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Le virus de la fièvre de la vallée du Rift (VFVR) est un agent pathogène transmis à l’homme et au bétail par la piqûre de moustiques. Ce virus, découvert au Kenya en 1930, est considéré par l’Organisation mondiale de la santé comme présentant un risque important de provoquer de vastes épidémies. Les moyens dédiés à la lutte contre le VFVR restent toutefois particulièrement limités et le virus est mal connu. Dans cette Synthèse, nous nous attacherons à présenter ce virus avant de nous intéresser plus spécifiquement à son facteur de virulence, la protéine NSs. Nous discuterons la capacité de cette protéine virale à former des fibrilles de type amyloïde et son implication dans la neurotoxicité du virus chez les animaux infectés.
Psylvia Léger; Pierre-Yves Lozach. Le virus de la fièvre de la vallée du Rift et son étonnante protéine NSs. médecine/sciences 2021, 37, 601 -608.
AMA StylePsylvia Léger, Pierre-Yves Lozach. Le virus de la fièvre de la vallée du Rift et son étonnante protéine NSs. médecine/sciences. 2021; 37 (6-7):601-608.
Chicago/Turabian StylePsylvia Léger; Pierre-Yves Lozach. 2021. "Le virus de la fièvre de la vallée du Rift et son étonnante protéine NSs." médecine/sciences 37, no. 6-7: 601-608.
SARS-CoV-2 is a newly emerged coronavirus that caused the global COVID-19 outbreak in early 2020. COVID-19 is primarily associated with lung injury, but many other clinical symptoms such as loss of smell and taste demonstrated broad tissue tropism of the virus. Early SARS-CoV-2-host cell interactions and entry mechanisms remain poorly understood. Investigating SARS-CoV-2 infection in tissue culture, we found that the protease TMPRSS2 determines the entry pathway used by the virus. In the presence of TMPRSS2, the proteolytic process of SARS-CoV-2 was completed at the plasma membrane, and the virus rapidly entered the cells within 10 min in a pH-independent manner. When target cells lacked TMPRSS2 expression, the virus was endocytosed and sorted into endolysosomes, from which SARS-CoV-2 entered the cytosol via acid-activated cathepsin L protease 40-60 min post infection. Overexpression of TMPRSS2 in non-TMPRSS2 expressing cells abolished the dependence of infection on the cathepsin L pathway and restored sensitivity to the TMPRSS2 inhibitors. Together, our results indicate that SARS-CoV-2 infects cells through distinct, mutually exclusive entry routes and highlight the importance of TMPRSS2 for SARS-CoV-2 sorting into either pathway.
Jana Koch; Zina M Uckeley; Patricio Doldan; Megan Stanifer; Steeve Boulant; Pierre‐Yves Lozach. TMPRSS2 expression dictates the entry route used by SARS‐CoV‐2 to infect host cells. The EMBO Journal 2021, e107821 .
AMA StyleJana Koch, Zina M Uckeley, Patricio Doldan, Megan Stanifer, Steeve Boulant, Pierre‐Yves Lozach. TMPRSS2 expression dictates the entry route used by SARS‐CoV‐2 to infect host cells. The EMBO Journal. 2021; ():e107821.
Chicago/Turabian StyleJana Koch; Zina M Uckeley; Patricio Doldan; Megan Stanifer; Steeve Boulant; Pierre‐Yves Lozach. 2021. "TMPRSS2 expression dictates the entry route used by SARS‐CoV‐2 to infect host cells." The EMBO Journal , no. : e107821.
With over 80 members worldwide, Orthobunyavirus is the largest genus in the Peribunyaviridae family. Orthobunyaviruses (OBVs) are arthropod-borne viruses that are structurally simple, with a trisegmented, negative-sense RNA genome and only four structural proteins. OBVs are potential agents of emerging and re-emerging diseases and overall represent a global threat to both public and veterinary health. The focus of this review is on the very first steps of OBV infection in mammalian hosts, from virus binding to penetration and release of the viral genome into the cytosol. Here, we address the most current knowledge and advances regarding OBV receptors, endocytosis, and fusion.
Stefan Windhaber; Qilin Xin; Pierre-Yves Lozach. Orthobunyaviruses: From Virus Binding to Penetration into Mammalian Host Cells. Viruses 2021, 13, 872 .
AMA StyleStefan Windhaber, Qilin Xin, Pierre-Yves Lozach. Orthobunyaviruses: From Virus Binding to Penetration into Mammalian Host Cells. Viruses. 2021; 13 (5):872.
Chicago/Turabian StyleStefan Windhaber; Qilin Xin; Pierre-Yves Lozach. 2021. "Orthobunyaviruses: From Virus Binding to Penetration into Mammalian Host Cells." Viruses 13, no. 5: 872.
Phenuiviridae is a large family of arthropod-borne viruses with over 100 species worldwide. Several cause severe diseases in both humans and livestock. Global warming and the apparent geographical expansion of arthropod vectors are good reasons to seriously consider these viruses potential agents of emerging diseases. With an increasing frequency and number of epidemics, some phenuiviruses represent a global threat to public and veterinary health. This review focuses on the early stage of phenuivirus infection in mammalian host cells. We address current knowledge on each step of the cell entry process, from virus binding to penetration into the cytosol. Virus receptors, endocytosis, and fusion mechanisms are discussed in light of the most recent progress on the entry of banda-, phlebo-, and uukuviruses, which together constitute the three prominent genera in the Phenuiviridae family.
Jana Koch; Qilin Xin; Nicole Tischler; Pierre-Yves Lozach. Entry of Phenuiviruses into Mammalian Host Cells. Viruses 2021, 13, 299 .
AMA StyleJana Koch, Qilin Xin, Nicole Tischler, Pierre-Yves Lozach. Entry of Phenuiviruses into Mammalian Host Cells. Viruses. 2021; 13 (2):299.
Chicago/Turabian StyleJana Koch; Qilin Xin; Nicole Tischler; Pierre-Yves Lozach. 2021. "Entry of Phenuiviruses into Mammalian Host Cells." Viruses 13, no. 2: 299.
SARS-CoV-2 is a newly emerged coronavirus (CoV) that spread through human populations worldwide in early 2020. CoVs rely on host cell proteases for activation and infection. The trypsin-like protease TMPRSS2 at the cell surface, cathepsin L in endolysosomes, and furin in the Golgi have all been implicated in the SARS-CoV-2 proteolytic processing. Whether SARS-CoV-2 depends on endocytosis internalization and vacuolar acidification for infectious entry remains unclear. Here, we examined the dynamics of SARS-CoV-2 activation during the cell entry process in tissue culture. Using four cell lines representative of lung, colon, and kidney epithelial tissues, we found that TMPRSS2 determines the SARS-CoV-2 entry pathways. In TMPRSS2-positive cells, infection was sensitive to aprotinin, a TMPRSS2 inhibitor, but not to SB412515, a drug that impairs cathepsin L. Infectious penetration was marginally dependent on endosomal acidification, and the virus passed the protease-sensitive step within 10 min. In a marked contrast, in TMPRSS2-negative cells cathepsin L and low pH were required for SARS-CoV-2 entry. The cathepsin L-activated penetration occurred within 40-60 min after internalization and required intact endolysosomal functions. Importantly, pre-activation of the virus allowed it to bypass the need for endosomal acidification for viral fusion and productive entry. Overall, our results indicate that SARS-CoV-2 shares with other CoVs a strategy of differential use of host cell proteases for activation and infectious penetration. This study also highlights the importance of TMPRSS2 in dictating the entry pathway used by SARS-CoV-2.SignificancePreventing SARS-CoV-2 spread requires approaches affecting early virus-host cell interactions before the virus enters and infects target cells. Host cell proteases are critical for coronavirus activation and infectious entry. Here, we reconcile apparent contradictory observations from recent reports on endosomal acidification and the role of furin, TMPRSS2, and cathepsin L in the productive entry and fusion process of SARS-CoV-2. Investigating authentic virus in various cell types, we demonstrated that SARS-CoV-2 developed the ability to use different entry pathways, depending on the proteases expressed by the target cell. Our results have strong implications for future research on the apparent broad tropism of the virus in vivo. This study also provides a handle to develop novel antiviral strategies aiming to block virus entry, as illustrated with the several drugs that we identified to prevent SARS-CoV-2 infection, some with low IC50.
Jana Koch; Zina M Uckeley; Patricio Doldan; Megan Stanifer; Steeve Boulant; Pierre-Yves Lozach. Host Cell Proteases Drive Early or Late SARS-CoV-2 Penetration. 2020, 1 .
AMA StyleJana Koch, Zina M Uckeley, Patricio Doldan, Megan Stanifer, Steeve Boulant, Pierre-Yves Lozach. Host Cell Proteases Drive Early or Late SARS-CoV-2 Penetration. . 2020; ():1.
Chicago/Turabian StyleJana Koch; Zina M Uckeley; Patricio Doldan; Megan Stanifer; Steeve Boulant; Pierre-Yves Lozach. 2020. "Host Cell Proteases Drive Early or Late SARS-CoV-2 Penetration." , no. : 1.
Viruses exhibit an elegant simplicity, as they are so basic, but so frightening. Although only a few are life threatening, they have substantial implications for human health and the economy, as exemplified by the ongoing coronavirus pandemic. Viruses are rather small infectious agents found in all types of life forms, from animals and plants to prokaryotes and archaebacteria. They are obligate intracellular parasites, and as such, subvert many molecular and cellular processes of the host cell to ensure their own replication, amplification, and subsequent spread. This special issue addresses the cell biology of viral infections based on a collection of original research articles, communications, opinions, and reviews on various aspects of virus-host cell interactions. Together, these articles not only provide a glance into the latest research on the cell biology of viral infections, but also include novel technological developments.
Pierre-Yves Lozach. Cell Biology of Viral Infections. Cells 2020, 9, 2431 .
AMA StylePierre-Yves Lozach. Cell Biology of Viral Infections. Cells. 2020; 9 (11):2431.
Chicago/Turabian StylePierre-Yves Lozach. 2020. "Cell Biology of Viral Infections." Cells 9, no. 11: 2431.
Amyloid fibrils result from the aggregation of host cell-encoded proteins, many giving rise to specific human illnesses such as Alzheimer's disease. Here we show that the major virulence factor of Rift Valley fever virus, the protein NSs, forms filamentous structures in the brain of mice and affects mortality. NSs assembles into nuclear and cytosolic disulfide bond-dependent fibrillary aggregates in infected cells. NSs structural arrangements exhibit characteristics typical for amyloids, such as an ultrastructure of 12 nm-width fibrils, a strong detergent resistance, and interactions with the amyloid-binding dye Thioflavin-S. The assembly dynamics of viral amyloid-like fibrils can be visualized in real-time. They form spontaneously and grow in an amyloid fashion within 5 hours. Together, our results demonstrate that viruses can encode amyloid-like fibril-forming proteins and have strong implications for future research on amyloid aggregation and toxicity in general.
Psylvia Léger; Eliana Nachman; Karsten Richter; Carole Tamietti; Jana Koch; Robin Burk; Susann Kummer; Qilin Xin; Megan Stanifer; Michèle Bouloy; Steeve Boulant; Hans-Georg Kräusslich; Xavier Montagutelli; Marie Flamand; Carmen Nussbaum-Krammer; Pierre-Yves Lozach. NSs amyloid formation is associated with the virulence of Rift Valley fever virus in mice. Nature Communications 2020, 11, 1 -19.
AMA StylePsylvia Léger, Eliana Nachman, Karsten Richter, Carole Tamietti, Jana Koch, Robin Burk, Susann Kummer, Qilin Xin, Megan Stanifer, Michèle Bouloy, Steeve Boulant, Hans-Georg Kräusslich, Xavier Montagutelli, Marie Flamand, Carmen Nussbaum-Krammer, Pierre-Yves Lozach. NSs amyloid formation is associated with the virulence of Rift Valley fever virus in mice. Nature Communications. 2020; 11 (1):1-19.
Chicago/Turabian StylePsylvia Léger; Eliana Nachman; Karsten Richter; Carole Tamietti; Jana Koch; Robin Burk; Susann Kummer; Qilin Xin; Megan Stanifer; Michèle Bouloy; Steeve Boulant; Hans-Georg Kräusslich; Xavier Montagutelli; Marie Flamand; Carmen Nussbaum-Krammer; Pierre-Yves Lozach. 2020. "NSs amyloid formation is associated with the virulence of Rift Valley fever virus in mice." Nature Communications 11, no. 1: 1-19.
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 (rTOSVɸNSs). Unlike rTOSV and the wt virus, rTOSVɸNSs was unable to (i) suppress interferon (IFN)-b messenger RNA induction; and (ii) grow efficiently in cells producing IFN-b. Together, our results highlight the importance of NSs for TOSV in evading the IFN response and provide a comprehensive toolbox to investigate the TOSV life cycle in mammalian and insect host cells, including several novel polyclonal antibodies.
Franziska Woelfl; Psylvia Léger; Nadia Oreshkova; Felix Pahmeier; Stefan Windhaber; Jana Koch; Megan Stanifer; Gleyder Roman Sosa; Zina M. Uckeley; Felix A. Rey; Steeve Boulant; Jeroen Kortekaas; Paul J. Wichgers Schreur; Pierre-Yves Lozach. Novel Toscana Virus Reverse Genetics System Establishes NSs as an Antagonist of Type I Interferon Responses. Viruses 2020, 12, 400 .
AMA StyleFranziska Woelfl, Psylvia Léger, Nadia Oreshkova, Felix Pahmeier, Stefan Windhaber, Jana Koch, Megan Stanifer, Gleyder Roman Sosa, Zina M. Uckeley, Felix A. Rey, Steeve Boulant, Jeroen Kortekaas, Paul J. Wichgers Schreur, Pierre-Yves Lozach. Novel Toscana Virus Reverse Genetics System Establishes NSs as an Antagonist of Type I Interferon Responses. Viruses. 2020; 12 (4):400.
Chicago/Turabian StyleFranziska Woelfl; Psylvia Léger; Nadia Oreshkova; Felix Pahmeier; Stefan Windhaber; Jana Koch; Megan Stanifer; Gleyder Roman Sosa; Zina M. Uckeley; Felix A. Rey; Steeve Boulant; Jeroen Kortekaas; Paul J. Wichgers Schreur; Pierre-Yves Lozach. 2020. "Novel Toscana Virus Reverse Genetics System Establishes NSs as an Antagonist of Type I Interferon Responses." Viruses 12, no. 4: 400.
Severe fever with thrombocytopenia syndrome (SFTS) virus (SFTSV) is an emerging tick-borne virus that carries a high fatality rate of 12%-50%. In-depth understanding of the SFTSV-induced pathogenesis mechanism is critical for developing effective anti-SFTS therapeutics. Here, we report transcriptomic analysis of blood samples from SFTS patients. We observe a strong correlation between inflammatory responses and disease progression and fatal outcome. Quantitative proteomic analysis of SFTSV infection confirms the induction of inflammation and further reveals virus-induced mitochondrial dysfunction. Mechanistically, SFTSV infection triggers BCL2 antagonist/killer 1 (BAK) upregulation and BAK/BCL2-associated X (BAX) activation, leading to mitochondrial DNA (mtDNA) oxidization and subsequent cytosolic release. The cytosolic mtDNA binds and triggers NLRP3 inflammasome activation. Notably, the BAK expression level correlates with SFTS disease progression and fatal outcome. These findings provide insights into the clinical features and molecular underpinnings of severe SFTS, which may aid in patient care and therapeutic design, and may also be conserved during infection by other highly pathogenic viruses.
Shufen Li; Hao Li; Yu-Lan Zhang; Qi-Lin Xin; Zhen-Qiong Guan; Xi Chen; Xiao-Ai Zhang; Xiao-Kun Li; Geng-Fu Xiao; Pierre-Yves Lozach; Jun Cui; Wei Liu; Lei-Ke Zhang; Ke Peng. SFTSV Infection Induces BAK/BAX-Dependent Mitochondrial DNA Release to Trigger NLRP3 Inflammasome Activation. Cell Reports 2020, 30, 4370 -4385.e7.
AMA StyleShufen Li, Hao Li, Yu-Lan Zhang, Qi-Lin Xin, Zhen-Qiong Guan, Xi Chen, Xiao-Ai Zhang, Xiao-Kun Li, Geng-Fu Xiao, Pierre-Yves Lozach, Jun Cui, Wei Liu, Lei-Ke Zhang, Ke Peng. SFTSV Infection Induces BAK/BAX-Dependent Mitochondrial DNA Release to Trigger NLRP3 Inflammasome Activation. Cell Reports. 2020; 30 (13):4370-4385.e7.
Chicago/Turabian StyleShufen Li; Hao Li; Yu-Lan Zhang; Qi-Lin Xin; Zhen-Qiong Guan; Xi Chen; Xiao-Ai Zhang; Xiao-Kun Li; Geng-Fu Xiao; Pierre-Yves Lozach; Jun Cui; Wei Liu; Lei-Ke Zhang; Ke Peng. 2020. "SFTSV Infection Induces BAK/BAX-Dependent Mitochondrial DNA Release to Trigger NLRP3 Inflammasome Activation." Cell Reports 30, no. 13: 4370-4385.e7.
Novel tick-borne phleboviruses in the Phenuiviridae family, which are highly pathogenic in humans and all closely related to Uukuniemi virus (UUKV), have recently emerged on different continents. How phleboviruses assemble, bud, and exit cells remains largely elusive. Here, we performed high-resolution, label-free mass spectrometry analysis of UUKV immunoprecipitated from cell lysates and identified 39 cellular partners interacting with the viral envelope glycoproteins. The importance of these host factors for UUKV infection was validated by silencing each host factor by RNA interference. This revealed Golgi-specific brefeldin A-resistance guanine nucleotide exchange factor 1 (GBF1), a guanine nucleotide exchange factor resident in the Golgi, as a critical host factor required for the UUKV life cycle. An inhibitor of GBF1, Golgicide A, confirmed the role of the cellular factor in UUKV infection. We could pinpoint the GBF1 requirement to UUKV replication and particle assembly. When the investigation was extended to viruses from various positive and negative RNA viral families, we found that not only phleboviruses rely on GBF1 for infection, but also Flavi-, Corona-, Rhabdo-, and Togaviridae. In contrast, silencing or blocking GBF1 did not abrogate infection by the human adenovirus serotype 5 and immunodeficiency retrovirus type 1, the replication of both requires nuclear steps. Together our results indicate that UUKV relies on GBF1 for viral replication, assembly and egress. This study also highlights the proviral activity of GBF1 in the infection by a broad range of important zoonotic RNA viruses. Graphical Abstract Highlights Quantitative proteomics reveals GBF1 to interact with Uukuniemi virus glycoproteins. GBF1 is a proviral host factor for phleboviruses and other zoonotic RNA viruses. GBF1 supports phlebovirus replication and assembly and release of particles. The GBF1 inhibitor Golgicide A blocks infection with zoonotic RNA viruses.
Zina M. Uckeley; Rebecca Moeller; Lars I. Kühn; Emma Nilsson; Claudia Robens; Lisa Lasswitz; Richard Lindqvist; AnnaSara Lenman; Vania Passos; Yannik Voss; Christian Sommerauer; Martin Kampmann; Christine Goffinet; Felix Meissner; Anna K. Överby; Pierre-Yves Lozach; Gisa Gerold. Quantitative Proteomics of Uukuniemi Virus-host Cell Interactions Reveals GBF1 as Proviral Host Factor for Phleboviruses. Molecular & Cellular Proteomics 2019, 18, 2401 -2417.
AMA StyleZina M. Uckeley, Rebecca Moeller, Lars I. Kühn, Emma Nilsson, Claudia Robens, Lisa Lasswitz, Richard Lindqvist, AnnaSara Lenman, Vania Passos, Yannik Voss, Christian Sommerauer, Martin Kampmann, Christine Goffinet, Felix Meissner, Anna K. Överby, Pierre-Yves Lozach, Gisa Gerold. Quantitative Proteomics of Uukuniemi Virus-host Cell Interactions Reveals GBF1 as Proviral Host Factor for Phleboviruses. Molecular & Cellular Proteomics. 2019; 18 (12):2401-2417.
Chicago/Turabian StyleZina M. Uckeley; Rebecca Moeller; Lars I. Kühn; Emma Nilsson; Claudia Robens; Lisa Lasswitz; Richard Lindqvist; AnnaSara Lenman; Vania Passos; Yannik Voss; Christian Sommerauer; Martin Kampmann; Christine Goffinet; Felix Meissner; Anna K. Överby; Pierre-Yves Lozach; Gisa Gerold. 2019. "Quantitative Proteomics of Uukuniemi Virus-host Cell Interactions Reveals GBF1 as Proviral Host Factor for Phleboviruses." Molecular & Cellular Proteomics 18, no. 12: 2401-2417.
Rift Valley fever virus (RVFV) is a mosquito-borne phlebovirus that represents as a serious health threat to both domestic animals and humans. The viral protein NSs is the key virulence factor of RVFV, and has been proposed that NSs nuclear filament formation is critical for its virulence. However, the detailed mechanisms are currently unclear. Here, we generated a T7 RNA polymerase-driven RVFV reverse genetics system based on a strain imported into China (BJ01). Several NSs mutations (T1, T3 and T4) were introduced into the system for investigating the correlation between NSs filament formation and virulence in vivo. The NSs T1 mutant showed distinct NSs filament in the nuclei of infected cells, the T3 mutant diffusively localized in the cytoplasm and the T4 mutant showed fragmented nuclear filament formation. Infection of BALB/c mice with these NSs mutant viruses revealed that the in vivo virulence was severely compromised for all three NSs mutants, including the T1 mutant. This suggests that NSs filament formation is not directly correlated with RVFV virulence in vivo. Results from this study not only shed new light on the virulence mechanism of RVFV NSs but also provided tools for future in-depth investigations of RVFV pathogenesis and anti-RVFV drug screening.
Shufen Li; Xiangtao Zhu; Zhenqiong Guan; Wenfeng Huang; Yulan Zhang; Jeroen Kortekaas; Pierre-Yves Lozach; Ke Peng. NSs Filament Formation Is Important but Not Sufficient for RVFV Virulence In Vivo. Viruses 2019, 11, 834 .
AMA StyleShufen Li, Xiangtao Zhu, Zhenqiong Guan, Wenfeng Huang, Yulan Zhang, Jeroen Kortekaas, Pierre-Yves Lozach, Ke Peng. NSs Filament Formation Is Important but Not Sufficient for RVFV Virulence In Vivo. Viruses. 2019; 11 (9):834.
Chicago/Turabian StyleShufen Li; Xiangtao Zhu; Zhenqiong Guan; Wenfeng Huang; Yulan Zhang; Jeroen Kortekaas; Pierre-Yves Lozach; Ke Peng. 2019. "NSs Filament Formation Is Important but Not Sufficient for RVFV Virulence In Vivo." Viruses 11, no. 9: 834.
Zina M. Uckeley; Jana Koch; Nicole Tischler; Psylvia Léger; Pierre-Yves Lozach. Cell biology of phlebovirus entry. Virologie 2019, 23, 176 -187.
AMA StyleZina M. Uckeley, Jana Koch, Nicole Tischler, Psylvia Léger, Pierre-Yves Lozach. Cell biology of phlebovirus entry. Virologie. 2019; 23 (3):176-187.
Chicago/Turabian StyleZina M. Uckeley; Jana Koch; Nicole Tischler; Psylvia Léger; Pierre-Yves Lozach. 2019. "Cell biology of phlebovirus entry." Virologie 23, no. 3: 176-187.
To infect host cells, viruses have to gain access to the intracellular compartment. The infection process starts with the attachment of viruses to the cell surface. Then a complex series of events, highly dynamic, tightly intricate, and often hard to investigate, follows. This includes virus displacement at the plasma membrane, binding to receptors, signaling, internalization, and release of the viral genome and material into the cytosol. In the past decades, the emergence of sensitive, accurate fluorescence-based technologies has opened new perspectives of investigations in the field. Visualization of single viral particles in fixed and living cells as well as quantification of each virus entry step has been made possible. Here we describe the procedure to fluorescently label viral particles. We also illustrate how to use this powerful tool to decipher the entry of viruses with the most recent fluorescence-based techniques such as high-speed confocal and total internal reflection microscopy, flow cytometry, and fluorimetry.
Anja B. Hoffmann; Magalie Mazelier; Psylvia Léger; Pierre-Yves Lozach. Deciphering Virus Entry with Fluorescently Labeled Viral Particles. Advanced Structural Safety Studies 2018, 159 -183.
AMA StyleAnja B. Hoffmann, Magalie Mazelier, Psylvia Léger, Pierre-Yves Lozach. Deciphering Virus Entry with Fluorescently Labeled Viral Particles. Advanced Structural Safety Studies. 2018; ():159-183.
Chicago/Turabian StyleAnja B. Hoffmann; Magalie Mazelier; Psylvia Léger; Pierre-Yves Lozach. 2018. "Deciphering Virus Entry with Fluorescently Labeled Viral Particles." Advanced Structural Safety Studies , no. : 159-183.
Pierre-Yves Lozach. Early Virus–Host Cell Interactions. Journal of Molecular Biology 2018, 430, 2555 -2556.
AMA StylePierre-Yves Lozach. Early Virus–Host Cell Interactions. Journal of Molecular Biology. 2018; 430 (17):2555-2556.
Chicago/Turabian StylePierre-Yves Lozach. 2018. "Early Virus–Host Cell Interactions." Journal of Molecular Biology 430, no. 17: 2555-2556.
Pierre-Yves Lozach. LOEWE Workshop Particle Characterization in Medicine and Biology. Pharmaceutical Frontiers 2018, 1 .
AMA StylePierre-Yves Lozach. LOEWE Workshop Particle Characterization in Medicine and Biology. Pharmaceutical Frontiers. 2018; ():1.
Chicago/Turabian StylePierre-Yves Lozach. 2018. "LOEWE Workshop Particle Characterization in Medicine and Biology." Pharmaceutical Frontiers , no. : 1.
In the last decade, novel tick-borne pathogenic phleboviruses in the family Bunyaviridae , all closely related to Uukuniemi virus (UUKV), have emerged on different continents. To reproduce the tick-mammal switch in vitro , we first established a reverse genetics system to rescue UUKV with a genome close to that of the authentic virus isolated from the Ixodes ricinus tick reservoir. The IRE/CTVM19 and IRE/CTVM20 cell lines, both derived from I. ricinus , were susceptible to the virus rescued from plasmid DNAs and supported production of the virus over many weeks, indicating that infection was persistent. The glycoprotein G C was mainly highly mannosylated on tick cell-derived viral progeny. The second envelope viral protein, G N , carried mostly N -glycans not recognized by the classical glycosidases peptide- N -glycosidase F (PNGase F) and endoglycosidase H (Endo H). Treatment with β-mercaptoethanol did not impact the apparent molecular weight of G N . On viruses originating from mammalian BHK-21 cells, G N glycosylations were exclusively sensitive to PNGase F, and the electrophoretic mobility of the protein was substantially slower after the reduction of disulfide bonds. Furthermore, the amount of viral nucleoprotein per focus forming unit differed markedly whether viruses were produced in tick or BHK-21 cells, suggesting a higher infectivity for tick cell-derived viruses. Together, our results indicate that UUKV particles derived from vector tick cells have glycosylation and structural specificities that may influence the initial infection in mammalian hosts. This study also highlights the importance of working with viruses originating from arthropod vector cells in investigations of the cell biology of arbovirus transmission and entry into mammalian hosts. IMPORTANCE Tick-borne phleboviruses represent a growing threat to humans globally. Although ticks are important vectors of infectious emerging diseases, previous studies have mainly involved virus stocks produced in mammalian cells. This limitation tends to minimize the importance of host alternation in virus transmission to humans and initial infection at the molecular level. With this study, we have developed an in vitro tick cell-based model that allows production of the tick-borne Uukuniemi virus to high titers. Using this system, we found that virions derived from tick cells have specific structural properties and N -glycans that may enhance virus infectivity for mammalian cells. By shedding light on molecular aspects of tick-derived viral particles, our data illustrate the importance of considering the host switch in studying early virus-mammalian receptor/cell interactions. The information gained here lays the basis for future research on not only tick-borne phleboviruses but also all viruses and other pathogens transmitted by ticks.
Magalie Mazelier; Ronan Rouxel; Michael Zumstein; Roberta Mancini; Lesley Bell-Sakyi; Pierre-Yves Lozach. Uukuniemi Virus as a Tick-Borne Virus Model. Journal of Virology 2016, 90, 6784 -6798.
AMA StyleMagalie Mazelier, Ronan Rouxel, Michael Zumstein, Roberta Mancini, Lesley Bell-Sakyi, Pierre-Yves Lozach. Uukuniemi Virus as a Tick-Borne Virus Model. Journal of Virology. 2016; 90 (15):6784-6798.
Chicago/Turabian StyleMagalie Mazelier; Ronan Rouxel; Michael Zumstein; Roberta Mancini; Lesley Bell-Sakyi; Pierre-Yves Lozach. 2016. "Uukuniemi Virus as a Tick-Borne Virus Model." Journal of Virology 90, no. 15: 6784-6798.
The Bunyaviridae is the largest family of RNA viruses, with over 350 members worldwide. Several of these viruses cause severe diseases in livestock and humans. With an increasing number and frequency of outbreaks, bunyaviruses represent a growing threat to public health and agricultural productivity globally. Yet, the receptors, cellular factors and endocytic pathways used by these emerging pathogens to infect cells remain largely uncharacterized. The focus of this review is on the early steps of bunyavirus infection, from virus binding to penetration from endosomes. We address current knowledge and advances for members from each genus in the Bunyaviridae family regarding virus receptors, uptake, intracellular trafficking and fusion.
Amelina Albornoz; Anja B. Hoffmann; Pierre-Yves Lozach; Nicole D. Tischler. Early Bunyavirus-Host Cell Interactions. Viruses 2016, 8, 143 .
AMA StyleAmelina Albornoz, Anja B. Hoffmann, Pierre-Yves Lozach, Nicole D. Tischler. Early Bunyavirus-Host Cell Interactions. Viruses. 2016; 8 (5):143.
Chicago/Turabian StyleAmelina Albornoz; Anja B. Hoffmann; Pierre-Yves Lozach; Nicole D. Tischler. 2016. "Early Bunyavirus-Host Cell Interactions." Viruses 8, no. 5: 143.
Bunyaviruses represent a growing threat to humans and livestock globally. The receptors, cellular factors, and endocytic pathways used by these emerging pathogens to infect cells remain largely unidentified and poorly characterized. DC-SIGN is a C-type lectin highly expressed on dermal dendritic cells that has been found to act as an authentic entry receptor for many phleboviruses (Bunyaviridae), including Rift Valley fever virus (RVFV), Toscana virus (TOSV), and Uukuniemi virus (UUKV). We found that these phleboviruses can exploit another C-type lectin, L-SIGN, for infection. L-SIGN shares 77% sequence homology with DC-SIGN and is expressed on liver sinusoidal endothelial cells. L-SIGN is required for UUKV binding but not for virus internalization. An endocytosis-defective mutant of L-SIGN was still able to mediate virus uptake and infection, indicating that L-SIGN acts as an attachment receptor for phleboviruses rather than an endocytic receptor. Our results point out a fundamental difference in the use of the C-type lectins L-SIGN and DC-SIGN by UUKV to enter cells, though both proteins are closely related in terms of molecular structure and biological function. This study sheds new light on the molecular mechanisms by which phleboviruses target the liver and also highlights the added complexity in virus-receptor interactions beyond attachment.
Psylvia Léger; Marilou Tetard; Berthe Youness; Nicole Cordes; Ronan Rouxel; Marie Flamand; Pierre-Yves Lozach. Differential Use of the C-Type Lectins L-SIGN and DC-SIGN for Phlebovirus Endocytosis. Traffic 2016, 17, 639 -656.
AMA StylePsylvia Léger, Marilou Tetard, Berthe Youness, Nicole Cordes, Ronan Rouxel, Marie Flamand, Pierre-Yves Lozach. Differential Use of the C-Type Lectins L-SIGN and DC-SIGN for Phlebovirus Endocytosis. Traffic. 2016; 17 (6):639-656.
Chicago/Turabian StylePsylvia Léger; Marilou Tetard; Berthe Youness; Nicole Cordes; Ronan Rouxel; Marie Flamand; Pierre-Yves Lozach. 2016. "Differential Use of the C-Type Lectins L-SIGN and DC-SIGN for Phlebovirus Endocytosis." Traffic 17, no. 6: 639-656.
The hantavirus membrane fusion process is mediated by the Gc envelope glycoprotein from within endosomes. Yet, little is known about the specific mechanism that triggers Gc fusion activation and its pre- and post-fusion conformations. We established cell-free in vitro systems to characterize hantavirus fusion activation. Low pH was sufficient to trigger the interaction of virus-like particles (VLPs) with liposomes. This interaction was dependent on a pre-fusion glycoprotein arrangement. Further, low pH induced Gc multimerization changes leading to non-reversible Gc homotrimers. These trimers were resistant to detergent, heat and protease digestion, suggesting characteristics of a stable post-fusion structure. No acid-dependent oligomerization rearrangement was detected for the trypsin-sensitive Gn envelope glycoprotein. Finally, acidification induced fusion of glycoprotein-expressing effector cells with non-susceptible CHO cells. Together, the data provide novel information on the Gc fusion trigger and its non-reversible activation involving lipid interaction, multimerization changes and membrane fusion which ultimately allow hantavirus entry into cells.
Rodrigo Acuña; Eduardo A. Bignon; Roberta Mancini; Pierre-Yves Lozach; Nicole D. Tischler. Acidification triggers Andes hantavirus membrane fusion and rearrangement of Gc into a stable post-fusion homotrimer. Journal of General Virology 2015, 96, 3192 -3197.
AMA StyleRodrigo Acuña, Eduardo A. Bignon, Roberta Mancini, Pierre-Yves Lozach, Nicole D. Tischler. Acidification triggers Andes hantavirus membrane fusion and rearrangement of Gc into a stable post-fusion homotrimer. Journal of General Virology. 2015; 96 (11):3192-3197.
Chicago/Turabian StyleRodrigo Acuña; Eduardo A. Bignon; Roberta Mancini; Pierre-Yves Lozach; Nicole D. Tischler. 2015. "Acidification triggers Andes hantavirus membrane fusion and rearrangement of Gc into a stable post-fusion homotrimer." Journal of General Virology 96, no. 11: 3192-3197.
The Bunyaviridae constitute a large family of animal RNA viruses distributed worldwide, most members of which are transmitted to vertebrate hosts by arthropods and can cause severe pathologies in humans and livestock. With an increasing number of outbreaks, arthropod-borne bunyaviruses (arbo-bunyaviruses) present a global threat to public health and agricultural productivity. Yet transmission, tropism, receptors and cell entry remain poorly characterized. The focus of this review is on the initial infection of mammalian hosts by arbo-bunyaviruses from cellular and molecular perspectives, with particular attention to the human host. We address current knowledge and advances regarding the identity of the first-target cells and the subsequent processes of entry and penetration into the cytosol. Aspects of the vector-to-host switch that influence the early steps of cell infection in mammalian skin, where incoming particles are introduced by infected arthropods, are also highlighted and discussed.
Psylvia Léger; Pierre-Yves Lozach. Bunyaviruses: from transmission by arthropods to virus entry into the mammalian host first-target cells. Future Virology 2015, 10, 859 -881.
AMA StylePsylvia Léger, Pierre-Yves Lozach. Bunyaviruses: from transmission by arthropods to virus entry into the mammalian host first-target cells. Future Virology. 2015; 10 (7):859-881.
Chicago/Turabian StylePsylvia Léger; Pierre-Yves Lozach. 2015. "Bunyaviruses: from transmission by arthropods to virus entry into the mammalian host first-target cells." Future Virology 10, no. 7: 859-881.