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Article ; Online: Comprehensive analysis of COVID-19 during pregnancy.

Moore, Kathryn M / Suthar, Mehul S

Biochemical and biophysical research communications

2020 Volume 538, Page(s) 180–186

Abstract: The COVID-19 pandemic resulting from the emergence of the coronavirus SARS-CoV-2 remains a major global health concern. Pregnant individuals are more likely to develop severe COVID-19 and a number of pregnancy complications have been observed in COVID-19 ...

Abstract	The COVID-19 pandemic resulting from the emergence of the coronavirus SARS-CoV-2 remains a major global health concern. Pregnant individuals are more likely to develop severe COVID-19 and a number of pregnancy complications have been observed in COVID-19 patients. To date, little is known about the impact of COVID-19 on pregnancy. In this review, we examine key aspects of pregnancy that may be impacted by COVID-19 and summarize the current literature on SARS-CoV-2 infection of the placenta and in utero vertical transmission. Furthermore, we highlight recent studies exploring the role of the maternal antibody response to SARS-CoV-2 during pregnancy and the passive transfer of maternal antibodies from mothers with COVID-19 to fetus.
MeSH term(s)	Antibodies, Viral/immunology ; COVID-19/blood ; COVID-19/immunology ; Female ; Humans ; Infectious Disease Transmission, Vertical ; Maternal-Fetal Exchange/immunology ; Placenta/virology ; Pregnancy ; Pregnancy Complications, Infectious/virology ; SARS-CoV-2/immunology ; Uterus/virology
Chemical Substances	Antibodies, Viral
Language	English
Publishing date	2020-12-24
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	205723-2
ISSN	1090-2104 ; 0006-291X ; 0006-291X
ISSN (online)	1090-2104 ; 0006-291X
ISSN	0006-291X
DOI	10.1016/j.bbrc.2020.12.064
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Zs.A 116: Show issues

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Article ; Online: Innate antiviral immunity: how prior exposures can guide future responses.

Tomalka, Jeffrey A / Suthar, Mehul S / Diamond, Michael S / Sekaly, Rafick P

Trends in immunology

2022 Volume 43, Issue 9, Page(s) 696–705

Abstract: Innate immunity is an intrinsic baseline defense in cells, with its earliest origins in bacteria, and with key roles in defense against pathogens and in the activation of B and T cell responses. In mammals, the efficacy of innate immunity in initiating ... ...

Abstract	Innate immunity is an intrinsic baseline defense in cells, with its earliest origins in bacteria, and with key roles in defense against pathogens and in the activation of B and T cell responses. In mammals, the efficacy of innate immunity in initiating the cascades that lead to pathogen control results from the interplay of transcriptomic, epigenomic, and proteomic responses regulating immune activation and long-lived pathogen-specific memory responses. Recent studies suggest that intrinsic innate immunity is modulated by individual exposure histories - prior infections, vaccinations, and metabolites of microbial origin - and this promotes, or impairs, the development of efficacious innate immune responses. Understanding how environmental factors regulate innate immunity and boost protection from infection or response to vaccination could be a valuable tool for pandemic preparedness.
MeSH term(s)	Animals ; Antiviral Agents ; Humans ; Immunity, Innate ; Mammals ; Pandemics ; Proteomics ; T-Lymphocytes
Chemical Substances	Antiviral Agents
Language	English
Publishing date	2022-07-28
Publishing country	England
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural
ZDB-ID	2036831-8
ISSN	1471-4981 ; 1471-4906
ISSN (online)	1471-4981
ISSN	1471-4906
DOI	10.1016/j.it.2022.07.001
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Zs.A 1601: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 2: Show issues

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Article ; Online: Fighting the SARS-CoV-2 pandemic requires a global approach to understanding the heterogeneity of vaccine responses.

Tomalka, Jeffrey A / Suthar, Mehul S / Deeks, Steven G / Sekaly, Rafick Pierre

Nature immunology

2022 Volume 23, Issue 3, Page(s) 360–370

Abstract: Host genetic and environmental factors including age, biological sex, diet, geographical location, microbiome composition and metabolites converge to influence innate and adaptive immune responses to vaccines. Failure to understand and account for these ... ...

Abstract	Host genetic and environmental factors including age, biological sex, diet, geographical location, microbiome composition and metabolites converge to influence innate and adaptive immune responses to vaccines. Failure to understand and account for these factors when investigating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine efficacy may impair the development of the next generation of vaccines. Most studies aimed at identifying mechanisms of vaccine-mediated immune protection have focused on adaptive immune responses. It is well established, however, that mobilization of the innate immune response is essential to the development of effective cellular and humoral immunity. A comprehensive understanding of the innate immune response and environmental factors that contribute to the development of broad and durable cellular and humoral immune responses to SARS-CoV-2 and other vaccines requires a holistic and unbiased approach. Along with optimization of the immunogen and vectors, the development of adjuvants based on our evolving understanding of how the innate immune system shapes vaccine responses will be essential. Defining the innate immune mechanisms underlying the establishment of long-lived plasma cells and memory T cells could lead to a universal vaccine for coronaviruses, a key biomedical priority.
MeSH term(s)	Antibodies, Viral ; Biological Variation, Population ; COVID-19/epidemiology ; COVID-19/prevention & control ; COVID-19/virology ; COVID-19 Vaccines/administration & dosage ; COVID-19 Vaccines/immunology ; Global Health ; Host Microbial Interactions/immunology ; Host-Pathogen Interactions/immunology ; Humans ; Immunity ; Immunity, Humoral ; Immunity, Innate ; Immunogenicity, Vaccine ; Immunologic Memory ; Microbiota/immunology ; Pandemics ; Public Health Surveillance ; SARS-CoV-2/immunology ; Vaccination
Chemical Substances	Antibodies, Viral ; COVID-19 Vaccines
Language	English
Publishing date	2022-02-24
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2016987-5
ISSN	1529-2916 ; 1529-2908
ISSN (online)	1529-2916
ISSN	1529-2908
DOI	10.1038/s41590-022-01130-4
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Zs.A 5294: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 42: Show issues

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Article ; Online: Editorial overview: Viral immunology: Generating immunity to diverse viral pathogens.

Hickman, Heather D / Suthar, Mehul S

Current opinion in virology

2018 Volume 28, Page(s) viii–x

MeSH term(s)	Adaptive Immunity ; Animals ; Humans ; Immunity, Innate ; T-Lymphocytes/immunology ; Virus Diseases/immunology
Keywords	covid19
Language	English
Publishing date	2018-03-01
Publishing country	Netherlands
Document type	Editorial ; Introductory Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2611378-8
ISSN	1879-6265 ; 1879-6257
ISSN (online)	1879-6265
ISSN	1879-6257
DOI	10.1016/j.coviro.2018.02.003
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Covaxin (BBV152) Vaccine Neutralizes SARS-CoV-2 Delta and Omicron variants

Edara, Venkata V / Patel, Mit / Suthar, Mehul S

medRxiv

Abstract: The SARS-CoV-2 vaccine BBV152/Covaxin is well-tolerated and was shown to be 77.8% efficacious against symptomatic and 93.4% efficacious against severe symptomatic COVID-19 disease in adults. Previous studies have shown that sera from Covaxin vaccinated ... ...

Abstract	The SARS-CoV-2 vaccine BBV152/Covaxin is well-tolerated and was shown to be 77.8% efficacious against symptomatic and 93.4% efficacious against severe symptomatic COVID-19 disease in adults. Previous studies have shown that sera from Covaxin vaccinated individuals have neutralizing activity against B.1.1.7 (Alpha), B.1.351 (Beta), B.1.617.2 (Delta), B.1.1.28 (Zeta), and B.1.617.1 (Kappa) SARS-CoV-2 variants. The B.1.1.529 variant (Omicron) recently emerged in November 2021 and has spread throughout the world. The Omicron variant has more than 30 mutations within the spike protein that could impact vaccine-mediated immunity. We used a live virus neutralization assay to evaluate the neutralizing activity against the Omicron variant of sera collected from subjects who received a booster dose (6- month after primary series last dose) of Covaxin. We found that sera from Covaxin boosted individuals showed neutralizing activity against D614G (vaccine strain), Delta, and Omicron variants. One hundred percent of boosted subjects showed neutralizing activity against the Delta variant while over 90% of boosted subjects showed neutralizing activity against the Omicron variant. These findings show that a booster dose of Covaxin can generate robust neutralizing antibody responses against the Omicron variant.
Keywords	covid19
Language	English
Publishing date	2022-01-28
Publisher	Cold Spring Harbor Laboratory Press
Document type	Article ; Online
DOI	10.1101/2022.01.24.22269189
Database	COVID19

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Article ; Online: Cross-Reactive Antibodies during Zika Virus Infection: Protection, Pathogenesis, and Placental Seeding.

Zimmerman, Matthew G / Wrammert, Jens / Suthar, Mehul S

Cell host & microbe

2020 Volume 27, Issue 1, Page(s) 14–24

Abstract: Humoral immunity is an essential component of the protective immune response to flavivirus infection. Typically, primary infection generates a robust neutralizing antibody response that mediates viral control and protection. It is becoming increasingly ... ...

Abstract	Humoral immunity is an essential component of the protective immune response to flavivirus infection. Typically, primary infection generates a robust neutralizing antibody response that mediates viral control and protection. It is becoming increasingly apparent that secondary infection with a closely related flavivirus strain can result in immunological cross-reactivity; however, the consequences to infection outcome remain controversial. Since its introduction to Brazil in 2015, Zika virus (ZIKV) has caused an epidemic of fetal congenital malformations within the Americas. Because ZIKV is a mosquito-borne flavivirus with a high degree of sequence and structural homology to Dengue virus (DENV), the role of immunological cross-reactivity in ZIKV and DENV infections has become a great concern. In this review, we highlight contemporary findings that implicate a role for flavivirus antibodies in mediating protection, contributing to pathogenesis, and seeding the human placenta.
MeSH term(s)	Animals ; Antibodies, Neutralizing/immunology ; Antibodies, Viral ; Cross Reactions/immunology ; Culicidae/virology ; Dengue/immunology ; Dengue Virus/immunology ; Female ; Flavivirus/immunology ; Humans ; Immunity, Humoral ; Infectious Disease Transmission, Vertical ; Placenta/immunology ; Placenta/virology ; Pregnancy ; Viral Vaccines ; Zika Virus/immunology ; Zika Virus Infection/immunology ; Zika Virus Infection/pathology ; Zika Virus Infection/therapy
Chemical Substances	Antibodies, Neutralizing ; Antibodies, Viral ; Viral Vaccines
Language	English
Publishing date	2020-01-11
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2278004-X
ISSN	1934-6069 ; 1931-3128
ISSN (online)	1934-6069
ISSN	1931-3128
DOI	10.1016/j.chom.2019.12.003
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Zs.A 6578: Show issues

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Article: Single cell analysis reveals an antiviral network that controls Zika virus infection in human dendritic cells.

Moore, Kathryn M / Pelletier, Adam-Nicolas / Lapp, Stacey / Metz, Amanda / Tharp, Gregory K / Lee, Michelle / Bhasin, Swati Sharma / Bhasin, Manoj / Sékaly, Rafick-Pierre / Bosinger, Steven E / Suthar, Mehul S

bioRxiv : the preprint server for biology

2024

Abstract: Zika virus (ZIKV) is a mosquito-borne flavivirus that caused an epidemic in the Americas in 2016 and is linked to severe neonatal birth defects, including microcephaly and spontaneous abortion. To better understand the host response to ZIKV infection, we ...

Abstract	Zika virus (ZIKV) is a mosquito-borne flavivirus that caused an epidemic in the Americas in 2016 and is linked to severe neonatal birth defects, including microcephaly and spontaneous abortion. To better understand the host response to ZIKV infection, we adapted the 10x Genomics Chromium single cell RNA sequencing (scRNA-seq) assay to simultaneously capture viral RNA and host mRNA. Using this assay, we profiled the antiviral landscape in a population of human moDCs infected with ZIKV at the single cell level. The bystander cells, which lacked detectable viral RNA, expressed an antiviral state that was enriched for genes coinciding predominantly with a type I interferon (IFN) response. Within the infected cells, viral RNA negatively correlated with type I IFN dependent and independent genes (antiviral module). We modeled the ZIKV specific antiviral state at the protein level leveraging experimentally derived protein-interaction data. We identified a highly interconnected network between the antiviral module and other host proteins. In this work, we propose a new paradigm for evaluating the antiviral response to a specific virus, combining an unbiased list of genes that highly correlate with viral RNA on a per cell basis with experimental protein interaction data. Our ZIKV-inclusive scRNA-seq assay will serve as a useful tool to gaining greater insight into the host response to ZIKV and can be applied more broadly to the flavivirus field.
Language	English
Publishing date	2024-01-21
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.01.19.576293
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Article ; Online: Atovaquone and Pibrentasvir Inhibit the SARS-CoV-2 Endoribonuclease and Restrict Infection In Vitro but Not In Vivo.

von Beck, Troy / Mena Hernandez, Luis / Zhou, Hongyi / Floyd, Katharine / Suthar, Mehul S / Skolnick, Jeffrey / Jacob, Joshy

Viruses

2023 Volume 15, Issue 9

Abstract: The emergence of SARS-CoV-1 in 2003 followed by MERS-CoV and now SARS-CoV-2 has proven the latent threat these viruses pose to humanity. While the SARS-CoV-2 pandemic has shifted to a stage of endemicity, the threat of new coronaviruses emerging from ... ...

Abstract	The emergence of SARS-CoV-1 in 2003 followed by MERS-CoV and now SARS-CoV-2 has proven the latent threat these viruses pose to humanity. While the SARS-CoV-2 pandemic has shifted to a stage of endemicity, the threat of new coronaviruses emerging from animal reservoirs remains. To address this issue, the global community must develop small molecule drugs targeting highly conserved structures in the coronavirus proteome. Here, we characterized existing drugs for their ability to inhibit the endoribonuclease activity of the SARS-CoV-2 non-structural protein 15 (nsp15) via in silico, in vitro, and in vivo techniques. We have identified nsp15 inhibition by the drugs pibrentasvir and atovaquone which effectively inhibit SARS-CoV-2 and HCoV-OC43 at low micromolar concentrations in cell cultures. Furthermore, atovaquone, but not pibrentasvir, is observed to modulate HCoV-OC43 dsRNA and infection in a manner consistent with nsp15 inhibition. Although neither pibrentasvir nor atovaquone translate to clinical efficacy in a murine prophylaxis model of SARS-CoV-2 infection, atovaquone may serve as a basis for the design of future nsp15 inhibitors.
MeSH term(s)	Animals ; Mice ; SARS-CoV-2/metabolism ; COVID-19 ; Atovaquone/pharmacology ; Endoribonucleases/metabolism ; Coronavirus OC43, Human
Chemical Substances	Atovaquone (Y883P1Z2LT) ; pibrentasvir (2WU922TK3L) ; Endoribonucleases (EC 3.1.-)
Language	English
Publishing date	2023-08-30
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v15091841
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Article ; Online: Neutralizing Antibodies Against SARS-CoV-2 Variants After Infection and Vaccination.

Edara, Venkata Viswanadh / Hudson, William H / Xie, Xuping / Ahmed, Rafi / Suthar, Mehul S

JAMA

2021 Volume 325, Issue 18, Page(s) 1896–1898

MeSH term(s)	Antibodies, Neutralizing/blood ; Antibodies, Viral/blood ; COVID-19/immunology ; COVID-19 Serological Testing ; COVID-19 Vaccines/immunology ; Humans ; Immunogenicity, Vaccine ; SARS-CoV-2/immunology
Chemical Substances	Antibodies, Neutralizing ; Antibodies, Viral ; COVID-19 Vaccines
Language	English
Publishing date	2021-02-15
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2958-0
ISSN	1538-3598 ; 0254-9077 ; 0002-9955 ; 0098-7484
ISSN (online)	1538-3598
ISSN	0254-9077 ; 0002-9955 ; 0098-7484
DOI	10.1001/jama.2021.4388
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Ua VI Zs.88: Show issues

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Article ; Online: Single-cell analysis reveals an antiviral network that controls Zika virus infection in human dendritic cells.

Journal of virology

2024 , Page(s) e0019424

Abstract	Zika virus (ZIKV) is a mosquito-borne flavivirus that caused an epidemic in the Americas in 2016 and is linked to severe neonatal birth defects, including microcephaly and spontaneous abortion. To better understand the host response to ZIKV infection, we adapted the 10× Genomics Chromium single-cell RNA sequencing (scRNA-seq) assay to simultaneously capture viral RNA and host mRNA. Using this assay, we profiled the antiviral landscape in a population of human monocyte-derived dendritic cells infected with ZIKV at the single-cell level. The bystander cells, which lacked detectable viral RNA, expressed an antiviral state that was enriched for genes coinciding predominantly with a type I interferon (IFN) response. Within the infected cells, viral RNA negatively correlated with type I IFN-dependent and -independent genes (the antiviral module). We modeled the ZIKV-specific antiviral state at the protein level, leveraging experimentally derived protein interaction data. We identified a highly interconnected network between the antiviral module and other host proteins. In this work, we propose a new paradigm for evaluating the antiviral response to a specific virus, combining an unbiased list of genes that highly correlate with viral RNA on a per-cell basis with experimental protein interaction data. Importance: Zika virus (ZIKV) remains a public health threat given its potential for re-emergence and the detrimental fetal outcomes associated with infection during pregnancy. Understanding the dynamics between ZIKV and its host is critical to understanding ZIKV pathogenesis. Through ZIKV-inclusive single-cell RNA sequencing (scRNA-seq), we demonstrate on the single-cell level the dynamic interplay between ZIKV and the host: the transcriptional program that restricts viral infection and ZIKV-mediated inhibition of that response. Our ZIKV-inclusive scRNA-seq assay will serve as a useful tool for gaining greater insight into the host response to ZIKV and can be applied more broadly to the flavivirus field.
Language	English
Publishing date	2024-04-03
Publishing country	United States
Document type	Journal Article
ZDB-ID	80174-4
ISSN	1098-5514 ; 0022-538X
ISSN (online)	1098-5514
ISSN	0022-538X
DOI	10.1128/jvi.00194-24
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