Nolwenn Jouvenet

Nolwenn Jouvenet
Institut Pasteur

PhD in virology

About

86
Publications
11,369
Reads
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3,932
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Introduction
I'm exploring interactions between flaviviruses (Yellow fever, Dengue, Zika and West Nile viruses) and their mammalian and arthropod-hosts. On-going projects focus on deciphering mechanisms underlying virus-induced innate immunity and inflammation, using biochemical, virological and microscopic assays combined with high-throughput screening methods. By providing a deeper understanding of flavivirus–host cell interactions, we hope to contribute to the development of effective antiviral therapies
Additional affiliations
January 2012 - present
Institut Pasteur International Network
Position
  • Group Leader
January 2005 - April 2011
The Rockefeller University
Position
  • PostDoc Position
June 2001 - November 2004
The Pirbright Institute
Position
  • PhD Student

Publications

Publications (86)
Article
Full-text available
Zika virus (ZIKV) is a flavivirus transmitted by mosquito bites that have spread to the Pacific Islands and the Americas over the past decade. The infection remains asymptomatic in most cases but can cause severe neurological disorders.
Article
Full-text available
Pattern recognition receptors (PRRs) protect against microbial invasion by detecting specific molecular patterns found in pathogens and initiating an immune response. Although microbial-derived PRR ligands have been extensively characterized, the contribution and relevance of endogenous ligands to PRR activation remains overlooked. Here, we charact...
Article
Full-text available
Interferon restricts SARS-CoV-2 replication in cell culture, but only a handful of Interferon Stimulated Genes with antiviral activity against SARS-CoV-2 have been identified. Here, we describe a functional CRISPR/Cas9 screen aiming at identifying SARS-CoV-2 restriction factors. We identify DAXX, a scaffold protein residing in PML nuclear bodies kn...
Preprint
Detailed knowledge of cellular networks that are modulated by Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is needed to understand viral replication and host response. So far, transcriptomic analyses of interactions between SARS-CoV-2 and cells were performed on mixed populations of infected and uninfected cells or using single-cell...
Article
Full-text available
SARS-CoV-2 infection results in impaired interferon response in patients with severe COVID-19. However, how SARS-CoV-2 interferes with host immune responses is incompletely understood. Here, we sequence small RNAs from SARS-CoV-2-infected human cells and identify a microRNA (miRNA) derived from a recently evolved region of the viral genome. We show...
Article
Interferons are our first line of defense against invading viruses. However, viruses encode effector proteins that can modulate human interferon responses. In this forum article, we highlight important discoveries and discuss outstanding questions that will enable us to better understand the nuances of this evolutionary battle between interferons a...
Article
Full-text available
Zika virus (ZIKV) infection has been associated with a series of neurological pathologies. In patients with ZIKV-induced neurological disorders, the virus is detectable in the central nervous system. Thus, ZIKV is capable of neuroinvasion, presumably through infection of the endothelial cells that constitute the blood-brain barrier (BBB). We demons...
Preprint
SARS-CoV-2 infection results in impaired interferon response in severe COVID-19 patients. However, how SARS-CoV-2 interferes with host immune response is incompletely understood. Here, we sequenced small RNAs from SARS-CoV-2-infected human cells and identified a micro RNA (miRNA) encoded in a recently evolved region of the viral genome. We show tha...
Article
Full-text available
RT-qPCR detection of SARS-CoV-2 RNA still represents the method of reference to diagnose and monitor COVID-19. From the onset of the pandemic, however, doubts have been expressed concerning the sensitivity of this molecular diagnosis method. Droplet digital PCR (ddPCR) is a third-generation PCR technique that is particularly adapted to detecting lo...
Article
Full-text available
Establishment of the interferon (IFN)-mediated antiviral state provides a crucial initial line of defense against viral infection. Numerous genes that contribute to this antiviral state remain to be identified. Using a loss-of-function strategy, we screened an original library of 1156 siRNAs targeting 386 individual curated human genes in stimulate...
Preprint
Full-text available
Establishment of the interferon (IFN)-mediated antiviral state provides a crucial initial line of defense against viral infection. Numerous genes that contribute to this antiviral state remain to be identified. Using a loss-of-function strategy, we screened an original library of 1156 siRNAs targeting 386 individual curated human genes in stimulate...
Preprint
Full-text available
Bats are natural reservoirs of numerous coronaviruses, including the potential ancestor of SARS-CoV-2. Knowledge concerning the interaction between coronaviruses and bat cells is sparse. We investigated the susceptibility of primary cells from Rhinolophus ferrumequinum and Myotis species, as well as of established and novel cell lines from Myotis m...
Preprint
While interferon restricts SARS-CoV-2 replication in cell culture, only a handful of Interferon Stimulated Genes with antiviral activity against SARS-CoV-2 have been identified. Here, we describe a functional CRISPR/Cas9 screen aiming at identifying SARS-CoV-2 restriction factors. We identified DAXX, a scaffold protein residing in PML nuclear bodie...
Article
Full-text available
Mass vaccination with the live attenuated vaccine YF-17D is the current way to prevent infection with Yellow fever virus (YFV). However, 0.000012–0.00002% of vaccinated patients develop post-vaccination neurological syndrome (YEL-AND). Understanding the factors responsible for neuroinvasion, neurotropism, and neurovirulence of the vaccine is critic...
Article
We thank A. Kohl (MRC—University of Glasgow Centre for Virus Research, United Kingdom) and Rafael Freitas de Oliveira Franca (FIOCRUZ, Recife, Brazil) for the Brazilian clinical isolate (PE243_KX197192), P. Despres (PIMIT, Université de La Réunion-INSERM France) for providing the pan-flavivirus antibody (4G2), and V. M. Cao-Lormeau and D. Musso, In...
Article
Full-text available
Hepatitis C virus (HCV) infection triggers Golgi fragmentation through the Golgi-resident protein immunity-related GTPase M (IRGM). Here, we report the role of NLRP3 (NOD-, LRR- and pyrin domain-containing protein 3) and ASC (Apoptosis-associated speck-like protein containing a CARD), two inflammasome components, in the initial events leading to th...
Article
Full-text available
The COVID-19 (Coronavirus disease-2019) pandemic, caused by the SARS-CoV-2 coronavirus, is a significant threat to public health and the global economy. SARS-CoV-2 is closely related to the more lethal but less transmissible coronaviruses SARS-CoV-1 and MERS-CoV. Here, we have carried out comparative viral-human protein-protein interaction and vira...
Article
Yellow fever is a mosquito-borne acute hemorrhagic disease caused by yellow fever virus (YFV). The mechanisms responsible for its pathogenesis remain largely unknown, although increased inflammation has been linked to worsened outcome. YFV targets the liver, where it primarily infects hepatocytes. We found that two RNA-sensing proteins, RIG-I and P...
Article
Full-text available
The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for the current COVID-19 pandemic. An unbalanced immune response, characterized by a weak production of type I interferons (IFN-Is) and an exacerbated release of proinflammatory cytokines, contributes to the severe forms of the disease. SARS-CoV-2 is genetically related...
Preprint
Hepatitis C virus (HCV) infection triggers Golgi fragmentation through the Golgi-resident protein immunity-related GTPase M (IRGM). Here, we report the role of NLRP3 and ASC, two inflammasome components, in the initial events leading to this fragmentation. We show that ASC resides at the Golgi with IRGM at homeostasis. Upon infection, ASC dissociat...
Preprint
Full-text available
Yellow fever virus (YFV) is a single-stranded RNA virus primarily targeting the liver. Severe YF cases are responsible for viral hemorrhagic fever, plausibly precipitated by excessive pro-inflammatory cytokine response, resulting in up to 50% fatality. Pathogen recognition receptors (PRRs), such as the ubiquitously expressed cytoplasmic RIG-I-like...
Article
INTRODUCTION The emergence of three lethal coronaviruses in <20 years and the urgency of the COVID-19 pandemic have prompted efforts to develop new therapeutic strategies, including by repurposing existing agents. After performing a comparative analysis of the three pathogenic human coronaviruses severe acute respiratory syndrome coronavirus 1 (SAR...
Article
The interferon (IFN) response, a major vertebrate defense mechanism against viral infections, is initiated by RIG-I-like receptor (RLR)-mediated recognition of viral replicative intermediates in the cytosol. RLR purification methods coupled to RNA sequencing have recently led to the characterization of viral nucleic acid features recognized by RLRs...
Article
The retinoic acid–inducible gene I (RIG-I)–like receptors (RLRs) RIG-I, MDA5, and LGP2 stimulate inflammatory and antiviral responses by sensing nonself RNA molecules produced during viral replication. Here, we investigated how LGP2 regulates the RIG-I– and MDA5-dependent induction of type I interferon (IFN) signaling and showed that LGP2 interacte...
Article
Full-text available
Zika virus (ZIKV) invades and persists in the central nervous system (CNS), causing severe neurological diseases. However the virus journey, from the bloodstream to tissues through a mature endothelium, remains unclear. Here, we show that ZIKV-infected monocytes represent suitable carriers for viral dissemination to the CNS using human primary mono...
Article
The Endoplasmic Reticulum (ER) is the site for Zika virus (ZIKV) replication and is central to the cytopathic effects observed in infected cells. ZIKV induces the formation of ER-derived large cytoplasmic vacuoles followed by “implosive” cell death. Little is known about the nature of the ER factors that regulate flavivirus replication. Atlastins (...
Preprint
Full-text available
Pattern recognition receptors (PRRs) protect against host invasion by detecting specific molecular patterns found in pathogens and initiating an immune response. While microbial-derived PRR ligands have been extensively characterized, the contribution and relevance of endogenous ligands to PRR activation during viral infection remain overlooked. In...
Article
Full-text available
Background: To be transmitted to vertebrate hosts via the saliva of their vectors, arthropod-borne viruses have to cross several barriers in the mosquito body, including the midgut infection and escape barriers. Yellow fever virus (YFV) belongs to the genus Flavivirus, which includes human viruses transmitted by Aedes mosquitoes, such as dengue an...
Article
Full-text available
The recent emergence and re-emergence of viral infections transmitted by vectors, such as the Zika virus (ZIKV) and Dengue virus (DENV), is a cause for international concern. These highly pathogenic arboviruses represent a serious health burden in tropical and subtropical areas of the world. Despite the high morbidity and mortality associated with...
Preprint
Full-text available
Background To be transmitted to vertebrate hosts via the saliva of their vectors, arthropod-borne viruses have to cross several barriers in the mosquito body, including the midgut infection and escape barriers. Yellow fever virus (YFV) belongs to the genus Flavivirus, which includes human viruses transmitted by Aedes mosquitoes, such as Dengue and...
Article
Full-text available
Flaviviruses, such as dengue (DENV), West Nile (WNV), yellow fever (YFV) and Zika (ZIKV) viruses, are mosquito-borne pathogens that present a major risk to global public health. To identify host factors that promote flavivirus replication, we performed a genome-wide gain-of-function cDNA screen for human genes that enhance the replication of flaviv...
Article
Full-text available
Hepatitis E virus (HEV) is responsible for large waterborne epidemics of hepatitis in endemic countries and is an emerging zoonotic pathogen worldwide. In endemic regions, HEV-1 or HEV-2 genotypes are frequently associated with fulminant hepatitis in pregnant women, while with zoonotic HEV (HEV-3 and HEV-4), chronic cases of hepatitis and severe ne...
Preprint
Full-text available
Hepatitis E virus (HEV) is responsible for large waterborne epidemics of hepatitis in endemic countries and is an emerging zoonotic pathogen worldwide. In endemic regions, HEV-1 or HEV-2 genotypes are frequently associated with fulminant hepatitis in pregnant women, while with zoonotic HEV (HEV-3 and HEV-4), chronic cases of hepatitis and severe ne...
Article
Full-text available
Plasmacytoid dendritic cells (pDCs) are specialized in the production of interferons (IFNs) in response to viral infections. The Flaviviridae family comprises enveloped RNA viruses such as Hepatitis C virus (HCV) and Dengue virus (DENV). Cell-free flaviviridae virions poorly stimulate pDCs to produce IFN. By contrast, cells infected with HCV and DE...
Article
Full-text available
The mosquito-borne Zika virus (ZIKV) belongs to the flavivirus genus of the Flaviviridae family. Contemporary epidemic strains of ZIKV are associated with congenital malformations in infants, including microcephaly, as well as Guillain-Barré syndrome in adults. A risk of human-to-human transmission of ZIKV is also well documented. A worldwide resea...
Article
Defective interfering (DI) genomes, or defective viral genomes (DVGs), are truncated viral genomes generated during replication of most viruses, including live viral vaccines. Among these, "panhandle" or copy-back (cb) and "hairpin" or snap-back (sb) DI genomes are generated during RNA virus replication. 5' cb/sb DI genomes are highly relevant for...
Article
Full-text available
The flavivirus genus comprises major human pathogens, such as Dengue (DENV) and Zika (ZIKV) viruses. RIG-I and MDA5 are key cytoplasmic pathogen recognition receptors that are implicated in detecting viral RNAs. Here, we show that RNAs that co-purified with RIG-I during DENV infection are immuno-stimulatory, whereas RNAs bound to MDA5 are not. An a...
Article
Full-text available
Despite Flaviviridae viruses display high incidence, morbidity and mortality rates, the development of specific antiviral drugs for each virus is unlikely. Cyclophilins, a family of host peptidyl-prolyl cis / trans isomerase (PPIase), play a pivotal role in the lifecycle of many viruses and therefore represent an attractive target for broad-spectru...
Article
Full-text available
Dengue virus (DENV) is a major human pathogen causing millions of infections yearly. Despite intensive investigations, a DENV receptor that directly participates in virus internalization has not yet been characterized. Here, we report that the phosphatidylserine receptor TIM-1 is an authentic DENV entry receptor that plays an active role in virus e...
Article
Full-text available
The cytopathic effects of Zika virus (ZIKV) are poorly characterized. Innate immunity controls ZIKV infection and disease in most infected patients through mechanisms that remain to be understood. Here, we studied the morphological cellular changes induced by ZIKV and addressed the role of interferon-induced transmembrane proteins (IFITM), a family...
Article
Full-text available
ZIKA virus (ZIKV) is an emerging pathogen responsible for neurological disorders and congenital microcephaly. However, the molecular basis for ZIKV neurotropism remains poorly understood. Here, we show that Axl is expressed in human microglia and astrocytes in the developing brain and that it mediates ZIKV infection of glial cells. Axl-mediated ZIK...
Article
Full-text available
Attenuated measles virus (MV) is currently being evaluated in clinical trials as an oncolytic therapeutic agent. Originally used for its lytic activity against tumor cells, it is now admitted that the effectiveness of MV also lies in its ability to initiate antitumor immune responses through the activation of dendritic cells (DCs). In this study, w...
Article
Full-text available
Unlabelled: The live attenuated yellow fever virus (YFV) vaccine 17D stands as a "gold standard" for a successful vaccine. 17D was developed empirically by passaging the wild-type Asibi strain in mouse and chicken embryo tissues. Despite its immense success, the molecular determinants for virulence attenuation and immunogenicity of the 17D vaccine...
Data
Transfection of dynamin-2 siRNA impairs transferrin receptor (CD71) internalization. HeLa cells were transfected with an siRNA pool to dynamin-2 (siDyn-2) or the nontargeting negative control (siNT). Cell surface expression of CD71 was assessed 72 h posttransfection by flow cytometry. Download
Data
The 17D vaccine infects human hepatocyte cell lines more efficiently than the parental strain Asibi. Huh7 or HepG2 cells were infected with YFV 17D or Asibi at an MOI of 1. Twenty-four hours after infection, the percentage of infected cells was assessed by flow cytometry using the 2D12 anti-YFV E protein MAb. Download
Data
siRNAs directed against the clathrin heavy chain and caveolin-1 do not impair 17D infection in several human cell lines. Cells of the HeLa, 293T, and Huh7.5 cell lines were transfected with an siRNA pool targeting clathrin heavy chain (siCHC) or caveolin-1 (siCav1) or the nontargeting negative control (siNT). (A) Silencing of CHC and caveolin-1 wer...
Data
Primers used for semiquantitative and real-time PCR.
Data
17D entry is not mediated by the clathrin-independent (CI) pathway that drives IL-2Rβ endocytosis. Download
Data
17D infection is independent of the IL-2Rβ clathrin-independent pathway. Hep2β cells were transfected with siRNA targeting the clathrin heavy chain (siCHC), ATP6V1β2 (siATPB6V1B2), Pak1, Rac1, or cortactin (siCTTN) or the nontargeting negative control (siNT). (A) Silencing was assessed by immunoblotting 72 h posttransfection. (B) Quantification of...
Data
E380 mutant Asibi RVPs are highly sensitive to CHC depletion. HeLa cells were transfected with an siRNA pool targeting the clathrin heavy chain (siCHC) or ATP6V1β2 or a nontargeting siRNA (siNT) as a negative control and then infected with the indicated RVPs 72 h posttransfection. Infection was assessed 24 h later by flow cytometry using the anti-Y...
Data
Effect of clathrin-mediated endocytosis inhibition on 17D and Asibi infection. HeLa cells were transfected with an siRNA pool to clathrin heavy chain (siCHC) or ATP6V1β2 (siATPB6V1B2) or the nontargeting negative control (siNT). (A) Silencing of CHC and ATP6V1β2 was assessed 72 h posttransfection by immunoblotting. (B) Cell surface expression of tr...
Article
Full-text available
Although plasmacytoid dendritic cells (pDCs) represent a rare immune cell type, they are the most important source of type I interferons (IFNs) upon viral infection. Phagocytosed RNA viruses and RNA virus-infected cells are detected by pDCs with the endosomal pattern recognition receptor (PRR) toll-like receptor 7 (TLR7). We showed that replication...
Article
The expression of hundreds of interferon-stimulated genes (ISGs) causes the cellular "antiviral state" in which the replication of many viruses, including HIV-1, is attenuated. We conducted a screen for ISGs that inhibit HIV-1 virion production and found that 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNP), a membrane-associated protein with unk...
Article
Full-text available
Proteins of the ESCRT (endosomal sorting complex required for transport) complex function in membrane fission processes, such as multivesicular body (MVBs) formation, the terminal stages of cytokinesis, and separation of enveloped viruses from the plasma membrane. In mammalian cells, the machinery consists of a network of more than 20 proteins, org...