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Article ; Online: Pathogenicity and virulence of henipaviruses.

Kaza, Benjamin / Aguilar, Hector C

2023 Volume 14, Issue 1, Page(s) 2273684

Abstract: Paramyxoviruses are a family of single-stranded negative-sense RNA viruses, many of which are responsible for a range of respiratory and neurological diseases in humans and animals. Among the most notable are the henipaviruses, which include the deadly ... ...

Abstract	Paramyxoviruses are a family of single-stranded negative-sense RNA viruses, many of which are responsible for a range of respiratory and neurological diseases in humans and animals. Among the most notable are the henipaviruses, which include the deadly Nipah (NiV) and Hendra (HeV) viruses, the causative agents of outbreaks of severe disease and high case fatality rates in humans and animals. NiV and HeV are maintained in fruit bat reservoirs primarily in the family
MeSH term(s)	Animals ; Humans ; Swine ; Horses ; Virulence ; Henipavirus Infections/epidemiology ; Henipavirus Infections/veterinary ; Nipah Virus/genetics ; Hendra Virus/genetics ; Disease Outbreaks ; Chiroptera
Language	English
Publishing date	2023-11-10
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural
ZDB-ID	2657572-3
ISSN	2150-5608 ; 2150-5594
ISSN (online)	2150-5608
ISSN	2150-5594
DOI	10.1080/21505594.2023.2273684
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Article ; Online: Cell-Cell Fusion Assays to Study Henipavirus Entry and Evaluate Therapeutics.

Monreal, I Abrrey / Aguilar, Hector C

Methods in molecular biology (Clifton, N.J.)

2023 Volume 2682, Page(s) 59–69

Abstract: Henipaviruses include the deadly zoonotic Nipah (NiV) and Hendra (HeV) paramyxoviruses, which have caused recurring outbreaks in human populations. A hallmark of henipavirus infection is the induction of cell-cell fusion (syncytia), caused by the ... ...

Abstract	Henipaviruses include the deadly zoonotic Nipah (NiV) and Hendra (HeV) paramyxoviruses, which have caused recurring outbreaks in human populations. A hallmark of henipavirus infection is the induction of cell-cell fusion (syncytia), caused by the expression of the attachment (G) and fusion (F) glycoproteins on the surface of infected cells. The interactions of G and F with each other and with receptors on cellular plasma membranes drive both viral entry and syncytia formation and are thus of great interest. While F shares structural and functional homologies with class I fusion proteins of other viruses such as influenza and human immunodeficiency viruses, the intricate interactions between the G and F glycoproteins allow for unique approaches to studying the class I membrane fusion process. This allows us to study cell-cell fusion and viral entry kinetics for BSL-4 pathogens such as NiV and HeV under BSL-2 conditions using recombinant DNA techniques. Here, we present approaches to studying henipavirus-induced membrane fusion for currently identified and emerging henipaviruses, including more traditional syncytia counting-based cell-cell fusion assay and a new heterologous fluorescent dye exchange cell-cell fusion assay.
MeSH term(s)	Henipavirus ; Virus Internalization ; Cell Fusion ; Humans
Language	English
Publishing date	2023-08-23
Publishing country	United States
Document type	Journal Article
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-0716-3283-3_4
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Article ; Online: Finding proteases that make cells go viral.

Aguilar, Hector C / Buchholz, David W

The Journal of biological chemistry

2020 Volume 295, Issue 33, Page(s) 11408–11409

Abstract: The activation of influenza virus hemagglutinin (HA) glycoprotein via cleavage by host cell proteases is essential for viral infectivity, and understanding the mechanisms for HA protein cleavage and how they may differ depending on the biological context ...

Abstract	The activation of influenza virus hemagglutinin (HA) glycoprotein via cleavage by host cell proteases is essential for viral infectivity, and understanding the mechanisms for HA protein cleavage and how they may differ depending on the biological context is important for the development of flu treatments. However, the HA proteases involved in the activation of many viral strains remain unidentified. In this issue, Harbig
MeSH term(s)	Animals ; Gene Expression Profiling ; Hemagglutinin Glycoproteins, Influenza Virus ; Influenza A Virus, H3N2 Subtype ; Influenza B virus ; Influenza, Human ; Mice ; Peptide Hydrolases
Chemical Substances	Hemagglutinin Glycoproteins, Influenza Virus ; Peptide Hydrolases (EC 3.4.-)
Language	English
Publishing date	2020-08-08
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Comment
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1074/jbc.H120.015153
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Article ; Online: Feline Morbillivirus, a New Paramyxovirus Possibly Associated with Feline Kidney Disease.

Choi, Eun Jin / Ortega, Victoria / Aguilar, Hector C

Viruses

2020 Volume 12, Issue 5

Abstract: Feline morbillivirus (FeMV) was first isolated in stray cats in Hong Kong in 2012. Since its discovery, the virus has been reported in domestic cats worldwide, including in Hong Kong, Japan, Italy, US, Brazil, Turkey, UK, Germany, and Malaysia. FeMV is ... ...

Abstract	Feline morbillivirus (FeMV) was first isolated in stray cats in Hong Kong in 2012. Since its discovery, the virus has been reported in domestic cats worldwide, including in Hong Kong, Japan, Italy, US, Brazil, Turkey, UK, Germany, and Malaysia. FeMV is classified in the
MeSH term(s)	Animals ; Cat Diseases/virology ; Cats ; Kidney Diseases/veterinary ; Kidney Diseases/virology ; Morbillivirus/classification ; Morbillivirus/genetics ; Morbillivirus/isolation & purification ; Morbillivirus Infections/veterinary ; Morbillivirus Infections/virology ; Paramyxoviridae/classification ; Paramyxoviridae/genetics ; Paramyxoviridae/isolation & purification
Keywords	covid19
Language	English
Publishing date	2020-05-01
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v12050501
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Article ; Online: The Human Gut Virome and Its Relationship with Nontransmissible Chronic Diseases.

Ezzatpour, Shahrzad / Mondragon Portocarrero, Alicia Del Carmen / Cardelle-Cobas, Alejandra / Lamas, Alexandre / López-Santamarina, Aroa / Miranda, José Manuel / Aguilar, Hector C

Nutrients

2023 Volume 15, Issue 4

Abstract: The human gastrointestinal tract contains large communities of microorganisms that are in constant interaction with the host, playing an essential role in the regulation of several metabolic processes. Among the gut microbial communities, the gut ... ...

Abstract	The human gastrointestinal tract contains large communities of microorganisms that are in constant interaction with the host, playing an essential role in the regulation of several metabolic processes. Among the gut microbial communities, the gut bacteriome has been most widely studied in recent decades. However, in recent years, there has been increasing interest in studying the influences that other microbial groups can exert on the host. Among them, the gut virome is attracting great interest because viruses can interact with the host immune system and metabolic functions; this is also the case for phages, which interact with the bacterial microbiota. The antecedents of virome-rectification-based therapies among various diseases were also investigated. In the near future, stool metagenomic investigation should include the identification of bacteria and phages, as well as their correlation networks, to better understand gut microbiota activity in metabolic disease progression.
MeSH term(s)	Humans ; Virome ; Viruses/metabolism ; Bacteriophages ; Microbiota ; Gastrointestinal Microbiome
Language	English
Publishing date	2023-02-15
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2518386-2
ISSN	2072-6643 ; 2072-6643
ISSN (online)	2072-6643
ISSN	2072-6643
DOI	10.3390/nu15040977
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Article ; Online: Characterization of the cellular lipid composition during SARS-CoV-2 infection.

Abdel-Megied, Ahmed M / Monreal, Isaac A / Zhao, Limian / Apffel, Alex / Aguilar, Hector C / Jones, Jace W

Analytical and bioanalytical chemistry

2023 Volume 415, Issue 22, Page(s) 5269–5279

Abstract: Emerging and re-emerging zoonotic viral diseases continue to significantly impact public health. Of particular interest are enveloped viruses (e.g., SARS-CoV-2, the causative pathogen of COVID-19), which include emerging pathogens of highest concern. ... ...

Abstract	Emerging and re-emerging zoonotic viral diseases continue to significantly impact public health. Of particular interest are enveloped viruses (e.g., SARS-CoV-2, the causative pathogen of COVID-19), which include emerging pathogens of highest concern. Enveloped viruses contain a viral envelope that encapsulates the genetic material and nucleocapsid, providing structural protection and functional bioactivity. The viral envelope is composed of a coordinated network of glycoproteins and lipids. The lipid composition of the envelope consists of lipids preferentially appropriated from host cell membranes. Subsequently, changes to the host cell lipid metabolism and an accounting of what lipids are changed during viral infection provide an opportunity to fingerprint the host cell's response to the infecting virus. To address this issue, we comprehensively characterized the lipid composition of VeroE6-TMPRSS2 cells infected with SARS-CoV-2. Our approach involved using an innovative solid-phase extraction technique to efficiently extract cellular lipids combined with liquid chromatography coupled to high-resolution tandem mass spectrometry. We identified lipid changes in cells exposed to SARS-CoV-2, of which the ceramide to sphingomyelin ratio was most prominent. The identification of a lipid profile (i.e., lipid fingerprint) that is characteristic of cellular SARS-CoV-2 infection lays the foundation for targeting lipid metabolism pathways to further understand how enveloped viruses infect cells, identifying opportunities to aid antiviral and vaccine development.
MeSH term(s)	Humans ; COVID-19 ; SARS-CoV-2 ; Lipids
Chemical Substances	Lipids
Language	English
Publishing date	2023-07-13
Publishing country	Germany
Document type	Journal Article
ZDB-ID	201093-8
ISSN	1618-2650 ; 0016-1152 ; 0372-7920
ISSN (online)	1618-2650
ISSN	0016-1152 ; 0372-7920
DOI	10.1007/s00216-023-04825-1
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Article: Migraine inhibitor olcegepant reduces weight loss and IL-6 release in SARS-CoV-2 infected older mice with neurological signs.

Rahman, Shafaqat M / Buchholz, David W / Imbiakha, Brian / Jaeger, Mason C / Leach, Justin / Osborn, Raven M / Birmingham, Ann O / Dewhurst, Stephen / Aguilar, Hector C / Luebke, Anne E

bioRxiv : the preprint server for biology

2024

Abstract: COVID-19 can result in neurological symptoms such as fever, headache, dizziness, and nausea. However, neurological signs of SARS-CoV-2 infection have been hardly assessed in mouse models. Here, we infected two commonly used wildtype mice lines (C57BL/6 ... ...

Abstract	COVID-19 can result in neurological symptoms such as fever, headache, dizziness, and nausea. However, neurological signs of SARS-CoV-2 infection have been hardly assessed in mouse models. Here, we infected two commonly used wildtype mice lines (C57BL/6 and 129S) with mouse-adapted SARS-CoV-2 and demonstrated neurological signs including motion-related dizziness. We then evaluated whether the Calcitonin Gene-Related Peptide (CGRP) receptor antagonist, olcegepant, used in migraine treatment could mitigate acute neuroinflammatory and neurological responses to SARS-COV-2 infection. We infected wildtype C57BL/6J and 129/SvEv mice, and a 129 αCGRP-null mouse line with a mouse-adapted SARS-CoV-2 virus, and evaluated the effect of CGRP receptor antagonism on the outcome of that infection. First, we determined that CGRP receptor antagonism provided protection from permanent weight loss in older (>12 m) C57BL/6J and 129 SvEv mice. We also observed acute fever and motion-induced dizziness in all older mice, regardless of treatment. However, in both wildtype mouse lines, CGRP antagonism reduced acute interleukin 6 (IL-6) levels by half, with virtually no IL-6 release in mice lacking αCGRP. These findings suggest that migraine inhibitors such as those blocking CGRP signaling protect against acute IL-6 release and subsequent inflammatory events after SARS-CoV-2 infection, which may have repercussions for related pandemic and/or endemic coronaviruses.
Language	English
Publishing date	2024-01-23
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.10.23.563669
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Article ; Online: Rapid Detection of Viral Envelope Lipids Using Lithium Adducts and AP-MALDI High-Resolution Mass Spectrometry.

Tran, Anh / Monreal, I Abrrey / Moskovets, Eugene / Aguilar, Hector C / Jones, Jace W

Journal of the American Society for Mass Spectrometry

2021 Volume 32, Issue 9, Page(s) 2322–2333

Abstract: There is an unmet need to develop analytical strategies that not only characterize the lipid composition of the viral envelope but also do so on a time scale that would allow for high-throughput analysis. With that in mind, we report the use of ... ...

Abstract	There is an unmet need to develop analytical strategies that not only characterize the lipid composition of the viral envelope but also do so on a time scale that would allow for high-throughput analysis. With that in mind, we report the use of atmospheric pressure (AP) matrix-assisted laser desorption/ionization (MALDI) high-resolution mass spectrometry (HRMS) combined with lithium adduct consolidation to profile total lipid extracts rapidly and confidently from enveloped viruses. The use of AP-MALDI reduced the dependency of using a dedicated MALDI mass spectrometer and allowed for interfacing the MALDI source to a mass spectrometer with the desired features, which included high mass resolving power (>100000) and tandem mass spectrometry. AP-MALDI combined with an optimized MALDI matrix system, featuring 2',4',6'-trihydroxyacetophenone spiked with lithium salt, resulted in a robust and high-throughput lipid detection platform, specifically geared to sphingolipid detection. Application of the developed workflow included the structural characterization of prominent sphingolipids and detection of over 130 lipid structures from Influenza A virions. Overall, we demonstrate a high-throughput workflow for the detection and structural characterization of total lipid extracts from enveloped viruses using AP-MALDI HRMS and lithium adduct consolidation.
MeSH term(s)	Lithium/chemistry ; Membrane Lipids/analysis ; Membrane Lipids/chemistry ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methods ; Sphingolipids/analysis ; Sphingolipids/chemistry
Chemical Substances	Membrane Lipids ; Sphingolipids ; viral envelope lipids ; Lithium (9FN79X2M3F)
Language	English
Publishing date	2021-04-22
Publishing country	United States
Document type	Journal Article
ZDB-ID	1073671-2
ISSN	1879-1123 ; 1044-0305
ISSN (online)	1879-1123
ISSN	1044-0305
DOI	10.1021/jasms.1c00058
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Article ; Online: Headless Henipaviral Receptor Binding Glycoproteins Reveal Fusion Modulation by the Head/Stalk Interface and Post-receptor Binding Contributions of the Head Domain.

Yeo, Yao Yu / Buchholz, David W / Gamble, Amandine / Jager, Mason / Aguilar, Hector C

Journal of virology

2021 Volume 95, Issue 20, Page(s) e0066621

Abstract: Cedar virus (CedV) is a nonpathogenic member of ... ...

Abstract	Cedar virus (CedV) is a nonpathogenic member of the
MeSH term(s)	Giant Cells/metabolism ; Glycoproteins/genetics ; HEK293 Cells ; Henipavirus/genetics ; Henipavirus/metabolism ; Henipavirus Infections/metabolism ; Henipavirus Infections/virology ; Humans ; Membrane Fusion/physiology ; Receptors, Virus/metabolism ; Viral Envelope Proteins/genetics ; Viral Fusion Proteins/genetics ; Viral Fusion Proteins/metabolism ; Viral Fusion Proteins/physiology ; Virus Attachment ; Virus Internalization
Chemical Substances	Glycoproteins ; Receptors, Virus ; Viral Envelope Proteins ; Viral Fusion Proteins
Language	English
Publishing date	2021-07-21
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	80174-4
ISSN	1098-5514 ; 0022-538X
ISSN (online)	1098-5514
ISSN	0022-538X
DOI	10.1128/JVI.00666-21
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Article ; Online: Novel Roles of the N1 Loop and N4 Alpha-Helical Region of the Nipah Virus Fusion Glycoprotein in Modulating Early and Late Steps of the Membrane Fusion Cascade.

Zamora, J Lizbeth Reyes / Ortega, Victoria / Johnston, Gunner P / Li, Jenny / Aguilar, Hector C

Journal of virology

2021 Volume 95, Issue 9

Abstract: Nipah virus (NiV) is a zoonotic bat henipavirus in the ... ...

Abstract	Nipah virus (NiV) is a zoonotic bat henipavirus in the family
MeSH term(s)	Animals ; Chlorocebus aethiops ; HEK293 Cells ; Henipavirus Infections/virology ; Humans ; Membrane Fusion ; Nipah Virus/physiology ; Protein Conformation ; Protein Conformation, alpha-Helical ; Vero Cells ; Viral Fusion Proteins/chemistry ; Virus Internalization
Chemical Substances	Viral Fusion Proteins
Language	English
Publishing date	2021-04-12
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	80174-4
ISSN	1098-5514 ; 0022-538X
ISSN (online)	1098-5514
ISSN	0022-538X
DOI	10.1128/JVI.01707-20
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