A5044111238- Mosquito-borne diseases and control
- Viral Infections and Vectors
- Malaria Research and Control
- Insect symbiosis and bacterial influences
- HIV Research and Treatment
- Vector-Borne Animal Diseases
- Bacterial Genetics and Biotechnology
- Computational Drug Discovery Methods
- Vector-borne infectious diseases
- Viral Infections and Outbreaks Research
- Microbial Natural Products and Biosynthesis
The University of Texas Medical Branch at Galveston
2014-2022
John Sealy Hospital
2019-2020
Galveston College
2018
Mitchell Institute
2011
The mosquito-borne disease dengue (DEN) is caused by four serologically and genetically related viruses, termed DENV-1 to DENV-4. Infection with one DENV usually leads acute illness results in lifelong homotypic immunity, but individuals remain susceptible infection the other three DENVs. lack of a small-animal model that mimics systemic DEN without neurovirulence has been an obstacle, DENV-2 models resemble human have recently developed AG129 mice (deficient interferon alpha/beta gamma...
Dengue is a mosquito-borne disease of global public health significance that caused by four serologically and genetically related viruses (DENV-1 to DENV-4). Most human DENV infections are asymptomatic, but clinical cases can range in severity from relatively mild self-limiting illness severe life-threatening disease. Infection with one serotype results life-long homotypic immunity only short term heterotypic protection. There no licensed vaccines or antivirals for dengue due part difficulty...
ABSTRACT With over 3.5 billion people at risk and approximately 390 million human infections per year, dengue virus (DENV) disease strains health care resources worldwide. Previously, we others established models for DENV pathogenesis in mice that completely lack subunits of the receptors ( Ifnar Ifngr ) type I II interferon (IFN) signaling; however, utility these is limited by pleotropic effect cytokines on innate adaptive immune system development function. Here, demonstrate specific...
Dengue is a mosquito-borne disease caused by four related but distinct dengue viruses, DENV-1 to DENV-4. endemic in most tropical countries, and over third of the world's population at risk being infected. Although global burden high, no vaccine or antiviral licensed combat this disease. An obstacle complicating research lack animal challenge models that mimic human Advances immunocompromised murine infection resulted development lethal DENV-2, DENV-3 DENV-4 AG129 mice, which are deficient...
The mosquito-borne disease dengue is caused by four serologically and genetically related flaviviruses termed DENV-1 to DENV-4. Dengue a global public health concern, with both the geographical range burden of increasing rapidly. Clinically, ranges from relatively mild self-limiting illness severe life-threatening sometimes fatal disease. Infection one DENV serotype produces life-long homotypic immunity, but incomplete short-term heterotypic protection. development small-animal models that...
Abstract The mosquito-borne disease dengue is caused by four serologically- and genetically-related viruses, termed DENV-1 to DENV-4. Historical setbacks due lack of human-like mouse models were partially remedied with characterization lethal DENV-2 infection in immunocompromised AG129 mice (deficient IFN-α/β/γ receptors). Recently, our group established DENV-1, DENV-3, DENV-4 using human isolates. Here we compare a non-lethal, disseminated model DENV-3 strain D83-144 that the outcome...
Zika virus (ZIKV) strains belong to the East African, West and Asian/American phylogenetic lineages. RNA viruses, like ZIKV, exist as populations of genetically-related sequences whose heterogeneity may impact viral fitness, evolution, virulence. Genetic diversity representative ZIKVs from each lineage was examined using next generation sequencing (NGS) paired with downstream entropy single nucleotide variant (SNV) analysis. Comparisons showed that inter-lineage statistically supported,...
The dengue virus (DENV) envelope protein domain 3 (ED3) is the target of potent neutralizing antibodies. DENV-2 ED3 contains adjacent type-specific and DENV complex-reactive antigenic sites that are composed a small number residues were previously demonstrated to be critical for antibody binding. Site-directed mutagenesis 16681 infectious clone was used mutate in (K305A P384A) (K310A) sites. K305A mutant multiplied like parent mosquito mammalian cells, as did P384A virus, which required...
Abstract Live attenuated vaccines (LAVs) are one of the most important strategies to control flavivirus diseases. The nonstructural (NS) 4B proteins a critical component both virus replication complex and evasion host innate immunity. Here we have used site-directed mutagenesis residues in highly conserved N-terminal central hydrophobic regions Zika (ZIKV) NS4B protein identify candidate attenuating mutations. Three single-site mutants were generated, which NS4B-C100S mutant was more than...
The envelope (E) protein of flaviviruses is functionally associated with viral tissue tropism and pathogenicity. For yellow fever virus (YFV), viscerotropic disease primarily involving the liver pathognomonic for wild-type (WT) infection. In contrast, live-attenuated vaccine (LAV) strain 17D does not cause reversion to virulence neurotropic disease. relationship between structure-function E WT Asibi its LAV derivative poorly understood; however, changes epitopes have been in virulence. Here,...
Zika virus (ZIKV) is a mosquito-borne Flavivirus. Previous studies have shown that mosquito-transmitted flaviviruses, including yellow fever, Japanese encephalitis, and West Nile viruses, could be attenuated by serial passaging in human HeLa cells. Therefore, it was hypothesized wild-type ZIKV would also after cell passaging. A isolate from the recent epidemic subjected to passaging, resulting vitro replication both Vero A549 Additionally, infection of AG129 mice with 10 plaque forming units...
Abstract Although live attenuated vaccines (LAVs) have been effective in the control of flavivirus infections, to date they excluded from Zika virus (ZIKV) vaccine trials due safety concerns. We previously reported two ZIKV mutants, each which has a single substitution either envelope (E) glycosylation or nonstructural (NS) 4B P36 and displays modest reduction mouse neurovirulence neuroinvasiveness, respectively. Here, we generated mutant, ZE4B-36, combines mutations both E NS4B P36. The...
The Dengue virus (DENV) envelope (E) protein is the major component of viral surface and structurally subdivided into three domains, ED1, ED2 ED3. ED3 elicits potent neutralizing antibodies contains two antigenic sites: DENV-type-specific DENV-complex-reactive sites. Each site composed a limited subset residues that are required for monoclonal antibody (mAb) binding. Here we show DENV-2-type-specific mAb 9A3D-8 utilizes functionally critical K307, V308, K310, I312, P332, L387, L389 N390...
Zika virus (ZIKV) is a mosquito-transmitted positive-sense RNA in the family Flaviviridae. Candidate live-attenuated vaccine (LAV) viruses with engineered deletions 3' untranslated region (UTR) provide immunity and protection animal models of ZIKV infection, phenotypic studies show that LAVs retain protective abilities following vitro passage. The present study investigated genetic diversity wild-type (WT) parent its candidate using next generation sequencing analysis five sequential...