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Article ; Online: Omicron Spike confers enhanced infectivity and interferon resistance to SARS-CoV-2 in human nasal tissue.

Shi, Guoli / Li, Tiansheng / Lai, Kin Kui / Johnson, Reed F / Yewdell, Jonathan W / Compton, Alex A

2024 Volume 15, Issue 1, Page(s) 889

Abstract: Omicron emerged following COVID-19 vaccination campaigns, displaced previous SARS-CoV-2 variants of concern worldwide, and gave rise to lineages that continue to spread. Here, we show that Omicron exhibits increased infectivity in primary adult upper ... ...

Abstract	Omicron emerged following COVID-19 vaccination campaigns, displaced previous SARS-CoV-2 variants of concern worldwide, and gave rise to lineages that continue to spread. Here, we show that Omicron exhibits increased infectivity in primary adult upper airway tissue relative to Delta. Using recombinant forms of SARS-CoV-2 and nasal epithelial cells cultured at the liquid-air interface, we show that mutations unique to Omicron Spike enable enhanced entry into nasal tissue. Unlike earlier variants of SARS-CoV-2, our findings suggest that Omicron enters nasal cells independently of serine transmembrane proteases and instead relies upon metalloproteinases to catalyze membrane fusion. Furthermore, we demonstrate that this entry pathway unlocked by Omicron Spike enables evasion from constitutive and interferon-induced antiviral factors that restrict SARS-CoV-2 entry following attachment. Therefore, the increased transmissibility exhibited by Omicron in humans may be attributed not only to its evasion of vaccine-elicited adaptive immunity, but also to its superior invasion of nasal epithelia and resistance to the cell-intrinsic barriers present therein.
MeSH term(s)	Adult ; Humans ; Interferons ; SARS-CoV-2/genetics ; COVID-19 Vaccines ; COVID-19 ; Nasal Mucosa ; Serine Endopeptidases/genetics ; Serine Proteases ; Spike Glycoprotein, Coronavirus/genetics
Chemical Substances	Interferons (9008-11-1) ; COVID-19 Vaccines ; Serine Endopeptidases (EC 3.4.21.-) ; Serine Proteases (EC 3.4.-) ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2
Language	English
Publishing date	2024-01-30
Publishing country	England
Document type	Journal Article
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-024-45075-8
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Omicron Spike confers enhanced infectivity and interferon resistance to SARS-CoV-2 in human nasal tissue.

Shi, Guoli / Li, Tiansheng / Lai, Kin Kui / Johnson, Reed F / Yewdell, Jonathan W / Compton, Alex A

bioRxiv : the preprint server for biology

2023

Abstract	Omicron emerged following COVID-19 vaccination campaigns, displaced previous SARS-CoV-2 variants of concern worldwide, and gave rise to lineages that continue to spread. Here, we show that Omicron exhibits increased infectivity in primary adult upper airway tissue relative to Delta. Using recombinant forms of SARS-CoV-2 and nasal epithelial cells cultured at the liquid-air interface, enhanced infectivity maps to the step of cellular entry and evolved recently through mutations unique to Omicron Spike. Unlike earlier variants of SARS-CoV-2, Omicron enters nasal cells independently of serine transmembrane proteases and instead relies upon metalloproteinases to catalyze membrane fusion. This entry pathway unlocked by Omicron Spike enables evasion of constitutive and interferon-induced antiviral factors that restrict SARS-CoV-2 entry following attachment. Therefore, the increased transmissibility exhibited by Omicron in humans may be attributed not only to its evasion of vaccine-elicited adaptive immunity, but also to its superior invasion of nasal epithelia and resistance to the cell-intrinsic barriers present therein.
Language	English
Publishing date	2023-10-12
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.05.06.539698
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Article ; Online: Advances and Challenges in Molecular Imaging of Viral Infections.

Lau, Chuen-Yen / Martinez-Orengo, Neysha / Lyndaker, Anna / Flavahan, Kelly / Johnson, Reed F / Shah, Swati / Hammoud, Dima A

The Journal of infectious diseases

2023 Volume 228, Issue Suppl 4, Page(s) S270–S280

Abstract: Molecular imaging of viral infection, using a variety of advanced imaging techniques such as optical and nuclear imaging, can and has been used for direct visualization of the virus as well as assessment of virus-host interactions. Unlike imaging of ... ...

Abstract	Molecular imaging of viral infection, using a variety of advanced imaging techniques such as optical and nuclear imaging, can and has been used for direct visualization of the virus as well as assessment of virus-host interactions. Unlike imaging of other pathogens such as bacteria and fungi, challenging aspects of imaging viral infections include the small size of viruses, the complexity of viral infection animal models (eg, species dependence), and the high-level containment needs for many high-consequence pathogens, among others. In this review, using representative viral infections, we discuss how molecular imaging can reveal real-time infection dynamics, improve our understanding of disease pathogenesis, and guide optimization of treatment and prevention strategies. Key findings from human and animal studies are highlighted.
MeSH term(s)	Animals ; Humans ; Virus Diseases/diagnostic imaging ; Viruses ; Host Microbial Interactions ; Molecular Imaging
Language	English
Publishing date	2023-10-02
Publishing country	United States
Document type	Review ; Journal Article ; Research Support, N.I.H., Intramural
ZDB-ID	3019-3
ISSN	1537-6613 ; 0022-1899
ISSN (online)	1537-6613
ISSN	0022-1899
DOI	10.1093/infdis/jiad247
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Article ; Online: Letter to the Editor Regarding Optimizing Selection of Biologics in Inflammatory Bowel Disease: Development of an Online Patient Decision Aid Using Conjoint Analysis.

Johnson, Reed F / Reed, Shelby / Gonzalez, Juan Marcos

The American journal of gastroenterology

2018 Volume 113, Issue 11, Page(s) 1720

MeSH term(s)	Biological Products ; Decision Support Techniques ; Humans ; Inflammatory Bowel Diseases
Chemical Substances	Biological Products
Language	English
Publishing date	2018-07-03
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	390122-1
ISSN	1572-0241 ; 0002-9270
ISSN (online)	1572-0241
ISSN	0002-9270
DOI	10.1038/s41395-018-0186-5
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Article ; Online: Live-attenuated pediatric parainfluenza vaccine expressing 6P-stabilized SARS-CoV-2 spike protein is protective against SARS-CoV-2 variants in hamsters.

Liu, Xueqiao / Park, Hong-Su / Matsuoka, Yumiko / Santos, Celia / Yang, Lijuan / Luongo, Cindy / Moore, Ian N / Johnson, Reed F / Garza, Nicole L / Zhang, Peng / Lusso, Paolo / Best, Sonja M / Buchholz, Ursula J / Le Nouën, Cyril

PLoS pathogens

2023 Volume 19, Issue 6, Page(s) e1011057

Abstract: The pediatric live-attenuated bovine/human parainfluenza virus type 3 (B/HPIV3)-vectored vaccine expressing the prefusion-stabilized SARS-CoV-2 spike (S) protein (B/HPIV3/S-2P) was previously evaluated in vitro and in hamsters. To improve its ... ...

Abstract	The pediatric live-attenuated bovine/human parainfluenza virus type 3 (B/HPIV3)-vectored vaccine expressing the prefusion-stabilized SARS-CoV-2 spike (S) protein (B/HPIV3/S-2P) was previously evaluated in vitro and in hamsters. To improve its immunogenicity, we generated B/HPIV3/S-6P, expressing S further stabilized with 6 proline mutations (S-6P). Intranasal immunization of hamsters with B/HPIV3/S-6P reproducibly elicited significantly higher serum anti-S IgA/IgG titers than B/HPIV3/S-2P; hamster sera efficiently neutralized variants of concern (VoCs), including Omicron variants. B/HPIV3/S-2P and B/HPIV3/S-6P immunization protected hamsters against weight loss and lung inflammation following SARS-CoV-2 challenge with the vaccine-matched strain WA1/2020 or VoCs B.1.1.7/Alpha or B.1.351/Beta and induced near-sterilizing immunity. Three weeks post-challenge, B/HPIV3/S-2P- and B/HPIV3/S-6P-immunized hamsters exhibited a robust anamnestic serum antibody response with increased neutralizing potency to VoCs, including Omicron sublineages. B/HPIV3/S-6P primed for stronger anamnestic antibody responses after challenge with WA1/2020 than B/HPIV3/S-2P. B/HPIV3/S-6P will be evaluated as an intranasal vaccine to protect infants against both HPIV3 and SARS-CoV-2.
MeSH term(s)	Cricetinae ; Humans ; Animals ; Cattle ; Child ; SARS-CoV-2 ; Spike Glycoprotein, Coronavirus/genetics ; Antibodies, Viral ; Viral Fusion Proteins ; Vaccines, Attenuated ; COVID-19/prevention & control ; Parainfluenza Virus 3, Human ; Paramyxoviridae Infections ; Antibodies, Neutralizing
Chemical Substances	spike protein, SARS-CoV-2 ; Spike Glycoprotein, Coronavirus ; Antibodies, Viral ; Viral Fusion Proteins ; Vaccines, Attenuated ; Antibodies, Neutralizing
Language	English
Publishing date	2023-06-23
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Intramural
ZDB-ID	2205412-1
ISSN	1553-7374 ; 1553-7374
ISSN (online)	1553-7374
ISSN	1553-7374
DOI	10.1371/journal.ppat.1011057
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Article ; Online: Co-infection of mice with SARS-CoV-2 and

Baker, Paul J / Amaral, Eduardo P / Castro, Ehydel / Bohrer, Andrea C / Torres-Juárez, Flor / Jordan, Cassandra M / Nelson, Christine E / Barber, Daniel L / Johnson, Reed F / Hilligan, Kerry L / Mayer-Barber, Katrin D

Frontiers in immunology

2023 Volume 14, Page(s) 1240419

Abstract: Viral co-infections have been implicated in worsening tuberculosis (TB) and during the COVID-19 pandemic, the global rate of TB-related deaths has increased for the first time in over a decade. We and others have previously shown that a resolved prior or ...

Abstract	Viral co-infections have been implicated in worsening tuberculosis (TB) and during the COVID-19 pandemic, the global rate of TB-related deaths has increased for the first time in over a decade. We and others have previously shown that a resolved prior or concurrent influenza A virus infection in
MeSH term(s)	Mice ; Animals ; Humans ; Mycobacterium tuberculosis ; SARS-CoV-2 ; Coinfection ; Pandemics ; COVID-19 ; Mice, Transgenic ; Interferon Type I ; Mice, Inbred C57BL
Chemical Substances	K-18 conjugate ; Interferon Type I
Language	English
Publishing date	2023-09-01
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Intramural
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2023.1240419
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Article ; Online: Toward an Effective Ebola Virus Vaccine.

Keshwara, Rohan / Johnson, Reed F / Schnell, Matthias J

Annual review of medicine

2017 Volume 68, Page(s) 371–386

Abstract: Long-term control of viral outbreaks requires the use of vaccines to impart acquired resistance and ensuing protection. In the wake of an epidemic, established immunity against a particular disease can limit spread and significantly decrease mortality. ... ...

Abstract	Long-term control of viral outbreaks requires the use of vaccines to impart acquired resistance and ensuing protection. In the wake of an epidemic, established immunity against a particular disease can limit spread and significantly decrease mortality. Creation of a safe and efficacious vaccine against Ebola virus (EBOV) has proven elusive so far, but various inventive strategies are now being employed to counteract the threat of outbreaks caused by EBOV and related filoviruses. Here, we present a current overview of progress in the field of Ebola virus vaccine development.
Language	English
Publishing date	2017-01-14
Publishing country	United States
Document type	Journal Article
ZDB-ID	207930-6
ISSN	1545-326X ; 0066-4219
ISSN (online)	1545-326X
ISSN	0066-4219
DOI	10.1146/annurev-med-051215-030919
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Article: The inflammatory microenvironment of the lung at the time of infection governs innate control of SARS-CoV-2 replication.

Baker, Paul J / Bohrer, Andrea C / Castro, Ehydel / Amaral, Eduardo P / Snow-Smith, Maryonne / Torres-Juárez, Flor / Gould, Sydnee T / Queiroz, Artur T L / Fukutani, Eduardo R / Jordan, Cassandra M / Khillan, Jaspal S / Cho, Kyoungin / Barber, Daniel L / Andrade, Bruno B / Johnson, Reed F / Hilligan, Kerry L / Mayer-Barber, Katrin D

bioRxiv : the preprint server for biology

2024

Abstract: SARS-CoV-2 infection leads to vastly divergent clinical outcomes ranging from asymptomatic infection to fatal disease. Co-morbidities, sex, age, host genetics and vaccine status are known to affect disease severity. Yet, how the inflammatory milieu of ... ...

Abstract	SARS-CoV-2 infection leads to vastly divergent clinical outcomes ranging from asymptomatic infection to fatal disease. Co-morbidities, sex, age, host genetics and vaccine status are known to affect disease severity. Yet, how the inflammatory milieu of the lung at the time of SARS-CoV-2 exposure impacts the control of viral replication remains poorly understood. We demonstrate here that immune events in the mouse lung closely preceding SARS-CoV-2 infection significantly impact viral control and we identify key innate immune pathways required to limit viral replication. A diverse set of pulmonary inflammatory stimuli, including resolved antecedent respiratory infections with
Language	English
Publishing date	2024-03-27
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.03.27.586885
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Article ; Online: Intranasal murine pneumonia virus-vectored SARS-CoV-2 vaccine induces mucosal and serum antibodies in macaques.

Kaiser, Jaclyn A / Liu, Xueqiao / Luongo, Cindy / Matsuoka, Yumiko / Santos, Celia / Yang, Lijuan / Herbert, Richard / Castens, Ashley / Dorward, David W / Johnson, Reed F / Park, Hong-Su / Afroz, Sharmin / Munir, Shirin / Le Nouën, Cyril / Buchholz, Ursula J

iScience

2023 Volume 26, Issue 12, Page(s) 108490

Abstract: Next-generation SARS-CoV-2 vaccines are needed that induce systemic and mucosal immunity. Murine pneumonia virus (MPV), a murine homolog of respiratory syncytial virus, is attenuated by host-range restriction in nonhuman primates and has a tropism for ... ...

Abstract	Next-generation SARS-CoV-2 vaccines are needed that induce systemic and mucosal immunity. Murine pneumonia virus (MPV), a murine homolog of respiratory syncytial virus, is attenuated by host-range restriction in nonhuman primates and has a tropism for the respiratory tract. We generated MPV vectors expressing the wild-type SARS-CoV-2 spike protein (MPV/S) or its prefusion-stabilized form (MPV/S-2P). Both vectors replicated similarly in cell culture and stably expressed S. However, only S-2P was associated with MPV particles. After intranasal/intratracheal immunization of rhesus macaques, MPV/S and MPV/S-2P replicated to low levels in the airways. Despite its low-level replication, MPV/S-2P induced high levels of mucosal and serum IgG and IgA to SARS-CoV-2 S or its receptor-binding domain. Serum antibodies from MPV/S-2P-immunized animals efficiently inhibited ACE2 receptor binding to S proteins of variants of concern. Based on its attenuation and immunogenicity in macaques, MPV/S-2P will be further evaluated as a live-attenuated vaccine for intranasal immunization against SARS-CoV-2.
Language	English
Publishing date	2023-11-22
Publishing country	United States
Document type	Journal Article
ISSN	2589-0042
ISSN (online)	2589-0042
DOI	10.1016/j.isci.2023.108490
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Article ; Online: Exposure to lung-migrating helminth protects against murine SARS-CoV-2 infection through macrophage-dependent T cell activation.

Oyesola, Oyebola O / Hilligan, Kerry L / Namasivayam, Sivaranjani / Howard, Nina / Clancy, Chad S / Zhao, Mingming / Oland, Sandra D / Kiwanuka, Kasalina N / Garza, Nicole L / Lafont, Bernard A P / Johnson, Reed F / Mayer-Barber, Katrin D / Sher, Alan / Loke, P'ng

Science immunology

2023 Volume 8, Issue 86, Page(s) eadf8161

Abstract: Helminth endemic regions report lower COVID-19 morbidity and mortality. Here, we show that lung remodeling from a prior infection with a lung-migrating helminth, ...

Abstract	Helminth endemic regions report lower COVID-19 morbidity and mortality. Here, we show that lung remodeling from a prior infection with a lung-migrating helminth,
MeSH term(s)	Mice ; Humans ; Animals ; CD8-Positive T-Lymphocytes ; COVID-19/metabolism ; SARS-CoV-2 ; Macrophages ; Lung ; Mice, Transgenic
Language	English
Publishing date	2023-08-11
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
ISSN	2470-9468
ISSN (online)	2470-9468
DOI	10.1126/sciimmunol.adf8161
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