A5016107911- Viral Infections and Outbreaks Research
- Viral Infections and Vectors
- SARS-CoV-2 and COVID-19 Research
- Hepatitis B Virus Studies
- Virology and Viral Diseases
- Viral gastroenteritis research and epidemiology
- Virus-based gene therapy research
- Animal Virus Infections Studies
- Influenza Virus Research Studies
- COVID-19 Clinical Research Studies
- SARS-CoV-2 detection and testing
- RNA modifications and cancer
- Bacillus and Francisella bacterial research
- Disaster Response and Management
- interferon and immune responses
- Metabolism and Genetic Disorders
- Toxin Mechanisms and Immunotoxins
- Mitochondrial Function and Pathology
- Global Security and Public Health
- Cytomegalovirus and herpesvirus research
- Plant Virus Research Studies
- Plant Taxonomy and Phylogenetics
- Respiratory viral infections research
- Vector-Borne Animal Diseases
- Animal Disease Management and Epidemiology
National Institute of Allergy and Infectious Diseases
2013-2024
National Institutes of Health
2013-2024
University of Hawaiʻi at Mānoa
2017
Academy of Military Medical Sciences
2016
Nipah virus is a highly lethal zoonotic paramyxovirus that was first recognized in Malaysia during an outbreak 1998. During this outbreak, infection caused severe febrile neurological disease humans who worked close contact with infected pigs. The case fatality rate approximately 40%. Since 2001, NiV has re-emerged Bangladesh and India where fruit bats (
Lassa virus (LASV) infects several hundred thousand people in Western Africa, resulting many lethal fever (LF) cases. Licensed LF vaccines are not available, and anti-LF therapy is limited to off-label use of the nucleoside analog ribavirin with uncertain efficacy. We describe generation a novel live-attenuated LASV vaccine candidate. This candidate based on mutating wild-type (WT) key region viral genome, glycoprotein precursor (GPC) gene. These mutations do change encoded GPC but interfere...
ABSTRACT Simian hemorrhagic fever virus (SHFV) causes a severe and almost uniformly fatal viral in Asian macaques but is thought to be nonpathogenic for humans. To date, the SHFV life cycle completely uncharacterized on molecular level. Here, we describe first steps of cycle. Our experiments indicate that enters target cells by low-pH-dependent endocytosis. Dynamin inhibitors, chlorpromazine, methyl-β-cyclodextrin, chloroquine, concanamycin A dramatically reduced entry efficiency, whereas...
Identifying effective antivirals for treating Ebola virus disease (EVD) and minimizing transmission of such is critical. A variety cell-based assays have been developed evaluating compounds activity against virus. However, very few reports discuss the variable assay conditions that can affect results obtained from these drug screens. Here, we describe tested during development our screen designed to identify with anti-Ebola using established cell lines human primary cells. The effect...
Lassa virus (LASV), a mammarenavirus, infects an estimated 100,000⁻300,000 individuals yearly in western Africa and frequently causes lethal disease. Currently, no LASV-specific antivirals or vaccines are commercially available for prevention treatment of fever, the disease caused by LASV. The development medical countermeasure screening platforms is crucial step to yield licensable products. Using reverse genetics, we generated recombinant wild-type LASV (rLASV-WT) modified version thereof...
As the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic expanded, it was clear that effective testing for presence of neutralizing antibodies in blood convalescent patients would be critical development plasma-based therapeutic approaches. To address need a high-quality neutralization assay against SARS-CoV-2, previously established fluorescence reduction (FRNA) Middle East (MERS-CoV) modified and optimized. The SARS-CoV-2 FRNA provides quantitative assessment large...
Middle East respiratory syndrome coronavirus (MERS-CoV) is a recently isolated betacoronavirus identified as the etiologic agent of frequently fatal disease in Western Asia, syndrome. Attempts to identify natural reservoirs MERS-CoV have focused part on dromedaries. Bats are also suspected be based frequent detection other betacoronaviruses these mammals. For this study, ten distinct cell lines derived from bats divergent species were exposed MERS-CoV. Plaque assays, immunofluorescence and...
Little is known about the repertoire of cellular factors involved in replication pathogenic alphaviruses. To uncover molecular regulators alphavirus infection, and to identify candidate drug targets, we performed a high-content imaging-based siRNA screen. We revealed an actin-remodeling pathway involving Rac1, PIP5K1- α, Arp3, as essential for infection by Infection causes actin rearrangements into large bundles filaments termed foci. Actin foci are generated late concomitantly with envelope...
All viruses balance interactions between cellular machinery co-opted to support replication and host factors deployed halt the infection. We use gene correlation analysis perform an unbiased screen for involved in influenza A virus (FLUAV) Our identifies factor epidermal growth receptor pathway substrate 8 (EPS8) as highest confidence pro-viral candidate. Knockout overexpression of EPS8 confirm its importance enhancing FLUAV infection titers. Loss does not affect virion attachment, uptake,...
Lassa virus (LASV), the causative agent of fever, infects several hundred thousand people in Western Africa, resulting many lethal fever cases. No U.S. Food and Drug Administration-licensed countermeasures are available to prevent or treat LASV infection. We describe generation a novel live-attenuated vaccine candidate rLASV(IGR/S-S), which is based on replacement large genomic segment noncoding intergenic region (IGR) with that small genome segment. rLASV(IGR/S-S) less fit cell culture than...
Experimental vaccines for the deadly zoonotic Nipah (NiV), Hendra (HeV), and Ebola (EBOV) viruses have focused on targeting individual viruses, although their geographical bat reservoir host overlaps warrant creation of multivalent vaccines. Here we explored whether replication-incompetent pseudotyped vesicular stomatitis virus (VSV) virions or NiV-based virus-like particles (VLPs) were suitable vaccine platforms by co-incorporating multiple surface glycoproteins from NiV, HeV, EBOV onto...
The recent identification of highly divergent influenza A viruses in bats revealed a new, geographically dispersed viral reservoir. To investigate the molecular mechanisms host-restricted tropism and potential for transmission between humans bats, we exposed panel cell lines from diverse species to prototypical human-origin virus. All tested bat were susceptible virus infection. Experimental evolution human avian-like cells resulted efficient replication created cytopathic variants. Deep...
The papilionoid legume genus Ormosia comprises approximately 130 species, which are distributed mostly in the Neotropics, with some species eastern Asia and northeastern Australia. taxonomy evolutionary history remain unclear due to lack of a robust species-level phylogeny. Chloroplast genomes can provide important information for phylogenetic population genetic studies. In this study, we determined complete chloroplast genome sequences five by Illumina sequencing. displayed typical...
The 2014–2015 Ebola virus disease (EVD) epidemic in West Africa was the largest history. three most affected countries, Guinea, Liberia and Sierra Leone, have faced enormous challenges controlling transmission providing clinical care for patients with EVD. Chinese government, response to requests of WHO governments responded rapidly by deploying military medical teams (CMMTs) areas struck deadly epidemic. A total CMMTs, comprising 115 professionals, were rotationally deployed Freetown, Leone...
The ability to appropriately mimic human disease is critical for using animal models as a tool understanding virus pathogenesis. In the case of Nipah (NiV), infection humans appears occur either through inhalation, contact with or consumption infected material. two these circumstances, respiratory sinusoidal exposure represents likely route infection. this study, intermediate-size aerosol particles (~7 μm) NiV-Malaysia were used potential routes by focusing viral deposition in upper tract....
Filoviruses, such as Ebola virus and Marburg virus, are of significant human health concern. From 2013 to 2016, caused 11,323 fatalities in Western Africa. Since 2018, two disease outbreaks the Democratic Republic Congo resulted 2354 fatalities. Although there is progress medical countermeasure (MCM) development (in particular, vaccines antibody-based therapeutics), need for efficacious small-molecule therapeutics remains unmet. Here we describe a novel high-throughput screening assay...
Sangivamycin is a nucleoside analog that well tolerated by humans and broadly active against phylogenetically distinct viruses, including arenaviruses, filoviruses, orthopoxviruses. Here, we show sangivamycin potent antiviral multiple variants of replicative severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with half-maximal inhibitory concentration in the nanomolar range several cell types. suppressed SARS-CoV-2 replication greater efficacy than remdesivir (another broad-spectrum...
Antibody titers against a viral pathogen are typically measured using an antigen binding assay, such as enzyme-linked immunosorbent assay (ELISA), which only measures the ability of antibodies to identify interest. Neutralization assays measure presence virus-neutralizing in sample. Traditional neutralization assays, plaque reduction test (PRNT), often difficult use on large scale due being both labor and resource intensive. Here we describe Ebola virus fluorescence (FRNA), tests for...
MECR-related neurologic disorder, also known as mitochondrial enoyl CoA reductase protein-associated neurodegeneration (MEPAN) or dystonia with optic atrophy and basal ganglia abnormalities in childhood (MIM: #617282), is an autosomal recessive inherited disease characterized by a progressive childhood-onset movement disorder atrophy. Here we report 19-year-old male, presented visual failure, nystagmus, right orbital pain, no history of eye his childhood. His decline started at age 18 years,...
Abstract Lassa virus (LASV) is a rodent-borne mammarenavirus that causes tens to hundreds of thousands human infections annually in Western Africa. Approximately 20% these progress fever (LF), an acute disease with case–fatality rates from ≈20–70%. Currently, there are no approved vaccines or specific therapeutics prevent treat LF. The LASV genome consists small (S) segment has two genes, GP and NP , large (L) L Z . In both segments, the genes separated by non-coding intergenic regions...
In 2012, the genome of a novel rhabdovirus, Bas-Congo virus (BASV), was discovered in acute-phase serum Congolese patient with presumed viral hemorrhagic fever. absence replicating isolate, fulfilling Koch's postulates to determine whether BASV is indeed human and/or pathogen has been impossible. However, experiments vesiculoviral particles pseudotyped glycoprotein suggested that can enter cells from multiple animals, including humans. 2015, genomes two related viruses, Ekpoma 1 (EKV-1) and...
Simian hemorrhagic fever (SHF) is an often lethal disease of Asian macaques. virus (SHFV) one at least three distinct simian arteriviruses that can cause SHF, but pathogenesis studies using modern methods have been scarce. Even seemingly straightforward studies, such as examining viral tissue and cell tropism in vivo, difficult to conduct due the absence standardized SHFV-specific reagents. Here we report establishment situ hybridization assay for detection SHFV distantly related Kibale red...
ABSTRACT The new rhabdoviral genus Tibrovirus currently has two members, Coastal Plains virus and Tibrogargan virus. Here, we report the coding-complete genome sequence of a putative member this genus, Bivens Arm A genomic comparison reveals to be closely related to, but distinct from,