Rift Valley fever virus modulates apoptosis and immune response during infection of human astrocytes

Quellec, Jordan; Pédarrieu, Aurélie; Piro-Mégy, Camille; Barthélémy, Jonathan; Simonin, Yannick; Salinas, Sara; Cêtre-Sossah, Catherine

doi:10.1080/22221751.2023.2207672

Cited by 5 publications

(5 citation statements)

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“…RVFV nonstructural protein NSs forms nuclear filaments [27], which are required for pathogenesis [28], and it was recently shown that NSs interacts with active caspase 3 within these filaments [29, 30]. Using immunofluorescent microscopy, we stained infected and mock-infected rat BSCs with anti-RVFV N, anti-beta III tubulin, and anti-active caspase 3 antibodies.…”

Section: Resultsmentioning

confidence: 99%

“…Previous literature suggest that RVFV readily infects neurons, microglia, and astrocytes in vitro and in vivo , resulting in a highly inflammatory environment including cell death and cytokine dysregulation [6, 7, 10, 12, 29, 36]. In particular, GRO/KC, IL-1β and MCP-1 are produced at high levels at end-stage disease in the brain of rats infected with RVFV by inhalational exposure [12].…”

Section: Discussionmentioning

confidence: 99%

“…We stained BSCs for active caspase 3, a marker of apoptosis and found positive staining in filamentous structures within the nuclei of RVFV-infected cells. It has recently been shown that caspase 3 is activated and translocated to the nucleus where it co-localizes with the nonstructural protein NSs [29]. The rat BSC model offers an additional tool to study the mechanism of this viral–host interaction.…”

Section: Discussionmentioning

confidence: 99%

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Acute Rift Valley fever virus infection induces inflammatory cytokines and cell death in ex vivo rat brain slice culture

Connors,

Frey,

Demers

et al. 2024

Journal of General Virology

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Rift Valley fever virus (RVFV) is an emerging arboviral disease with pandemic potential. While infection is often self-limiting, a subset of individuals may develop late-onset encephalitis, accounting for up to 20 % of severe cases. Importantly, individuals displaying neurologic disease have up to a 53 % case fatality rate, yet the neuropathogenesis of RVFV infection remains understudied. In this study, we evaluated whether ex vivo postnatal rat brain slice cultures (BSCs) could be used to evaluate RVFV infection in the central nervous system. BSCs mounted an inflammatory response after slicing, which resolved over time, and they were viable in culture for at least 12 days. Infection of rat BSCs with pathogenic RVFV strain ZH501 induced tissue damage and apoptosis over 48 h. Viral replication in BSCs reached up to 1×107 p.f.u. equivalents/ml, depending on inoculation dose. Confocal immunofluorescent microscopy of cleared slices confirmed direct infection of neurons as well as activation of microglia and astrocytes. Further, RVFV-infected rat BSCs produced antiviral cytokines and chemokines, including MCP-1 and GRO/KC. This study demonstrates that rat BSCs support replication of RVFV for ex vivo studies of neuropathogenesis. This allows for continued and complementary investigation into RVFV infection in an ex vivo postnatal brain slice culture format.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Acute Rift Valley fever virus infection induces inflammatory cytokines and cell death in ex vivo rat brain slice culture

Connors,

Frey,

Demers

et al. 2024

Journal of General Virology

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“…Loss of p53 reduces the replication of RVFV and RVFV-induced cell death, presumably by manipulating the p53-dependent apoptosis signal pathway [ 141 , 143 ]. In addition, RVFV triggers cell apoptosis in astrocytes, whereas the RVFV NSs protein may hinder apoptosis by sequestering activated caspase-3 within the nucleus [ 144 , 145 ]. During SFTSV infection, apoptosis may be appropriately repressed or minimally enhanced in monocytes [ 59 , 146 ], whereas severe apoptosis is triggered in peripheral monocytes from SFTS patient at the early stage of fatal SFTSV infection [ 147 ].…”

Section: Apoptosis Is Beneficial For the Replication Of Phenuivirus R...mentioning

confidence: 99%

Current insights into human pathogenic phenuiviruses and the host immune system

Zhou,

Jiang,

Liu

et al. 2024

Virulence

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Phenuiviruses are a class of segmented negative-sense single-stranded RNA viruses, typically consisting of three RNA segments that encode four distinct proteins. The emergence of pathogenic phenuivirus strains, such as Rift Valley fever phlebovirus (RVFV) in sub-Saharan Africa, Severe Fever with Thrombocytopenia Syndrome Virus (SFTSV) in East and Southeast Asia, and Heartland Virus (HRTV) in the United States has presented considerable challenges to global public health in recent years. The innate immune system plays a crucial role as the initial defense mechanism of the host against invading pathogens. In addition to continued research aimed at elucidating the epidemiological characteristics of phenuivirus, significant advancements have been made in investigating its viral virulence factors (glycoprotein, non-structural protein, and nucleoprotein) and potential host–pathogen interactions. Specifically, efforts have focused on understanding mechanisms of viral immune evasion, viral assembly and egress, and host immune networks involving immune cells, programmed cell death, inflammation, nucleic acid receptors, etc. Furthermore, a plethora of technological advancements, including metagenomics, metabolomics, single-cell transcriptomics, proteomics, gene editing, monoclonal antibodies, and vaccines, have been utilized to further our understanding of phenuivirus pathogenesis and host immune responses. Hence, this review aims to provide a comprehensive overview of the current understanding of the mechanisms of host recognition, viral immune evasion, and potential therapeutic approaches during human pathogenic phenuivirus infections focusing particularly on RVFV and SFTSV.

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“…Recently, Quellec et al (2023) showed that RVFV-infected astrocytes upregulated expression of genes associated with inflammatory and type I interferon responses at the mRNA level but not at the protein level [10].…”

Section: Introductionmentioning

confidence: 99%

Rift Valley Fever Virus: An Overview of the Current Status of Diagnostics

Lapa,

Pauciullo,

Ricci

et al. 2024

Biomedicines

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Rift Valley fever is a vector-borne zoonotic disease caused by the Rift Valley fever virus (Phlebovirus genus) listed among the eight pathogens included in the Bluepoint list by the WHO. The transmission is mainly vehicled by Aedes and Culex mosquito species. Symptoms of the disease are varied and non-specific, making clinical diagnosis often challenging, especially in the early stages. Due to the difficulty in distinguishing Rift Valley fever from other viral hemorrhagic fevers, as well as many other diseases that cause fever, an early diagnosis of the infection is important to limit its spread and to provide appropriate care to patients. To date, there is no validated point-of-care diagnostic tool. The virus can only be detected in the blood for a brief period, suggesting that molecular methods alone are not sufficient for case determination. For this, it is preferable to combine both molecular and serological tests. The wide distribution of competent vectors in non-endemic areas, together with global climate change, elicit the spread of RVFV to continents other than Africa, making surveillance activities vital to prevent or to limit the impact of human outbreaks and for a rapid identification of positive cases, making diagnosis a key factor for this achievement.

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Rift Valley fever virus modulates apoptosis and immune response during infection of human astrocytes

Cited by 5 publications

References 56 publications

Acute Rift Valley fever virus infection induces inflammatory cytokines and cell death in ex vivo rat brain slice culture

Acute Rift Valley fever virus infection induces inflammatory cytokines and cell death in ex vivo rat brain slice culture

Current insights into human pathogenic phenuiviruses and the host immune system

Rift Valley Fever Virus: An Overview of the Current Status of Diagnostics

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