Analysis of inter and intra-host genetic variability of dengue virus serotype 2 (DENV2) from patients presenting dengue fever and dengue hemorrhagic fever

• Grant number: 10/12313-5
• Support Opportunities: Regular Research Grants
• Start date: November 01, 2010
• End date: October 31, 2012
• Field of knowledge: Biological Sciences - Microbiology
• Principal Investigator: Camila Malta Romano
• Grantee: Camila Malta Romano
• Host Institution: Instituto de Medicina Tropical de São Paulo (IMT). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Claudio Sergio Pannuti ; Esper Georges Kallás ; José Eduardo Levi

Abstract

About 50 to 100 million people are infected with dengue virus annually in tropical and sub-tropical regions, and it currently represents a major public health problem worldwide. Dengue is presented in distinct clinical forms, ranging from the mild to severe form. Clinical manifestation in the infected individual depends on some factors, such as the exacerbated response to a secondary infection by a distinct serotype. However, there are several reports of severe manifestations in patients experiencing primary infection, suggesting that other factors than secondary infection may influence the clinical manifestations of dengue. Among these factors, the genetic variability of viruses is often quoted. However, studies usually compare few genes in samples from distinct geographic regions and seasons, allowing other factors can interfere with the results. The possibility of verifying the complete genome of virus, sampled from 30 patients with different manifestations, and during the same epidemic, may contribute to understanding the real role of viruse's genetic variations in different manifestations of the disease. To investigate the viral genomes obtained from patients with mild and severe forms, we will sequence 30 viral full lenght genomes obtained from 15 patients presenting hemorrhagic dengue, and 15 presenting dengue fever. Still, to assess whether viral intra-host genetic variability contributes to the different clinical manifestations, we will sequence 40 clones of the envelope gene of the same 30 patients included in this project. We believe that this study not only contributes to the elucidation of immunopathogenic mechanisms of infection, as well as can be a powerful tool in vaccine development. Finally, greater knowledge in this area reveals peculiar genetic mechanisms that will increase our knowledge of genomic and viral evolution in general. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

ROMANO, CAMILA MALTA; LAUCK, MICHAEL; SALVADOR, FELIPE S.; LIMA, CELIA RODRIGUES; VILLAS-BOAS, LUCY S.; ARAUJO, EVALDO STANISLAU A.; LEVI, JOSE EDUARDO; PANNUTI, CLAUDIO SERGIO; O'CONNOR, DAVID; KALLAS, ESPER GEORGES. Inter- and Intra-Host Viral Diversity in a Large Seasonal DENV2 Outbreak. PLoS One, v. 8, n. 8, AUG 2 2013. (10/12313-5)

FELIX, ALVINA CLARA; ROMANO, CAMILA MALTA; CENTRONE, CRISTIANE DE CAMPOS; RODRIGUES, CELIA LIMA; VILLAS-BOAS, LUCY; ARAUJO, EVALDO STANISLAU; DE MATOS, ANDREIA MANSO; CARVALHO, KARINA INACIO; TURCHI MARTELLI, CELINA MARIA; KALLAS, ESPER GEORGES; et al. Low Sensitivity of NS1 Protein Tests Evidenced during a Dengue Type 2 Virus Outbreak in Santos, Brazil, in 2010. Clinical and Vaccine Immunology, v. 19, n. 12, p. 1972-1976, DEC 2012. (10/12313-5)