A5063479878- interferon and immune responses
- SARS-CoV-2 and COVID-19 Research
- Viral Infections and Vectors
- Viral Infections and Outbreaks Research
- Mosquito-borne diseases and control
- COVID-19 Clinical Research Studies
- Viral gastroenteritis research and epidemiology
- Insect Utilization and Effects
- Microbial Metabolism and Applications
- Virology and Viral Diseases
- Virus-based gene therapy research
- Animal Virus Infections Studies
- Insect symbiosis and bacterial influences
- Influenza Virus Research Studies
- SARS-CoV-2 detection and testing
- Ubiquitin and proteasome pathways
- Cytokine Signaling Pathways and Interactions
- Insect behavior and control techniques
- COVID-19 epidemiological studies
- Hepatitis B Virus Studies
- Immune responses and vaccinations
- Bacteriophages and microbial interactions
- Enzyme Production and Characterization
- Immune Response and Inflammation
- Invertebrate Immune Response Mechanisms
National Institute of Allergy and Infectious Diseases
2023-2025
National Institutes of Health
2023-2025
The University of Texas Medical Branch at Galveston
2017-2024
Johns Hopkins University
2016-2018
Iowa State University
2017
The genome of SARS-CoV-2 encodes two viral proteases (NSP3/papain-like protease and NSP5/3C-like protease) that are responsible for cleaving polyproteins during replication. Here, we discovered new functions the NSP3 NSP5 SARS-CoV-2, demonstrating they could directly cleave proteins involved in host innate immune response. We identified 3 were specifically selectively cleaved by or NSP5: IRF-3, NLRP12 TAB1, respectively. Direct cleavage IRF3 explain blunted Type-I IFN response seen...
Type I interferons (IFN-I) are essential to establish antiviral innate immunity. Unanchored (or free) polyubiquitin (poly-Ub) has been shown regulate IFN-I responses. However, few unanchored poly-Ub interactors known. To identify factors regulated by in a physiological setting, we developed an approach isolate from lung tissue. We identified the RNA helicase DHX16 as potential pattern recognition receptor (PRR). Silencing of cells and vivo diminished responses against influenza virus. These...
Ebolavirus (EBOV) belongs to a family of highly pathogenic viruses that cause severe hemorrhagic fever in humans. EBOV replication requires the activity viral polymerase complex, which includes cofactor and Interferon antagonist VP35. We previously showed covalent ubiquitination VP35 promotes virus by regulating interactions with complex. In addition, can also interact non-covalently ubiquitin (Ub); however, function this interaction is unknown. Here, we report interacts free (unanchored)...
Abstract The emergence of the Omicron lineage represented a major genetic drift in SARS-CoV-2 evolution. This was associated with phenotypic changes including evasion pre-existing immunity and decreased disease severity. Continuous evolution within raised concerns potential increased transmissibility and/or To address this, we evaluate fitness pathogenesis contemporary variants XBB.1.5, XBB.1.16, EG.5.1, JN.1 upper (URT) lower respiratory tract (LRT). We compare vivo infection Syrian...
Abstract Ebola virus (EBOV) and Marburg (MARV) are zoonotic filoviruses that cause hemorrhagic fever in humans. Correlative data implicate bats as natural EBOV hosts, but neither a full-length genome nor an isolate has been found any sampled. Here, we model filovirus infection the Jamaican fruit bat (JFB), Artibeus jamaicensis, by inoculation with either or MARV through combination of oral, intranasal, subcutaneous routes. Infection results systemic replication oral shedding infectious...
WNV is a mosquito-borne flavivirus that poses threat to human health across large discontinuous areas throughout the world. Infection with results in febrile illness, which can progress severe neurological disease. Currently, there are no approved treatment options control infection. Understanding cellular immune responses regulate viral replication important diversifying resources available WNV. Here, we show elimination of TRIM6 cells an increase and alters expression function other...
Abstract The most recent Sudan virus (SUDV) outbreak in Uganda was first detected September 2022 and resulted 164 laboratory-confirmed cases 77 deaths. There are no approved vaccines against SUDV. Here, we investigated the protective efficacy of ChAdOx1-biEBOV cynomolgus macaques using a prime or prime-boost regimen. is replication-deficient simian adenovirus vector encoding SUDV Ebola (EBOV) glycoproteins (GPs). Intramuscular vaccination induced EBOV GP-specific immunoglobulin G responses...
Abstract Mosquito larvae continuously encounter microbes in their aquatic environment, which serve as food and play a critical role successful development. In previous work, we isolated Chromobacterium sp. ( C .sp_P) with larvicidal activity from the midgut of dengue vector Aedes mosquitoes Panama. this study, found positive correlation between initial concentrations .sp_P larval mortality rates, that is more efficient at inducing high nutrient environment. Multiple species induce similar...
Ebola virus (EBOV) VP35 is a polyfunctional protein involved in viral genome packaging, polymerase function, and host immune antagonism. The mechanisms regulating VP35’s engagement different functions are not well-understood. We previously showed that the E3 ubiquitin ligase TRIM6 ubiquitinates at lysine 309 (K309) to facilitate replication. However, how K309 ubiquitination regulates function of as co-factor precise stage(s) EBOV replication cycle require known. Here, we generated...
SARS-CoV-2 is a highly transmissible virus that causes COVID-19 disease. Mechanisms of viral pathogenesis include excessive inflammation and viral-induced cell death, resulting in tissue damage. We identified the host E3-ubiquitin ligase TRIM7 as an inhibitor apoptosis replication via ubiquitination membrane (M) protein.
Genetic diversity of porcine reproductive and respiratory syndrome virus (PRRSV) challenges efforts to develop effective broadly acting vaccines. Although genetic variation in PRRSV has been extensively documented, the effects this on phenotype are less well understood. In present study, open reading frame (ORF)2–6 variants predominant during first six weeks following experimental infection were characterized for antigenic replication phenotype. There was limited these early times after...
Vector control is critical in reducing the disease burden caused by mosquitoes, and insecticides are an effective tool to vector populations. Resistance common now widespread, novel classes of needed. In previous work, we described mosquitocidal activity Chromobacterium sp. Panama (C.sp_P), a bacterium found association with mosquitoes natural current further explored effects exposure on mosquito fitness physiology. We that C.sp_P has against broad range taxa. When exposed as adults, female...
The emergence of the Omicron lineage represented a major genetic drift in SARS-CoV-2 evolution. This was associated with phenotypic changes including evasion pre-existing immunity and decreased disease severity. Continuous evolution within raised concerns potential increased transmissibility and/or To address this, we evaluated fitness pathogenesis contemporary variants XBB.1.5, XBB.1.16, EG.5.1, JN.1 upper (URT) lower respiratory tract (LRT). We compared vivo infection Syrian hamsters...
Abstract The genome of SARS-CoV-2 (SARS2) encodes for two viral proteases (NSP3/ papain-like protease and NSP5/ 3C-like or major protease) that are responsible cleaving polyproteins successful replication. NSP3 NSP5 SARS-CoV (SARS1) known interferon antagonists. Here, we examined whether the function SARS2 target proteins involved in host innate immune response. We designed a fluorescent based cleavage assay to rapidly screen activity on library 71 human (HIIPs), covering most pathways...
Abstract The ancestral sarbecovirus giving rise to SARS-CoV-2 is posited have originated in bats. While causes asymptomatic severe respiratory disease humans, little known about the biology, virus tropism, and immunity of SARS-CoV-2-like sarbecoviruses has been shown infect multiple mammalian species, including various rodent non-human primates, Egyptian fruit We show that can utilize Jamaican bat ( Artibeus jamaicensis) ACE2 spike for entry vitro. Therefore, we investigate as a possible...
Summary Ebola virus (EBOV) and Marburg (MARV) are zoonotic filoviruses that cause hemorrhagic fever in humans. Bat species both Chiropteran suborders host filoviruses, suggesting bats may have coevolved with this viral family. Correlative data implicate as natural EBOV hosts, but neither a full-length genome nor an isolate has been found any sampled. Here, we modelled filovirus infection the Jamaican fruit bat (JFB), Artibeus jamaicensis . Bats were inoculated either or MARV through...
Abstract Ebolavirus (EBOV) belongs to a family of highly pathogenic viruses that cause severe hemorrhagic fever in humans. EBOV replication requires the activity viral polymerase complex, which includes co-factor and Interferon antagonist VP35. We previously showed covalent ubiquitination VP35 promotes virus by regulating interactions with complex. In addition, can also interact non-covalently ubiquitin (Ub); however, function this interaction is unknown. Here, we report interacts free...
Nipah virus (NiV; genus: Henipavirus; family: Paramyxoviridae) naturally infects Old World fruit bats (family Pteropodidae) without causing overt disease. Conversely, NiV infection in humans and other mammals can be lethal. Comparing bat antiviral responses with those of may illuminate the mechanisms that facilitate bats’ tolerance. Tripartite motif proteins (TRIMs), a large family E3-ubiquitin ligases, fine-tune innate immune responses, two human TRIMs interact Henipavirus proteins. We...
Abstract The most recent Sudan virus (SUDV) outbreak in Uganda was first detected September 2022 and resulted 164 laboratory-confirmed cases 77 deaths. Currently, there are no approved vaccines or therapeutics against SUDV. In the current study, we investigated protective efficacy of ChAdOx1-biEBOV cynomolgus macaques using a prime prime-boost regimen. is replication-deficient simian adenovirus vector encoding SUDV Ebola (EBOV) glycoproteins (GPs) at E1 E4 loci, respectively. Intramuscular...
Abstract The ancestral sarbecovirus giving rise to SARS-CoV-2 is posited have originated in bats. While causes asymptomatic severe respiratory disease humans, little known about the biology, virus tropism, and immunity of SARS-CoV-2-like sarbecoviruses has been shown infect multiple mammalian species, including various rodent non-human primates, Egyptian fruit Here, we investigate Jamaican bat ( Artibeus jamaicensis) as a possible model species study reservoir responses. can utilize ACE2...