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Article ; Online: Alphavirus Particles Can Assemble with an Alternate Triangulation Number.

Kaelber, Jason T / Chmielewski, David / Chiu, Wah / Auguste, Albert J

2022 Volume 14, Issue 12

Abstract: Alphaviruses are spherical, enveloped RNA viruses primarily transmitted by mosquitoes, and cause significant arthritogenic and neurotropic disease in humans and livestock. Previous reports have shown that-in contrast to prototypical icosahedral viruses- ... ...

Abstract	Alphaviruses are spherical, enveloped RNA viruses primarily transmitted by mosquitoes, and cause significant arthritogenic and neurotropic disease in humans and livestock. Previous reports have shown that-in contrast to prototypical icosahedral viruses-alphaviruses incorporate frequent defects, and these may serve important functions in the viral life cycle. We confirm the genus-wide pleomorphism in live viral particles and extend our understanding of alphavirus assembly through the discovery of an alternate architecture of Eastern equine encephalitis virus (EEEV) particles. The alternate
MeSH term(s)	Alphavirus/genetics ; Capsid Proteins/genetics ; Encephalitis Virus, Eastern Equine/genetics ; Virion/genetics
Chemical Substances	Capsid Proteins
Language	English
Publishing date	2022-11-27
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v14122650
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Article ; Online: Cryogenic electron microscopy and tomography reveal imperfect icosahedral symmetry in alphaviruses.

Chmielewski, David / Su, Guan-Chin / Kaelber, Jason T / Pintilie, Grigore D / Chen, Muyuan / Jin, Jing / Auguste, Albert J / Chiu, Wah

PNAS nexus

2024 Volume 3, Issue 3, Page(s) pgae102

Abstract: Alphaviruses are spherical, enveloped RNA viruses with two-layered icosahedral architecture. The structures of many alphaviruses have been studied using cryogenic electron microscopy (cryo-EM) reconstructions, which impose icosahedral symmetry on the ... ...

Abstract	Alphaviruses are spherical, enveloped RNA viruses with two-layered icosahedral architecture. The structures of many alphaviruses have been studied using cryogenic electron microscopy (cryo-EM) reconstructions, which impose icosahedral symmetry on the viral particles. Using cryogenic electron tomography (cryo-ET), we revealed a polarized symmetry defect in the icosahedral lattice of Chikungunya virus (CHIKV) in situ, similar to the late budding particles, suggesting the inherent imperfect symmetry originates from the final pinch-off of assembled virions. We further demonstrated this imperfect symmetry is also present in in vitro purified CHIKV and Mayaro virus, another arthritogenic alphavirus. We employed a subparticle-based single-particle analysis protocol to circumvent the icosahedral imperfection and boosted the resolution of the structure of the CHIKV to ∼3 Å resolution, which revealed detailed molecular interactions between glycoprotein E1-E2 heterodimers in the transmembrane region and multiple lipid-like pocket factors located in a highly conserved hydrophobic pocket. This complementary use of in situ cryo-ET and single-particle cryo-EM approaches provides a more precise structural description of near-icosahedral viruses and valuable insights to guide the development of structure-based antiviral therapies against alphaviruses.
Language	English
Publishing date	2024-03-07
Publishing country	England
Document type	Journal Article
ISSN	2752-6542
ISSN (online)	2752-6542
DOI	10.1093/pnasnexus/pgae102
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Article ; Online: Transmission risk of Oropouche fever across the Americas.

Romero-Alvarez, Daniel / Escobar, Luis E / Auguste, Albert J / Del Valle, Sara Y / Manore, Carrie A

Infectious diseases of poverty

2023 Volume 12, Issue 1, Page(s) 47

Abstract: Background: Vector-borne diseases (VBDs) are important contributors to the global burden of infectious diseases due to their epidemic potential, which can result in significant population and economic impacts. Oropouche fever, caused by Oropouche virus ( ...

Abstract	Background: Vector-borne diseases (VBDs) are important contributors to the global burden of infectious diseases due to their epidemic potential, which can result in significant population and economic impacts. Oropouche fever, caused by Oropouche virus (OROV), is an understudied zoonotic VBD febrile illness reported in Central and South America. The epidemic potential and areas of likely OROV spread remain unexplored, limiting capacities to improve epidemiological surveillance. Methods: To better understand the capacity for spread of OROV, we developed spatial epidemiology models using human outbreaks as OROV transmission-locality data, coupled with high-resolution satellite-derived vegetation phenology. Data were integrated using hypervolume modeling to infer likely areas of OROV transmission and emergence across the Americas. Results: Models based on one-support vector machine hypervolumes consistently predicted risk areas for OROV transmission across the tropics of Latin America despite the inclusion of different parameters such as different study areas and environmental predictors. Models estimate that up to 5 million people are at risk of exposure to OROV. Nevertheless, the limited epidemiological data available generates uncertainty in projections. For example, some outbreaks have occurred under climatic conditions outside those where most transmission events occur. The distribution models also revealed that landscape variation, expressed as vegetation loss, is linked to OROV outbreaks. Conclusions: Hotspots of OROV transmission risk were detected along the tropics of South America. Vegetation loss might be a driver of Oropouche fever emergence. Modeling based on hypervolumes in spatial epidemiology might be considered an exploratory tool for analyzing data-limited emerging infectious diseases for which little understanding exists on their sylvatic cycles. OROV transmission risk maps can be used to improve surveillance, investigate OROV ecology and epidemiology, and inform early detection.
MeSH term(s)	Humans ; Bunyaviridae Infections/epidemiology ; Orthobunyavirus ; Disease Outbreaks ; Americas
Language	English
Publishing date	2023-05-06
Publishing country	England
Document type	Journal Article
ZDB-ID	2689396-4
ISSN	2049-9957 ; 2049-9957
ISSN (online)	2049-9957
ISSN	2049-9957
DOI	10.1186/s40249-023-01091-2
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Article ; Online: The influence of SARS-CoV-2 infection on expression of drug-metabolizing enzymes and transporters in a hACE2 murine model.

Deshpande, Kiran / Lange, Keith R / Stone, William B / Yohn, Christine / Schlesinger, Naomi / Kagan, Leonid / Auguste, Albert J / Firestein, Bonnie L / Brunetti, Luigi

Pharmacology research & perspectives

2023 Volume 11, Issue 3, Page(s) e01071

Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the resulting Coronavirus disease 2019 emerged in late 2019 and is responsible for significant morbidity and mortality worldwide. A hallmark of severe COVID-19 is exaggerated ... ...

Abstract	Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the resulting Coronavirus disease 2019 emerged in late 2019 and is responsible for significant morbidity and mortality worldwide. A hallmark of severe COVID-19 is exaggerated systemic inflammation, regarded as a "cytokine storm," which contributes to the damage of various organs, primarily the lungs. The inflammation associated with some viral illnesses is known to alter the expression of drug-metabolizing enzymes and transporters. These alterations can lead to modifications in drug exposure and the processing of various endogenous compounds. Here, we provide evidence to support changes in the mitochondrial ribonucleic acid expression of a subset of drug transporters (84 transporters) in the liver, kidneys, and lungs and metabolizing enzymes (84 enzymes) in the liver in a humanized angiotensin-converting enzyme 2 receptor mouse model. Specifically, three drug transporters (Abca3, Slc7a8, Tap1) and the pro-inflammatory cytokine IL-6 were upregulated in the lungs of SARS-CoV-2 infected mice. We also found significant downregulation of drug transporters responsible for the movement of xenobiotics in the liver and kidney. Additionally, expression of cytochrome P-450 2f2 which is known to metabolize some pulmonary toxicants, was significantly decreased in the liver of infected mice. The significance of these findings requires further exploration. Our results suggest that further research should emphasize altered drug disposition when investigating therapeutic compounds, whether re-purposed or new chemical entities, in other animal models and ultimately in individuals infected with SARS-CoV-2. Moreover, the influence and impact of these changes on the processing of endogenous compounds also require further investigation.
MeSH term(s)	Mice ; Animals ; COVID-19 ; SARS-CoV-2 ; Disease Models, Animal ; Peptidyl-Dipeptidase A/metabolism ; Inflammation
Chemical Substances	Peptidyl-Dipeptidase A (EC 3.4.15.1)
Language	English
Publishing date	2023-05-05
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2740389-0
ISSN	2052-1707 ; 2052-1707
ISSN (online)	2052-1707
ISSN	2052-1707
DOI	10.1002/prp2.1071
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Article ; Online: Phylogenetic characterization of Orthobunyaviruses isolated from Trinidad shows evidence of natural reassortment.

Foster, Jerome E / López, Krisangel / Eastwood, Gillian / Guzman, Hilda / Carrington, Christine V F / Tesh, Robert B / Auguste, Albert J

Virus genes

2023 Volume 59, Issue 3, Page(s) 473–478

Abstract: The genus Orthobunyavirus is a diverse group of viruses in the family Peribunyaviridae, recently classified into 20 serogroups, and 103 virus species. Although most viruses within these serogroups are phylogenetically distinct, the absence of complete ... ...

Abstract	The genus Orthobunyavirus is a diverse group of viruses in the family Peribunyaviridae, recently classified into 20 serogroups, and 103 virus species. Although most viruses within these serogroups are phylogenetically distinct, the absence of complete genome sequences has left several viruses incompletely characterized. Here we report the complete genome sequences for 11 orthobunyaviruses isolated from Trinidad, French Guiana, Guatemala, and Panama that were serologically classified into six serogroups and 10 species. Phylogenetic analyses of these 11 newly derived sequences indicate that viruses belonging to the Patois, Capim, Guama, and Group C serocomplexes all have a close genetic origin. We show that three of the 11 orthobunyaviruses characterized (belonging to the Group C and Bunyamwera serogroups) have evidence of histories of natural reassortment through the M genome segment. Our data also suggests that two distinct lineages of Group C viruses concurrently circulate in Trinidad and are transmitted by the same mosquito vectors. This study also highlights the importance of complementing serological identification with nucleotide sequencing when characterizing orthobunyaviruses.
MeSH term(s)	Animals ; Orthobunyavirus ; Phylogeny ; Serogroup ; Trinidad and Tobago ; Sequence Analysis, DNA ; Genome, Viral
Language	English
Publishing date	2023-02-10
Publishing country	United States
Document type	Journal Article
ZDB-ID	639496-6
ISSN	1572-994X ; 0920-8569
ISSN (online)	1572-994X
ISSN	0920-8569
DOI	10.1007/s11262-023-01973-5
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Zs.A 2397: Show issues

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Article ; Online: A bioengineered pseudovirus nanoparticle displaying SARS-CoV 2 RBD fully protects mice from mortality and weight loss caused by SARS-CoV 2 challenge.

Xia, Ming / López, Krisangel / Vago, Frank S / Huang, Pengwei / Auguste, Dawn I / Jiang, Wen / Auguste, Albert J / Tan, Ming

Biotechnology journal

2023 Volume 18, Issue 10, Page(s) e2300130

Abstract: The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused considerable morbidity and mortality worldwide. Although authorized COVID-19 vaccines have been shown highly effective, their significantly lower ... ...

Abstract	The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused considerable morbidity and mortality worldwide. Although authorized COVID-19 vaccines have been shown highly effective, their significantly lower efficacy against heterologous variants, and the rapid decrease of vaccine-elicited immunity raises serious concerns, calling for improved vaccine tactics. To this end, a pseudovirus nanoparticle (PVNP) displaying the receptor binding domains (RBDs) of SARS-CoV-2 spike, named S-RBD, was generated and shown it as a promising COVID-19 vaccine candidate. The S-RBD PVNP was produced using both prokaryotic and eukaryotic systems. A 3D structural model of the S-RBD PVNPs was built based on the known structures of the S
MeSH term(s)	Animals ; Humans ; Mice ; SARS-CoV-2/genetics ; COVID-19/prevention & control ; COVID-19 Vaccines/genetics ; Pandemics ; Weight Loss ; Nanoparticles
Chemical Substances	COVID-19 Vaccines
Language	English
Publishing date	2023-06-23
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2221885-3
ISSN	1860-7314 ; 1860-6768
ISSN (online)	1860-7314
ISSN	1860-6768
DOI	10.1002/biot.202300130
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Zs.A 6349: Show issues

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Article ; Online: Vector competence of Virginia mosquitoes for Zika and Cache Valley viruses.

Chan, Kevin K / Auguste, Albert J / Brewster, Carlyle C / Paulson, Sally L

Parasites & vectors

2020 Volume 13, Issue 1, Page(s) 188

Abstract: Background: Vector-borne diseases are a major public health concern and cause significant morbidity and mortality. Zika virus (ZIKV) is the etiologic agent of a massive outbreak in the Americas that originated in Brazil in 2015 and shows a strong ... ...

Abstract	Background: Vector-borne diseases are a major public health concern and cause significant morbidity and mortality. Zika virus (ZIKV) is the etiologic agent of a massive outbreak in the Americas that originated in Brazil in 2015 and shows a strong association with congenital ZIKV syndrome in newborns. Cache Valley virus (CVV) is a bunyavirus that causes mild to severe illness in humans and ruminants. In this study, we investigated the vector competence of Virginia mosquitoes for ZIKV and CVV to explore their abilities to contribute to potential outbreaks. Methods: To determine vector competence, mosquitoes were fed a blood meal comprised of defibrinated sheep blood and virus. The presence of midgut or salivary gland barriers to ZIKV infection were determined by intrathoracic inoculation vs oral infection. After 14-days post-exposure, individual mosquitoes were separated into bodies, legs and wings, and saliva expectorant. Virus presence was detected by plaque assay to determine midgut infection, dissemination, and transmission rates. Results: Transmission rates for Ae. albopictus orally infected (24%) and intrathoracically inoculated (63%) with ZIKV was similar to Ae. aegypti (48% and 71%, respectively). Transmission rates of ZIKV in Ae. japonicus were low, and showed evidence of a midgut infection barrier demonstrated by low midgut infection and dissemination rates from oral infection (3%), but increased transmission rates after intrathoracic inoculation (19%). Aedes triseriatus was unable to transmit ZIKV following oral infection or intrathoracic inoculation. CVV transmission was dose-dependent where mosquitoes fed high titer (ht) virus blood meals developed higher rates of midgut infection, dissemination, and transmission compared to low titer (lt) virus blood meals. CVV was detected in the saliva of Ae. albopictus (ht: 68%, lt: 24%), Ae. triseriatus (ht: 52%, lt: 7%), Ae. japonicus (ht: 22%, lt: 0%) and Ae. aegypti (ht: 10%; lt: 7%). Culex pipiens and Cx. restuans were not competent for ZIKV or CVV. Conclusions: This laboratory transmission study provided further understanding of potential ZIKV and CVV transmission cycles with Aedes mosquitoes from Virginia. The ability for these mosquitoes to transmit ZIKV and CVV make them a public health concern and suggest targeted control programs by mosquito and vector abatement districts.
MeSH term(s)	Aedes/virology ; Animals ; Biological Assay ; Blood/virology ; Bunyamwera virus/isolation & purification ; Bunyaviridae Infections/transmission ; Culex/virology ; Disease Vectors ; Humans ; Intestines/virology ; Mosquito Vectors/virology ; Saliva/virology ; United States ; Viral Load ; Virginia ; Zika Virus/isolation & purification ; Zika Virus Infection/transmission
Language	English
Publishing date	2020-04-10
Publishing country	England
Document type	Journal Article
ZDB-ID	2409480-8
ISSN	1756-3305 ; 1756-3305
ISSN (online)	1756-3305
ISSN	1756-3305
DOI	10.1186/s13071-020-04042-0
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Article: Vector competence of Virginia mosquitoes for Zika and Cache Valley viruses

Chan, Kevin K / Auguste, Albert J / Brewster, Carlyle C / Paulson, Sally L

Parasites & vectors. 2020 Dec., v. 13, no. 1

2020

Abstract: BACKGROUND: Vector-borne diseases are a major public health concern and cause significant morbidity and mortality. Zika virus (ZIKV) is the etiologic agent of a massive outbreak in the Americas that originated in Brazil in 2015 and shows a strong ... ...

Abstract	BACKGROUND: Vector-borne diseases are a major public health concern and cause significant morbidity and mortality. Zika virus (ZIKV) is the etiologic agent of a massive outbreak in the Americas that originated in Brazil in 2015 and shows a strong association with congenital ZIKV syndrome in newborns. Cache Valley virus (CVV) is a bunyavirus that causes mild to severe illness in humans and ruminants. In this study, we investigated the vector competence of Virginia mosquitoes for ZIKV and CVV to explore their abilities to contribute to potential outbreaks. METHODS: To determine vector competence, mosquitoes were fed a blood meal comprised of defibrinated sheep blood and virus. The presence of midgut or salivary gland barriers to ZIKV infection were determined by intrathoracic inoculation vs oral infection. After 14-days post-exposure, individual mosquitoes were separated into bodies, legs and wings, and saliva expectorant. Virus presence was detected by plaque assay to determine midgut infection, dissemination, and transmission rates. RESULTS: Transmission rates for Ae. albopictus orally infected (24%) and intrathoracically inoculated (63%) with ZIKV was similar to Ae. aegypti (48% and 71%, respectively). Transmission rates of ZIKV in Ae. japonicus were low, and showed evidence of a midgut infection barrier demonstrated by low midgut infection and dissemination rates from oral infection (3%), but increased transmission rates after intrathoracic inoculation (19%). Aedes triseriatus was unable to transmit ZIKV following oral infection or intrathoracic inoculation. CVV transmission was dose-dependent where mosquitoes fed high titer (ht) virus blood meals developed higher rates of midgut infection, dissemination, and transmission compared to low titer (lt) virus blood meals. CVV was detected in the saliva of Ae. albopictus (ht: 68%, lt: 24%), Ae. triseriatus (ht: 52%, lt: 7%), Ae. japonicus (ht: 22%, lt: 0%) and Ae. aegypti (ht: 10%; lt: 7%). Culex pipiens and Cx. restuans were not competent for ZIKV or CVV. CONCLUSIONS: This laboratory transmission study provided further understanding of potential ZIKV and CVV transmission cycles with Aedes mosquitoes from Virginia. The ability for these mosquitoes to transmit ZIKV and CVV make them a public health concern and suggest targeted control programs by mosquito and vector abatement districts.
Keywords	Aedes aegypti ; Aedes albopictus ; Aedes triseriatus ; Bunyamwera orthobunyavirus ; Culex pipiens ; Ochlerotatus japonicus ; Zika virus ; blood ; blood meal ; disease severity ; dose response ; etiological agents ; humans ; legs ; midgut ; morbidity ; mortality ; neonates ; public health ; saliva ; salivary glands ; sheep ; vector competence ; vector-borne diseases ; viruses ; wings ; Brazil ; Virginia
Language	English
Dates of publication	2020-12
Size	p. 188.
Publishing place	BioMed Central
Document type	Article
ZDB-ID	2409480-8
ISSN	1756-3305
ISSN	1756-3305
DOI	10.1186/s13071-020-04042-0
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Article ; Online: Arrangement of the Polymerase Complexes inside a Nine-Segmented dsRNA Virus

Kaelber, Jason T. / Jiang, Wen / Weaver, Scott C. / Auguste, Albert J. / Chiu, Wah

Structure 2020 Jun 2., v.28, no.6, p. 604-612.ed3.

2020 , Page(s) 604–612

Abstract: Members of the family Reoviridae package several copies of the viral polymerase complex into their capsid to carry out replication and transcription within viral particles. Classical single-particle reconstruction encounters difficulties resolving ... ...

Abstract	Members of the family Reoviridae package several copies of the viral polymerase complex into their capsid to carry out replication and transcription within viral particles. Classical single-particle reconstruction encounters difficulties resolving structures such as the intraparticle polymerase complex because refinement can converge to an incorrect map and because the map could depict a nonrepresentative subset of particles or an average of heterogeneous particles. Using the nine-segmented Fako virus, we tested hypotheses for the arrangement and number of polymerase complexes within the virion by measuring how well each hypothesis describes the set of cryoelectron microscopy images of individual viral particles. We find that the polymerase complex in Fako virus binds at ten possible sites despite having only nine genome segments. A single asymmetric configuration describes the arrangement of these complexes in both virions and genome-free capsids. Similarities between the arrangements of Reoviridae with 9, 10, and 11 segments indicate the generalizability of this architecture.
Keywords	Reoviridae ; capsid ; cryo-electron microscopy ; genome ; virion ; viruses
Language	English
Dates of publication	2020-06
Size	p. 604-612.e3
Publishing place	Elsevier Ltd.
Document type	Article ; Online
Note	Resource is Open Access ; CHORUS License Information
ZDB-ID	1213087-4
ISSN	1878-4186 ; 0969-2126
ISSN (online)	1878-4186
ISSN	0969-2126
DOI	10.1016/j.str.2020.01.011
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Article ; Online: Arrangement of the Polymerase Complexes inside a Nine-Segmented dsRNA Virus.

Kaelber, Jason T / Jiang, Wen / Weaver, Scott C / Auguste, Albert J / Chiu, Wah

Structure (London, England : 1993)

2020 Volume 28, Issue 6, Page(s) 604–612.e3

Abstract	Members of the family Reoviridae package several copies of the viral polymerase complex into their capsid to carry out replication and transcription within viral particles. Classical single-particle reconstruction encounters difficulties resolving structures such as the intraparticle polymerase complex because refinement can converge to an incorrect map and because the map could depict a nonrepresentative subset of particles or an average of heterogeneous particles. Using the nine-segmented Fako virus, we tested hypotheses for the arrangement and number of polymerase complexes within the virion by measuring how well each hypothesis describes the set of cryoelectron microscopy images of individual viral particles. We find that the polymerase complex in Fako virus binds at ten possible sites despite having only nine genome segments. A single asymmetric configuration describes the arrangement of these complexes in both virions and genome-free capsids. Similarities between the arrangements of Reoviridae with 9, 10, and 11 segments indicate the generalizability of this architecture.
MeSH term(s)	Animals ; Cell Line ; Cryoelectron Microscopy ; DNA-Directed RNA Polymerases/chemistry ; DNA-Directed RNA Polymerases/metabolism ; Models, Molecular ; Nucleoside-Triphosphatase/chemistry ; Nucleoside-Triphosphatase/metabolism ; Protein Conformation ; Reoviridae/chemistry ; Reoviridae/ultrastructure ; Viral Proteins/chemistry ; Viral Proteins/genetics ; Viral Proteins/metabolism
Chemical Substances	Viral Proteins ; DNA-Directed RNA Polymerases (EC 2.7.7.6) ; Nucleoside-Triphosphatase (EC 3.6.1.15)
Language	English
Publishing date	2020-02-10
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1213087-4
ISSN	1878-4186 ; 0969-2126
ISSN (online)	1878-4186
ISSN	0969-2126
DOI	10.1016/j.str.2020.01.011
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