Abstract

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Considerable effort has been made to develop drugs against mosquito-borne flaviviruses, such as dengue virus (DENV), West Nile virus (WNV) and Japanese encephalitis virus (JEV). However, to date no such antiviral drugs are available. Growing evidence suggests that a particular area of the so-called stem region of the outer coating, or envelope protein, of these viruses is involved in virus entry and virus assembly. The stem contains several highly conserved amino acids among different flaviviruses. We conjecture that these highly conserved amino acids play important roles in virus entry and virus assembly. The objective of this study is to analyze the stem region of DENV and other medically important flaviviruses for novel targets that would lead to the development of antiviral drugs.
In Aim 1, we will investigate the role of the highly conserved amino acids on the entry and assembly of DENV serotype 4.
In Aim 2, we will investigate the mechanisms of impairment on the entry and assembly of DENV serotype 4. And in Aim 3, we will investigate the role of the highly conserved amino acids on the entry and assembly of other DENV serotypes, as well as WNV and JEV. Characterization of the roles of the highly conserved amino acids on virus assembly and entry would lead to new insights about the molecular mechanisms of flavivirus replication. In turn, this new knowledge will lead to the development of new antiviral drugs to reduce the human suffering and deaths associated with diseases caused by DENV and other flaviviruses.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Exploratory Grants (P20)
Project #
5P20RR018727-07
Application #
8360753
Study Section
Special Emphasis Panel (ZRR1-CR-B (01))
Project Start
2011-07-01
Project End
2012-06-30
Budget Start
2011-07-01
Budget End
2012-06-30
Support Year
7
Fiscal Year
2011
Total Cost
$221,984
Indirect Cost

  Institution

Name
University of Hawaii
Department
Pediatrics
Type
Schools of Medicine
DUNS #
965088057
City
Honolulu
State
HI
Country
United States
Zip Code
96822

  Publications

Thongsripong, Panpim; Chandler, James Angus; Green, Amy B et al. (2018) Mosquito vector-associated microbiota: Metabarcoding bacteria and eukaryotic symbionts across habitat types in Thailand endemic for dengue and other arthropod-borne diseases. Ecol Evol 8:1352-1368
Martin, Estelle; Chirivella, Maritza; Co, Juliene K G et al. (2016) Insights into the molecular evolution of Dengue virus type 4 in Puerto Rico over two decades of emergence. Virus Res 213:23-31
Roe, Kelsey; Orillo, Beverly; Verma, Saguna (2014) West Nile virus-induced cell adhesion molecules on human brain microvascular endothelial cells regulate leukocyte adhesion and modulate permeability of the in vitro blood-brain barrier model. PLoS One 9:e102598
Anderson, Cynthia D; Urschitz, Johann; Khemmani, Mark et al. (2013) Ultrasound directs a transposase system for durable hepatic gene delivery in mice. Ultrasound Med Biol 39:2351-61
Darrow, April L; Maresh, J Gregory; Shohet, Ralph V (2013) Mouse models and techniques for the isolation of the diabetic endothelium. ISRN Endocrinol 2013:165397
Thongsripong, Panpim; Green, Amy; Kittayapong, Pattamaporn et al. (2013) Mosquito vector diversity across habitats in central Thailand endemic for dengue and other arthropod-borne diseases. PLoS Negl Trop Dis 7:e2507
Sana, Theodore R; Gordon, D Benjamin; Fischer, Steven M et al. (2013) Global mass spectrometry based metabolomics profiling of erythrocytes infected with Plasmodium falciparum. PLoS One 8:e60840
Arai, Satoru; Gu, Se Hun; Baek, Luck Ju et al. (2012) Divergent ancestral lineages of newfound hantaviruses harbored by phylogenetically related crocidurine shrew species in Korea. Virology 424:99-105
Allicock, Orchid M; Lemey, Philippe; Tatem, Andrew J et al. (2012) Phylogeography and population dynamics of dengue viruses in the Americas. Mol Biol Evol 29:1533-43
Hernandez, Brenda Y; Ton, Thien; Shvetsov, Yurii B et al. (2012) Human papillomavirus (HPV) L1 and L1-L2 virus-like particle-based multiplex assays for measurement of HPV virion antibodies. Clin Vaccine Immunol 19:1348-52

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