A better genetic characterization of inbred rat strains and a revision in nomenclature is needed to improve animal experimentation in the future.

scholarly journals A Hyper-Attenuated Variant of Rift Valley Fever Virus Generated by a Mutagenic Drug (Favipiravir) Unveils Potential Virulence Markers

2021 ◽  
Vol 11 ◽  
Author(s):  
Belén Borrego ◽  
Alejandro Brun
Keyword(s):  
Rift Valley ◽  
Rift Valley Fever ◽  
Rift Valley Fever Virus ◽  
Fever Virus ◽  
Economic Losses ◽  
Type I ◽  
Valley Fever ◽  
Virulence Markers ◽  
Drug Concentrations

Rift Valley fever virus (RVFV) is a mosquito-borne bunyavirus that causes Rift Valley fever (RVF), a zoonotic disease of wild and domestic ruminants, causing serious economic losses and a threat to human health that could be controlled by vaccination. Though RVF vaccines are available for livestock, no RVF vaccines have been licensed for veterinary use in non-endemic countries nor for human populations in RVF risk areas. In a recent work, we showed that favipiravir, a promising drug with antiviral activity against a number of RNA viruses, led to the extinction of RVFV from infected cell cultures. Nevertheless, certain drug concentrations allowed the recovery of a virus variant showing increased resistance to favipiravir. In this work, we characterized this novel resistant variant both at genomic and phenotypic level in vitro and in vivo. Interestingly, the resistant virus displayed reduced growth rates in C6/36 insect cells but not in mammalian cell lines, and was highly attenuated but still immunogenic in vivo. Some amino acid substitutions were identified in the viral RNA-dependent RNA-polymerase (RdRp) gene and in the virus encoded type I-interferon (IFN-I) antagonist NSs gene, in catalytic core motifs and nuclear localization associated positions, respectively. These data may help to characterize novel potential virulence markers, offering additional strategies for further safety improvements of RVF live attenuated vaccine candidates.

scholarly journals Vascular permeability in the brain is a late pathogenic event during Rift Valley fever virus encephalitis in rats

Virology ◽  
2019 ◽  
Vol 526 ◽  
pp. 173-179 ◽  
Author(s):  
Aaron W. Walters ◽  
Michael R. Kujawa ◽  
Joseph R. Albe ◽  
Douglas S. Reed ◽  
William B. Klimstra ◽  
...  
Keyword(s):  
Vascular Permeability ◽  
Rift Valley ◽  
Rift Valley Fever ◽  
Rift Valley Fever Virus ◽  
Fever Virus ◽  
Valley Fever ◽  
Virus Encephalitis ◽  
The Brain

scholarly journals Pathogen-specific resistance to Rift Valley fever virus infection is induced in mosquito cells by expression of the recombinant nucleoprotein but not NSs non-structural protein sequences

2000 ◽  
Vol 81 (9) ◽  
pp. 2161-2166 ◽  
Author(s):  
A. Billecocq ◽  
M. Vazeille-Falcoz ◽  
F. Rodhain ◽  
M. Bouloy
Keyword(s):  
Rift Valley ◽  
Rift Valley Fever ◽  
Molecular Mechanisms ◽  
Rift Valley Fever Virus ◽  
Mosquito Species ◽  
Disease Outbreaks ◽  
Fever Virus ◽  
Structural Protein ◽  
Valley Fever ◽  
Mosquito Cells

Rift Valley fever virus (RVFV) is an arbovirus of the Bunyaviridae family, causing recurrent disease outbreaks in Africa. Natural vertebrate hosts include cattle and humans. Several mosquito species belonging to the Aedes and Culex generaact as vectors of this phlebovirus. To test whether pathogen-derived resistance against RVFV could be induced by expressing genomic sequences in mosquito cells, as has been shown for La Crosse and dengue 2 viruses, we generated various recombinant Semliki Forest viruses expressing the S segment (or its genes) in the genomic or antigenomic sense. Expression of the N but not the NSs gene interfered with the production of RVFV in mosquito cells and this phenomenon was RNA- but not protein-dependent. These results raise questions on the molecular mechanisms involved in virus resistance.

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