- Mosquito-borne diseases and control
- Malaria Research and Control
- Viral Infections and Vectors
- Viral gastroenteritis research and epidemiology
- Viral Infections and Immunology Research
- HIV Research and Treatment
- Bacteriophages and microbial interactions
- Insect symbiosis and bacterial influences
- Insect Pest Control Strategies
- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- Virology and Viral Diseases
- interferon and immune responses
- Viral Infections and Outbreaks Research
- Animal Disease Management and Epidemiology
- SARS-CoV-2 and COVID-19 Research
- SARS-CoV-2 detection and testing
- Dengue and Mosquito Control Research
- RNA regulation and disease
- Insect-Plant Interactions and Control
- Insect Resistance and Genetics
- Biosensors and Analytical Detection
- Respiratory viral infections research
- Vector-borne infectious diseases
- Pancreatic and Hepatic Oncology Research
Colorado State University
2016-2025
Clinical Research Solutions
2023
University of California, San Francisco
2016-2021
UCSF Helen Diller Family Comprehensive Cancer Center
2016-2021
Purdue University West Lafayette
2006-2016
University of California, Irvine
2004-2007
State Street (United States)
2006
Instituto Venezolano de Investigaciones Científicas
2004
Dengue virus (DENV) modifies cellular membranes to establish its sites of replication. Although the 3D architecture these structures has recently been described, little is known about pathways required for their formation and expansion. In this report, we examine host requirements DENV replication using a focused RNAi analysis combined with validation studies pharmacological inhibitors. This approach identified three replication: autophagy, actin polymerization, fatty acid biosynthesis....
Abstract Ticks transmit more pathogens to humans and animals than any other arthropod. We describe the 2.1 Gbp nuclear genome of tick, Ixodes scapularis (Say), which vectors that cause Lyme disease, human granulocytic anaplasmosis, babesiosis diseases. The large reflects accumulation repetitive DNA, new lineages retro-transposons, gene architecture patterns resembling ancient metazoans rather pancrustaceans. Annotation scaffolds representing ∼57% genome, reveals 20,486 protein-coding genes...
Dengue virus causes ∼50–100 million infections per year and thus is considered one of the most aggressive arthropod-borne human pathogen worldwide. During its replication, dengue induces dramatic alterations in intracellular membranes infected cells. This phenomenon observed both vector-derived Using high-resolution mass spectrometry mosquito cells, we show that this membrane remodeling directly linked to a unique lipid repertoire induced by infection. Specifically, 15% metabolites detected...
In 2015, Zika virus (ZIKV; Flaviviridae; Flavivirus) emerged in the Americas, causing millions of infections dozens countries. The rapid spread and association with disease outcomes such as Guillain-Barré syndrome microcephaly make understanding transmission dynamics essential. Currently, there are no reports vector competence (VC) American mosquitoes for ZIKV isolates from Americas. Further, it is not clear whether strains other genetic lineages can be transmitted by Aedes aegypti...
The structure of a virus linked to neurological disease reveals how drugs targeting viruses in this family can be modified.
During dengue virus infection of host cells, intracellular membranes are rearranged into distinct subcellular structures such as double-membrane vesicles, convoluted membranes, and tubular structures. Recent electron tomographic studies have provided a detailed three-dimensional architecture the representing sites replication, but temporal spatial evidence linking membrane morphogenesis with viral RNA synthesis is lacking. Integrating techniques in tomography molecular virology, we defined...
ABSTRACT During dengue virus replication, an incomplete cleavage of the envelope glycoprotein prM, generates a mixture mature (prM-less) and prM-containing, immature extracellular particles. In this study, sequential immunoprecipitation cryoelectron microscopy revealed third type particles, partially as major prM-containing particles in serotype 2 virus. Changes proportion viral pr-M junction mutants exhibiting altered levels prM suggest that may represent intermediate subpopulation...
Dengue virus (DENV), an emerging mosquito-transmitted pathogen capable of causing severe disease in humans, interacts with host cell factors to create a more favorable environment for replication. However, few interactions between DENV and human proteins have been reported date. To identify DENV-human protein interactions, we used high-throughput yeast two-hybrid assays screen the 10 against liver activation domain library. From 45 DNA-binding clones containing either full-length viral genes...
ABSTRACT During picornavirus infection, several cellular proteins are cleaved by virus-encoded proteinases. Such cleavage events likely to be involved in the changing dynamics during intracellular viral life cycle, from translation host shutoff RNA replication virion assembly. For example, it has been proposed that there is an active switch poliovirus mediated changes RNA-binding protein affinities. This could a mechanism for controlling template selection and negative-strand synthesis, two...
We describe the first comprehensive analysis of midgut metabolome Aedes aegypti, primary mosquito vector for arboviruses such as dengue, Zika, chikungunya and yellow fever viruses. Transmission these viruses depends on their ability to infect, replicate disseminate from several tissues in vector. The metabolic environments within play crucial roles processes. Since are enveloped, viral replication, assembly release occur cellular membranes primed through manipulation host metabolism....
A rapid, specific, sensitive, and inexpensive method has been developed that detects RNA from a Zika virus strain associated with the current outbreak.
The transcriptional induction of interferon (IFN) genes is a key feature the mammalian antiviral response that limits viral replication and dissemination. A hallmark severe COVID-19 disease caused by SARS-CoV-2 low presence IFN proteins in patient serum despite elevated levels IFN-encoding mRNAs, indicative post-transcriptional inhibition protein production. Here, we performed single-molecule RNA visualization to examine expression localization host mRNAs during infection. Our data show...
G3BP1 is an RNA binding protein that condenses untranslating messenger RNAs into stress granules (SGs). inactivated by multiple viruses and thought to antagonize viral replication SG-enhanced antiviral signaling. Here, we show neither nor SGs generally alter the activation of innate immune pathways. Instead, encoded West Nile virus, Zika severe acute respiratory syndrome coronavirus 2 are prone G3BP1-dependent condensation, which enhanced limiting translation initiation correlates with...
Human enterovirus 71 is a picornavirus causing hand, foot, and mouth disease that may progress to fatal encephalitis in infants small children. As of now, no cure available for infections. Small molecule inhibitors binding into hydrophobic pocket within capsid viral protein 1 were previously shown effectively limit infectivity many picornaviruses. Here we report 3.2-Å-resolution X-ray structure the virion complexed with capsid-binding inhibitor WIN 51711. The replaced natural factor without...
Significance Enterovirus 71 (EV71) causes yearly outbreaks of hand, foot, and mouth disease in Southeast Asian countries including China Malaysia. Some the infected children develop encephalitis that can be fatal or result permanent brain damage. There are no anti-EV71 therapeutic agents available. Here it is shown an antibody had been generated by using immature EV71 virus as antigen induced release genome from virions, rendering noninfectious. The induction a mechanism which antibodies...
Background Epidemic dengue fever (DF) and hemorrhagic fever/dengue shock syndrome (DHF/DSS) are overwhelming public health capacity for diagnosis clinical care of patients throughout the tropical subtropical world. The ability to predict severe disease outcomes using acute phase specimens would be enormous value physicians workers appropriate triaging management. Advances in field metabolomics analytic software provide new opportunities identify host small molecule biomarkers (SMBs) that...
Human dengue viruses emerged from primate reservoirs, yet paradoxically does not reach high titers in models. This presents a unique opportunity to examine the genetics of spillover versus reservoir hosts. The virus 2 (DENV2) - encoded protease cleaves human STING, reducing type I interferon production and boosting viral humans. We find that both sylvatic (reservoir) universally cleave but STING primates implicated as species. special ability is thus specific humans few closely related ape...
Abstract Competition between viruses and Wolbachia for host lipids is a proposed mechanism of -mediated virus blocking in insects. Yet, the metabolomic interaction symbiont within mosquito has not been clearly defined. We compare lipid profiles Aedes aegypti mosquitoes bearing mono- or dual-infections w Mel strain dengue serotype 3 (DENV3). found metabolic signatures infection-induced intracellular events but little evidence to support direct competition lipids. Lipid dual-infected resemble...
The emergence of novel diseases spread by the Aedes aegypti mosquito in Jamaica and Caribbean, has prompted studies on insecticide resistance towards effective management vector. Though been using organophosphate malathion its vector control program for more than 30 years, to pesticide not tested over a decade. We analyzed pyrethroid insecticide, permethrin mosquitoes collected across St. Andrew, Jamaica, molecular basis resistance. Center Disease Control (CDC) bioassay revealed that Ae....
The antiviral endoribonuclease, RNase L, is activated by the mammalian innate immune response to destroy host and viral RNA ultimately reduce gene expression. Herein, we show that L L-mediated mRNA decay are primarily localized cytoplasm. Consequently, RNA-binding proteins (RBPs) translocate from cytoplasm nucleus upon activation due presence of intact nuclear RNA. re-localization RBPs coincides with global alterations processing in nucleus. While affecting many mRNAs, these pronounced mRNAs...