8 results on '"Vinicius G. Suzart"'
Search Results
2. Mycobacterium tuberculosis impairs human memory CD4+ T cell recognition of M2 but not M1-like macrophages
- Author
-
Daniel P. Gail, Vinicius G. Suzart, Weinan Du, Avinaash Kaur Sandhu, Jessica Jarvela, Mary Nantongo, Ivan Mwebaza, Soumya Panigrahi, Michael L. Freeman, David H. Canaday, W. Henry Boom, Richard F. Silver, and Stephen M. Carpenter
- Subjects
Immunology ,Immune response ,Microbiology ,Science - Abstract
Summary: Direct recognition of Mycobacterium tuberculosis (Mtb)-infected cells is required for protection by CD4+ T cells. While impaired T cell recognition of Mtb-infected macrophages was demonstrated in mice, data are lacking for humans. Using T cells and monocyte-derived macrophages (MDMs) from individuals with latent Mtb infection (LTBI), we quantified the frequency of memory CD4+ T cell activation in response to autologous MDMs infected with virulent Mtb. We observed robust T cell activation in response to Mtb infection of M1-like macrophages differentiated using GM-CSF, while M2-like macrophages differentiated using M-CSF were poorly recognized. However, non-infected GM-CSF and M-CSF MDMs loaded with exogenous antigens elicited similar CD4+ T cell activation. IL-10 was preferentially secreted by infected M-CSF MDMs, and neutralization improved T cell activation. These results suggest that preferential infection of macrophages with an M2-like phenotype limits T cell-mediated protection against Mtb. Vaccine development should focus on T cell recognition of Mtb-infected macrophages.
- Published
- 2023
- Full Text
- View/download PDF
3. Multiple site place-of-care manufactured anti-CD19 CAR-T cells induce high remission rates in B-cell malignancy patients
- Author
-
Michael Maschan, Paolo F. Caimi, Jane Reese-Koc, Gabriela Pacheco Sanchez, Ashish A. Sharma, Olga Molostova, Larisa Shelikhova, Dmitriy Pershin, Alexey Stepanov, Yakov Muzalevskii, Vinicius G. Suzart, Folashade Otegbeye, David Wald, Ying Xiong, Darong Wu, Adam Knight, Ibe Oparaocha, Beatrix Ferencz, Andre Roy, Andrew Worden, Winfried Kruger, Michael Kadan, Dina Schneider, Rimas Orentas, Rafick-Pierre Sekaly, Marcos de Lima, and Boro Dropulić
- Subjects
Science - Abstract
Strategies to address the challenges associated with product manufacturing can improve chimeric antigen receptor (CAR) cell–based therapeutics. Here the authors report the results of two clinical trials in patients with B-cell malignancies, showing that place-of-care manufacturing has a low production failure rate with CD19-directed CAR-T cell products inducing high remission rates.
- Published
- 2021
- Full Text
- View/download PDF
4. Trimeric receptor-binding domain of SARS-CoV-2 acts as a potent inhibitor of ACE2 receptor-mediated viral entry
- Author
-
Shrikanth C. Basavarajappa, Angela Rose Liu, Anna Bruchez, Zhenlu Li, Vinicius G. Suzart, Zhonghua Liu, Yinghua Chen, Tsan Sam Xiao, Matthias Buck, and Parameswaran Ramakrishnan
- Subjects
Molecular structure ,Virology ,Science - Abstract
Summary: The COVID-19 pandemic has caused over four million deaths and effective methods to control CoV-2 infection, in addition to vaccines, are needed. The CoV-2 binds to the ACE2 on human cells through the receptor-binding domain (RBD) of the trimeric spike protein. Our modeling studies show that a modified trimeric RBD (tRBD) can interact with three ACE2 receptors, unlike the native spike protein, which binds to only one ACE2. We found that tRBD binds to the ACE2 with 58-fold higher affinity than monomeric RBD (mRBD) and blocks spike-dependent pseudoviral infection over 4-fold more effectively compared to the mRBD. Although mRBD failed to block CoV-2 USA-WA1/2020 infection, tRBD efficiently blocked the true virus infection in plaque assays. We show that tRBD is a potent inhibitor of CoV-2 through both competitive binding to the ACE2 and steric hindrance, and has the potential to emerge as a first-line therapeutic method to control COVID-19.
- Published
- 2022
- Full Text
- View/download PDF
5. Critical role of CD4+ T cells and IFNγ signaling in antibody-mediated resistance to Zika virus infection
- Author
-
Carolina G. O. Lucas, Jamil Z. Kitoko, Fabricio M. Ferreira, Vinicius G. Suzart, Michelle P. Papa, Sharton V. A. Coelho, Cecilia B. Cavazzoni, Heitor A. Paula-Neto, Priscilla C. Olsen, Akiko Iwasaki, Renata M. Pereira, Pedro M. Pimentel-Coelho, Andre M. Vale, Luciana B. de Arruda, and Marcelo T. Bozza
- Subjects
Science - Abstract
Characterization of protective immunity to Zika virus has largely focussed on CD8+ T cells and antibody-mediated protection. Here the authors show roles for CD4+ T cells and the associated IFNγ signaling in antibody-mediated resistance to Zika virus infection.
- Published
- 2018
- Full Text
- View/download PDF
6. Trimeric receptor-binding domain of SARS-CoV-2 acts as a potent inhibitor of ACE2 receptor-mediated viral entry
- Author
-
Shrikanth C. Basavarajappa, Angela Rose Liu, Anna Bruchez, Zhenlu Li, Vinicius G. Suzart, Zhonghua Liu, Yinghua Chen, Tsan Sam Xiao, Matthias Buck, and Parameswaran Ramakrishnan
- Subjects
Multidisciplinary - Abstract
The COVID-19 pandemic has caused over four million deaths and effective methods to control CoV-2 infection, in addition to vaccines, are needed. The CoV-2 binds to the ACE2 on human cells through the receptor-binding domain (RBD) of the trimeric spike protein. Our modeling studies show that a modified trimeric RBD (tRBD) can interact with three ACE2 receptors, unlike the native spike protein, which binds to only one ACE2. We found that tRBD binds to the ACE2 with 58-fold higher affinity than monomeric RBD (mRBD) and blocks spike-dependent pseudoviral infection over 4-fold more effectively compared to the mRBD. Although mRBD failed to block CoV-2 USA-WA1/2020 infection, tRBD efficiently blocked the true virus infection in plaque assays. We show that tRBD is a potent inhibitor of CoV-2 through both competitive binding to the ACE2 and steric hindrance, and has the potential to emerge as a first-line therapeutic method to control COVID-19.
- Published
- 2021
7. Mutants of human ACE2 differentially promote SARS-CoV and SARS-CoV-2 spike mediated infection
- Author
-
Kenneth A. Matreyek, Vinicius G. Suzart, Anna M. Bruchez, Sarah Roelle, and Nidhi Shukla
- Subjects
RNA viruses ,Proteomics ,Coronaviruses ,Molecular biology ,viruses ,Mutant ,medicine.disease_cause ,Severe Acute Respiratory Syndrome ,Biochemistry ,0302 clinical medicine ,Spectrum Analysis Techniques ,Biology (General) ,skin and connective tissue diseases ,Pathology and laboratory medicine ,Coronavirus ,Staining ,0303 health sciences ,Mutation ,Cell Staining ,Medical microbiology ,Flow Cytometry ,Cell biology ,Severe acute respiratory syndrome-related coronavirus ,Spectrophotometry ,Spike Glycoprotein, Coronavirus ,Viruses ,293T cells ,Cell lines ,Angiotensin-Converting Enzyme 2 ,Cytophotometry ,SARS CoV 2 ,Pathogens ,Biological cultures ,hormones, hormone substitutes, and hormone antagonists ,Research Article ,SARS coronavirus ,QH301-705.5 ,Transgene ,Immunology ,Mutation, Missense ,Biology ,DNA construction ,Transfection ,Microbiology ,Virus ,03 medical and health sciences ,Virology ,Genetics ,medicine ,Humans ,Avidity ,030304 developmental biology ,Medicine and health sciences ,Biology and life sciences ,SARS-CoV-2 ,HEK 293 cells ,fungi ,Organisms ,Viral pathogens ,COVID-19 ,RC581-607 ,Microbial pathogens ,body regions ,Research and analysis methods ,HEK293 Cells ,Molecular biology techniques ,Cell culture ,Specimen Preparation and Treatment ,Plasmid Construction ,Parasitology ,Immunologic diseases. Allergy ,030217 neurology & neurosurgery ,Protein Abundance - Abstract
SARS-CoV and SARS-CoV-2 encode spike proteins that bind human ACE2 on the cell surface to enter target cells during infection. A small fraction of humans encode variants of ACE2, thus altering the biochemical properties at the protein interaction interface. These and other ACE2 coding mutants can reveal how the spike proteins of each virus may differentially engage the ACE2 protein surface during infection. We created an engineered HEK 293T cell line for facile stable transgenic modification, and expressed the major human ACE2 allele or 28 of its missense mutants, 24 of which are possible through single nucleotide changes from the human reference sequence. Infection with SARS-CoV or SARS-CoV-2 spike pseudotyped lentiviruses revealed that high ACE2 cell-surface expression could mask the effects of impaired binding during infection. Drastically reducing ACE2 cell surface expression revealed a range of infection efficiencies across the panel of mutants. Our infection results revealed a non-linear relationship between soluble SARS-CoV-2 RBD binding to ACE2 and pseudovirus infection, supporting a major role for binding avidity during entry. While ACE2 mutants D355N, R357A, and R357T abrogated entry by both SARS-CoV and SARS-CoV-2 spike proteins, the Y41A mutant inhibited SARS-CoV entry much more than SARS-CoV-2, suggesting differential utilization of the ACE2 side-chains within the largely overlapping interaction surfaces utilized by the two CoV spike proteins. These effects correlated well with cytopathic effects observed during SARS-CoV-2 replication in ACE2-mutant cells. The panel of ACE2 mutants also revealed altered ACE2 surface dependencies by the N501Y spike variant, including a near-complete utilization of the K353D ACE2 variant, despite decreased infection mediated by the parental SARS-CoV-2 spike. Our results clarify the relationship between ACE2 abundance, binding, and infection, for various SARS-like coronavirus spike proteins and their mutants, and inform our understanding for how changes to ACE2 sequence may correspond with different susceptibilities to infection., Author summary SARS-like coronaviruses, such as SARS-CoV-2, use their spike proteins to bind a common surface on the human ACE2 protein to gain entry and subsequently infect cells. We used site-specific genomic integration and expression of WT ACE2 or its missense variants, many of them previously observed in human exomes, to determine how ACE2 sequence and abundance correspond to infectability by SARS-CoV or SARS-CoV-2. We found that reduced binding only partially corresponded to infection, and mainly only at lower ACE2 abundance levels. We observed some human ACE2 variants differentially affect SARS-CoV, SARS-CoV-2, or SARs-CoV-2 N501Y spike variant pseudovirus entry, showing that each viral spike binds ACE2 in a unique manner. Our results provide improved quantitative understanding for how ACE2 sequence and abundance correlate with infectivity, with implications for how natural human ACE2 variants, or variants observed in related species, may impact susceptibility to infection. These genetic tools can be repurposed to characterize future SARS-CoV-2 spike variants, or to better understand how receptor protein sequences correspond with entry by zoonotic viruses during cross-species transmission events.
- Published
- 2021
8. Mutants of human ACE2 differentially promote SARS-CoV and SARS-CoV-2 spike mediated infection.
- Author
-
Nidhi Shukla, Sarah M Roelle, Vinicius G Suzart, Anna M Bruchez, and Kenneth A Matreyek
- Subjects
Immunologic diseases. Allergy ,RC581-607 ,Biology (General) ,QH301-705.5 - Abstract
SARS-CoV and SARS-CoV-2 encode spike proteins that bind human ACE2 on the cell surface to enter target cells during infection. A small fraction of humans encode variants of ACE2, thus altering the biochemical properties at the protein interaction interface. These and other ACE2 coding mutants can reveal how the spike proteins of each virus may differentially engage the ACE2 protein surface during infection. We created an engineered HEK 293T cell line for facile stable transgenic modification, and expressed the major human ACE2 allele or 28 of its missense mutants, 24 of which are possible through single nucleotide changes from the human reference sequence. Infection with SARS-CoV or SARS-CoV-2 spike pseudotyped lentiviruses revealed that high ACE2 cell-surface expression could mask the effects of impaired binding during infection. Drastically reducing ACE2 cell surface expression revealed a range of infection efficiencies across the panel of mutants. Our infection results revealed a non-linear relationship between soluble SARS-CoV-2 RBD binding to ACE2 and pseudovirus infection, supporting a major role for binding avidity during entry. While ACE2 mutants D355N, R357A, and R357T abrogated entry by both SARS-CoV and SARS-CoV-2 spike proteins, the Y41A mutant inhibited SARS-CoV entry much more than SARS-CoV-2, suggesting differential utilization of the ACE2 side-chains within the largely overlapping interaction surfaces utilized by the two CoV spike proteins. These effects correlated well with cytopathic effects observed during SARS-CoV-2 replication in ACE2-mutant cells. The panel of ACE2 mutants also revealed altered ACE2 surface dependencies by the N501Y spike variant, including a near-complete utilization of the K353D ACE2 variant, despite decreased infection mediated by the parental SARS-CoV-2 spike. Our results clarify the relationship between ACE2 abundance, binding, and infection, for various SARS-like coronavirus spike proteins and their mutants, and inform our understanding for how changes to ACE2 sequence may correspond with different susceptibilities to infection.
- Published
- 2021
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.