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Adenovirus vector-based genetic vaccines have emerged as a powerful strategy against the SARS-CoV-2 health crisis. This success is not unexpected because adenoviruses combine many desirable features of a genetic vaccine. They are highly immunogenic and have a low and well characterized pathogenic profile paired with technological approachability. Ongoing efforts to improve adenovirus-vaccine vectors include the use of rare serotypes and non-human adenoviruses. In this review, we focus on the viral capsid and how the choice of genotypes influences the uptake and subsequent subcellular sorting. We describe how understanding capsid properties, such as stability during the entry process, can change the fate of the entering particles and how this translates into differences in immunity outcomes. We discuss in detail how mutating the membrane lytic capsid protein VI affects species C viruses’ post-entry sorting and briefly discuss if such approaches could have a wider implication in vaccine and/or vector development.
Coralie Daussy; Noémie Pied; Harald Wodrich. Understanding Post Entry Sorting of Adenovirus Capsids; A Chance to Change Vaccine Vector Properties. Viruses 2021, 13, 1221 .
AMA StyleCoralie Daussy, Noémie Pied, Harald Wodrich. Understanding Post Entry Sorting of Adenovirus Capsids; A Chance to Change Vaccine Vector Properties. Viruses. 2021; 13 (7):1221.
Chicago/Turabian StyleCoralie Daussy; Noémie Pied; Harald Wodrich. 2021. "Understanding Post Entry Sorting of Adenovirus Capsids; A Chance to Change Vaccine Vector Properties." Viruses 13, no. 7: 1221.
The immunodeficiency observed in HIV-1-infected patients is mainly due to uninfected bystander CD4+ T lymphocyte cell death. The viral envelope glycoproteins (Env), expressed at the surface of infected cells, play a key role in this process. Env triggers macroautophagy/autophagy, a process necessary for subsequent apoptosis, and the production of reactive oxygen species (ROS) in bystander CD4+ T cells. Here, we demonstrate that Env-induced oxidative stress is responsible for their death by apoptosis. Moreover, we report that peroxisomes, organelles involved in the control of oxidative stress, are targeted by Env-mediated autophagy. Indeed, we observe a selective autophagy-dependent decrease in the expression of peroxisomal proteins, CAT and PEX14, upon Env exposure; the downregulation of either BECN1 or SQSTM1/p62 restores their expression levels. Fluorescence studies allowed us to conclude that Env-mediated autophagy degrades these entire organelles and specifically the mature ones. Together, our results on Env-induced pexophagy provide new clues on HIV-1-induced immunodeficiency. Abbreviations: Ab: antibodies; AF: auranofin; AP: anti-proteases; ART: antiretroviral therapy; BafA1: bafilomycin A1; BECN1: beclin 1; CAT: catalase; CD4: CD4 molecule; CXCR4: C-X-C motif chemokine receptor 4; DHR123: dihydrorhodamine 123; Env: HIV-1 envelope glycoproteins; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GFP: green fluorescent protein; GFP-SKL: GFP-serine-lysine-leucine; HEK: human embryonic kidney; HIV-1: type 1 human immunodeficiency virus; HTRF: homogeneous time resolved fluorescence; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; NAC: N-acetyl-cysteine; PARP: poly(ADP-ribose) polymerase; PEX: peroxin; ROS: reactive oxygen species; siRNA: small interfering ribonucleic acid; SQSTM1/p62: sequestosome 1.
Coralie F Daussy; Mathilde Galais; Baptiste Pradel; Véronique Robert-Hebmann; Sophie Sagnier; Sophie Pattingre; Martine Biard-Piechaczyk; Lucile Espert. HIV-1 Env induces pexophagy and an oxidative stress leading to uninfected CD4+ T cell death. Autophagy 2020, 1 -10.
AMA StyleCoralie F Daussy, Mathilde Galais, Baptiste Pradel, Véronique Robert-Hebmann, Sophie Sagnier, Sophie Pattingre, Martine Biard-Piechaczyk, Lucile Espert. HIV-1 Env induces pexophagy and an oxidative stress leading to uninfected CD4+ T cell death. Autophagy. 2020; ():1-10.
Chicago/Turabian StyleCoralie F Daussy; Mathilde Galais; Baptiste Pradel; Véronique Robert-Hebmann; Sophie Sagnier; Sophie Pattingre; Martine Biard-Piechaczyk; Lucile Espert. 2020. "HIV-1 Env induces pexophagy and an oxidative stress leading to uninfected CD4+ T cell death." Autophagy , no. : 1-10.
Cells are constantly challenged by pathogens (bacteria, virus, and fungi), and protein aggregates or chemicals, which can provoke membrane damage at the plasma membrane or within the endo-lysosomal compartments. Detection of endo-lysosomal rupture depends on a family of sugar-binding lectins, known as galectins, which sense the abnormal exposure of glycans to the cytoplasm upon membrane damage. Galectins in conjunction with other factors orchestrate specific membrane damage responses such as the recruitment of the endosomal sorting complex required for transport (ESCRT) machinery to either repair damaged membranes or the activation of autophagy to remove membrane remnants. If not controlled, membrane damage causes the release of harmful components including protons, reactive oxygen species, or cathepsins that will elicit inflammation. In this review, we provide an overview of current knowledge on membrane damage and cellular responses. In particular, we focus on the endo-lysosomal damage triggered by non-enveloped viruses (such as adenovirus) and discuss viral strategies to control the cellular membrane damage response. Finally, we debate the link between autophagy and inflammation in this context and discuss the possibility that virus induced autophagy upon entry limits inflammation.
Coralie F. Daussy; Harald Wodrich. “Repair Me if You Can”: Membrane Damage, Response, and Control from the Viral Perspective. Cells 2020, 9, 2042 .
AMA StyleCoralie F. Daussy, Harald Wodrich. “Repair Me if You Can”: Membrane Damage, Response, and Control from the Viral Perspective. Cells. 2020; 9 (9):2042.
Chicago/Turabian StyleCoralie F. Daussy; Harald Wodrich. 2020. "“Repair Me if You Can”: Membrane Damage, Response, and Control from the Viral Perspective." Cells 9, no. 9: 2042.
ISG15 is an interferon (IFN)-α/β-induced ubiquitin-like protein. It exists as a free molecule, intracellularly and extracellularly, and conjugated to target proteins. Studies in mice have demonstrated a role for Isg15 in antiviral immunity. By contrast, human ISG15 was shown to have critical immune functions, but not in antiviral immunity. Namely, free extracellular ISG15 is crucial in IFN-γ-dependent antimycobacterial immunity, while free intracellular ISG15 is crucial for USP18-mediated downregulation of IFN-α/β signalling. Here we describe ISG15-deficient patients who display no enhanced susceptibility to viruses in vivo, in stark contrast to Isg15-deficient mice. Furthermore, fibroblasts derived from ISG15-deficient patients display enhanced antiviral protection, and expression of ISG15 attenuates viral resistance to WT control levels. The species-specific gain-of-function in antiviral immunity observed in ISG15 deficiency is explained by the requirement of ISG15 to sustain USP18 levels in humans, a mechanism not operating in mice. hTert-immortalized fibroblasts from ISG15-deficient patients (n=3) or controls (n=5) were treated with the indicated concentration of IFN-α2b for 12 h, washed, and allowed to rest for 36 h before infection. (a) Relative IFIT1 (left panel) or MX1 (right panel) mRNA levels at 12 (time of IFN-α2b removal), 24, 48, 72, 96, 120 and 144 h post-priming with 1,000 IU ml−1. (b) Cells were infected with HSV-1-US11-GFP at a multiplicity of infection (MOI) of 1.0 for 24 h, fixed, subjected to Hoechst 33342 nuclear staining, and imaged. Shown are the percentages of cells positive for both GFP and nuclear staining. (c) Cells were infected with HCMV-IE2-YFP at an MOI of 2.0 for 24 h, fixed, and imaged. Shown are the numbers of GFP-positive cells field−1. (d) Cells were infected with IAV PR8-gLuc-PTV1 at an MOI of 10.0 for 24 h. Lysates were collected and assayed for luciferase activity. Shown are the results in relative luminescence units. (e) Cells were infected with SeV-GFP-gLuc at an MOI of 0.1 for 24 h. Supernatants were collected and assayed for luciferase activity. Shown are the results in relative luminescence units. (f) Cells were infected with RVFV at an MOI of 0.01 for 48 h. Supernatants were collected and titered by plaque assay. (g) Cells were infected with NiV-gLuc-P2A-eGFP at an MOI of 0.01 for 24 h. Supernatants were titered by plaque assay. a shows the combined results of two experiments. b,c, and e show a single representative experiments of three performed. d shows the combined results of three experiments. f and g are single experiments performed in the BSL-4. Error bars, s.d. Comparisons made with unpaired t-test. *P<0.05, **P<0.01, ****P<0.0001. NS, not significant. Full size image View in article (a–c) hTert-immortalized fibroblasts from ISG15-deficient patients (n=3) or controls (n=2 or 3) were treated with the indicated concentration of IFN-α2b for 12 h, washed, and allowed to rest for 36 h before infection. (a) Cells were infected with VSV at an MOI of 1.0 for 24 h. Supernatants were titered by TCID50. (b) Cells were infected with VSV–GFP at an MOI of 1.0 for 24 h, fixed, subjected to nuclear staining, and imaged. Representative images are shown for each treatment group. (c) Quantification of panel b. Shown is the percentage of cells positive for both GFP and nuclear staining. (d) and (e) hTert-immortalized fibroblasts from ISG15-deficient patients (n=3) or controls (n=2), untransduced or stably transduced with luciferase, ISG15 or ISG15ΔGG, were mock-treated or primed with 1,000 IU ml−1 IFN-α2b for 12 h, washed, and allowed to rest for 36 h. (d) Relative IFIT1 mRNA levels 48 h post-priming. (e) Fibroblasts were infected with VSV at an MOI of 1.0, 48 h post-priming. Supernatants were collected at 24 h post-infection and titered by TCID50 in duplicate. a,d and e show the combined results of three experiments. b and c show single representative experiments of three performed. Error bars, s.d. Comparisons made with unpaired t-test. *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001. NS, not significant. Full size image View in article (a–d) Age-matched Isg15-deficient (n=2–4 per group) or WT C57BL6/J (n=2-4 group-1) mice received intraperitoneal injections of (a) PBS (mock) or (b–d) 10,000 IU type-I IFN. Animals were sacrificed at the (b) 8 h, (c) 24 h or (d) 96 h post treatment and relative Ifit1 mRNA levels were determined by qPCR. (e) MEFs derived from Isg15-deficient or C57BL/6 J mice were mock-treated or primed with 1000 IU ml−1 type-I IFN for 12 h, washed and allowed to rest for 36 h. Relative mRNA levels for Ifit1 were determined by qPCR at the indicated times post-priming. e shows the combined results of three experiments. Error bars, s.d. Comparisons made with unpaired t-test. NS, not significant. Full size image View in article (a) Primary MEFs from WT and Isg15-deficient mice were primed with murine IFN-β (500 pM) for 6–38 h. Cell lysates (30 μg) were analysed by western blotting with the antibodies indicated. (b) BMM from WT, Isg15-deficient and Ube1L-deficient mice were primed with murine IFN-α4 (250 pM) for 4–36 h. Cell lysates (20 μg) were analysed by western blotting with the antibodies indicated. (c) Murine LL171 cells were transfected with non-silencing control or ISG15 siRNA. 24 h post-transfection, the cells were primed for 1–32 h with murine IFN-β (10 pM). Cell lysates (30 μg) were analysed by western blotting with the antibodies indicated. Full size image View in article (a) HEK293T cells were transfected with a human USP18 expression vector (0.5 μg) alone or with increasing amounts of the human Flag-ISG15ΔGG construct. 48 h post transfection, cell lysates were analysed by western blot with antibodies against USP18 and Flag. (b) Cells were transfected with human USP18...
Scott D. Speer; Zhi Li; Sofija Buta; Béatrice Payelle-Brogard; Li Qian; Frederic Vigant; Erminia Rubino; Thomas Gardner; Tim Wedeking; Mark Hermann; James Duehr; Ozden Sanal; Ilhan Tezcan; Nahal Mansouri; Payam Tabarsi; Davood Mansouri; Véronique Francois-Newton; Coralie F. Daussy; Marisela R. Rodriguez; Deborah J. Lenschow; Alexander N. Freiberg; Domenico Tortorella; Jacob Piehler; Benhur Lee; Adolfo Garcia-Sastre; Sandra Pellegrini; Dusan Bogunovic. ISG15 deficiency and increased viral resistance in humans but not mice. Nature Communications 2016, 7, 11496 .
AMA StyleScott D. Speer, Zhi Li, Sofija Buta, Béatrice Payelle-Brogard, Li Qian, Frederic Vigant, Erminia Rubino, Thomas Gardner, Tim Wedeking, Mark Hermann, James Duehr, Ozden Sanal, Ilhan Tezcan, Nahal Mansouri, Payam Tabarsi, Davood Mansouri, Véronique Francois-Newton, Coralie F. Daussy, Marisela R. Rodriguez, Deborah J. Lenschow, Alexander N. Freiberg, Domenico Tortorella, Jacob Piehler, Benhur Lee, Adolfo Garcia-Sastre, Sandra Pellegrini, Dusan Bogunovic. ISG15 deficiency and increased viral resistance in humans but not mice. Nature Communications. 2016; 7 (1):11496.
Chicago/Turabian StyleScott D. Speer; Zhi Li; Sofija Buta; Béatrice Payelle-Brogard; Li Qian; Frederic Vigant; Erminia Rubino; Thomas Gardner; Tim Wedeking; Mark Hermann; James Duehr; Ozden Sanal; Ilhan Tezcan; Nahal Mansouri; Payam Tabarsi; Davood Mansouri; Véronique Francois-Newton; Coralie F. Daussy; Marisela R. Rodriguez; Deborah J. Lenschow; Alexander N. Freiberg; Domenico Tortorella; Jacob Piehler; Benhur Lee; Adolfo Garcia-Sastre; Sandra Pellegrini; Dusan Bogunovic. 2016. "ISG15 deficiency and increased viral resistance in humans but not mice." Nature Communications 7, no. 1: 11496.