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. West Nile (WNV) is an emerging virus that was introduced in the United States on 1999 and has expanded rapidly throughout the country. This virus caused more than 12,000 reported human cases in the last two years with clinical symptoms that ranged from a mild febrile illness to a potentially fatal encephalitis. Little is known about WNV transmission in dengue-endemic regions, such as Central and South America and the Caribbean islands. Epizootic studies demonstrated that the virus is circulating in horses, birds and probably humans but symptomatic WN cases have not yet been reported in these countries. Since there is extensive cross reactivity between DEN and WNV antigens, our hypothesis is that individuals that are immune to dengue viruses (DENV) may be cross-protected against WNV illnesses. To prove this hypothesis, we will perform animal studies using Balb/c mice. We will first evaluate the susceptibility and kinetics of WNV infection in this mice strain (specific aim 1). Then, two separate experiments will be performed to test if cross-protection against WNV can be achieved by active immunization with DENV or a DEN-2 DNA vaccine candidate (specific aim 2) or passive immunization with human serum collected from primary or secondary DENV infections (specific aim 3). Immune responses against DENV and WNV will be measured by indirect immunofluorescence assays, neutralization tests and cytokine assays using the Bio-plex system. Mice morbidity and mortality after WNV challenge will be monitored for 28 days and viral loads in blood and brain will be determined by Taqman assays. If cross-protection is achieved, these experiments will allow us to determine the type and duration of the immune responses that may correlate with protection. Future studies will be aimed to determine the DEN viral proteins that may play an important role in cross-protection. Results from this and future studies in monkeys will provide valuable information to improve the design of broad spectrum vaccines that could potentially protect against both pathogens, DENV and WNV.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Research Centers in Minority Institutions Award (G12)
Project #
2G12RR003051-26
Application #
8357166
Study Section
Special Emphasis Panel (ZRR1-RI-B (02))
Project Start
2011-09-15
Project End
2012-07-31
Budget Start
2011-09-15
Budget End
2012-07-31
Support Year
26
Fiscal Year
2011
Total Cost
$105,977
Indirect Cost
Name
University of Puerto Rico Med Sciences
Department
Pharmacology
Type
Schools of Medicine
DUNS #
948108063
City
San Juan
State
PR
Country
United States
Zip Code
00936
Roche-Lima, Abiel; Carrasquillo-Carrión, Kelvin; Gómez-Moreno, Ramón et al. (2018) The Presence of Genotoxic and/or Pro-inflammatory Bacterial Genes in Gut Metagenomic Databases and Their Possible Link With Inflammatory Bowel Diseases. Front Genet 9:116
Colón-Cruz, Luis; Kristofco, Lauren; Crooke-Rosado, Jonathan et al. (2018) Alterations of larval photo-dependent swimming responses (PDR): New endpoints for rapid and diagnostic screening of aquatic contamination. Ecotoxicol Environ Saf 147:670-680
Rullán-Lind, Carlos; Pietri, Ruth B; Vázquez-Cintrón, Melvin et al. (2018) Fused dimerization increases expression, solubility, and activity of bacterial dehydratase enzymes. Protein Sci 27:969-975
Martínez-Rivera, Freddyson J; Barreto-Estrada, Jennifer L (2018) Reply to: Does High-Frequency Deep Brain Stimulation in Dorsal Regions of the Ventral Striatum Impair Extinction of Morphine-Induced Place Preference? Biol Psychiatry 83:e21
Ebersole, J L; Dawson 3rd, D A; Emecen Huja, P et al. (2018) Age and Periodontal Health - Immunological View. Curr Oral Health Rep 5:229-241
Ebersole, Jeffrey L; Orraca, Luis; Kensler, Terry B et al. (2018) Periodontal disease susceptible matrilines in the Cayo Santiago Macaca mulatta macaques. J Periodontal Res :
Ramírez, Maite; Santos, Saritza; Martínez, Osmarie et al. (2018) Characterization of the immune response elicited by the vaccinia virus L3 protein delivered as naked DNA. Vaccine 36:2049-2055
Vaquer-Alicea, Ana Del C; Vázquez-Torres, Rafael; Devarie-Hornedo, Marcos et al. (2018) aPKC-Mediated Persistent Increase in AMPA/NMDA Ratio in the VTA Participates in the Neuroadaptive Signal Necessary to Induce NAc Synaptic Plasticity After Cocaine Administration. Neuroscience 392:129-140
Anderson, Julia; Seol, Haeri; Gordish-Dressman, Heather et al. (2017) Interleukin 1 Receptor-Like 1 Protein (ST2) is a Potential Biomarker for Cardiomyopathy in Duchenne Muscular Dystrophy. Pediatr Cardiol 38:1606-1612
Martínez, Osmarie; Bravo Cruz, Ariana; Santos, Saritza et al. (2017) Vaccination with a codon-optimized A27L-containing plasmid decreases virus replication and dissemination after vaccinia virus challenge. Vaccine 35:6007-6014

Showing the most recent 10 out of 414 publications