Flor
Pujol

PROJECT

Molecular evolutionary aspects of hepatitis B and D virus infection and of their co-infection in Amerindians

Amerindians are the aboriginal people in the Americas. Some viral infection are endemic in them, and quite unique, like hepatitis B and D virus Among the 240 million persons infected with HBV worldwide, 15 to 20 million are co-infected with HDV, which needs HBV co-infection. HBV/HDV co-infection leads to the most severe forms of disease, particularly in the Amazon Bassin. Up to 10 HBV genotypes (A-J) have been described. Genotype F is highly predominant in Amerindians. Eight HDV genotypes have been described. HDV genotype 3 (HDV-3) is endemic and highly prevalent in the Amazon Bassin, and is associated with outbreaks of severe fulminant hepatitis in the region. This HDV genotype is frequently found associated to the Amerindian HBV genotype F. It is not completely clear at present whereas the severe presentation of HDV/HBV co-infection is only due to the particular HDV-3. In addition to host factors, other virological factors might be influencing the severity of this disease. The aim of this project is an in deep characterization of HBV and HDV isolates from Amerindians, in terms of phylogenetic/phylodynamic analysis of the viral diversity present in the region, identification of specific signature motifs and complexity of the viral quasispecies that might be contributing to the severe clinical presentation of this disease in the region. This project is part of a collaborative project of Inserm U1052 of Lyon and the University Medical School of Salvador de Bahia. Flor Pujol will contribute in the bioinformatics HBV and HDV sequence analysis and on epidemiological review of the literature available both internationally and regionally. In addition, her stay at Lyon would allow her to interact with specialists from other domains, like Anthropologists and Human Scientists, to discuss topics on education for prevention and how some particular practices might have facilitated the introduction and dissemination of these viral diseases.

BIOGRAPHY

Flor H. Pujol performed all her studies in Venezuela: Bachelor in Biology(1982) of Universidad Simón Bolívar, Venezuela. Magister Sc. (1985) and Philosophus Sc. (1989) in Biology of Instituto Venezolano de Investigaciones Científicas (IVIC). She is at present full Professor at IVIC, Member of the Venezuelan “Academia de Ciencias Físicas, Matemáticas y Naturales” and of the Latin American Academy of Sciences. She has produced more than 140 publications. She is a regional leader on molecular epidemiology and evolution of hepatitis viruses, with unique studies on viruses infecting Amerindians from Venezuela. She was also involved in the first report of HIV-2 circulation in Venezuela, and the molecular description of a devastating epidemic of HIV-1 in Venezuela. She has also collaborated in the study of genetic diversity and molecular virology of dengue virus and gastroenteritis viruses.

BIBLIOGRAPHY

• Pujol, F.H., Favorov, M.O., Marcano, T., Esté, J.A., Magris, M., Liprandi, F., Khudyakov, Y., Khudyakova, N. y Fields, H.A. (1994): Prevalence of antibodies against hepatitis E virus among urban and rural populations in Venezuela. J. Med. Virol.42:234-236.
• Liprandi, F., Moros, Z., Gerder, M., Ludert, J.E., Pujol, F.H., Ruiz M.C., Michelangeli, F., Charpillenne, A. y Cohen, J. (1997): Productive infection of rotavirus in cultured cells induces co-entry of the translation inhibitor alpha-sarcin” Virology 237: 430-438.
• Blitz, L., Pujol, F.H., Swenson, P.D., Porto, L., Atencio, R., Araujo, M., Costa, L., Callejas-Monsalve, D., Torres, J.R., Fields, H.A., Lambert, S., Van Geyt, C., Norder, H., Magnius, L.O., Echevarría, J.M. y Stuyver, L. (1998): Antigenic diversity of hepatitis B virus strains of genotype F in Amerindians and other population groups from Venezuela. J. Clin. Microbiol. 36: 648-651.
• Quintero, A., Uzcátegui, N., Loureiro, C.L., Villegas, L., Illarramendi, X., Guevara, M., Ludert, J.E., Blitz, L., Liprandi, F. y Pujol, F.H. (2001): Hepatitis delta virus genotypes I and III circulate associated with hepatitis B virus genotype F in Venezuela. J. Med. Virol. 64: 356-359.
• Loureiro, C.L., Alonso, R., Pacheco, B.A., Uzcátegui, M.G., Villegas, L., León, G., de Saéz, A., Liprandi, F., López, J.L. y Pujol, F.H. (2002): High Prevalence of GB virus C/Hepatitis G virus genotype 3 among autochthonous Venezuelan populations. J. Med. Virol.68: 357-362.
• Torres, J.R., Torres-Viera, M.A., Schupbach, J., Rangel, H.R. y Pujol, F.H. (2007): Non-immune thrombocytopenia responsive to antiretroviral therapy and HIV-2 infection. J Infect.54: 21-24.
• Devesa, M. y Pujol, F.H. (2007): Hepatitis B virus genetic diversity in Latin America. Virus Research. 127:177-184.
• Devesa M., Loureiro C.L., Rivas Y., Monsalve-Castillo F., Cardona N., Duarte M.C., Poblete F., Gutierrez M.F., Botto C. y Pujol F.H. (2008): Subgenotype Diversity of Hepatitis B Virus American Genotype F in Amerindians from Venezuela and the General Population of Colombia. J. Med. Virol. 80:20-6.
• Pujol, F.H., Navas, M.C., Hainaut, P., Chemin, I. (2009): Worldwide genetic diversity of HBV genotypes and risk of hepatocellular carcinoma. Cancer Lett. 286: 80-88.
• Sulbarán, M.Z., Di Lello, F.A., Sulbarán, Y., Cosson, C., Loureiro, C,L., Rangel, H.R., Cantaloube, J.F., Campos, R.H., Moratorio, G., Cristina, J. y Pujol, F.H. (2010): Genetic history of Hepatitis C virus in Venezuela: high diversity and long time of evolution of HCV genotype 2. PlosONE 5: e14315.
• Rangel, H.R., Maes, M., Villalba, J., Sulbarán, Y., de Waard, J.H., Bello, G. y Pujol, F.H. (2012): Evidence of at least two introductions of HIV-1 in the Amerindian Warao population from Venezuela. PlosONE. 7:e40626.
• Villalba, J.A., Bello, G., Maes, M., Sulbaran, Y.F., Garzaro, D., Loureiro, C.L., Rangel, H.R., De Waard, J.H., Pujol, F.H. (2013): HIV-1 Epidemic in Warao Amerindians from Venezuela: Spatial phylodynamics and Epidemiological patterns. AIDS. 27:1783-1891.
• Rangel, H.R., Bello, G., Villalba, J., Sulbaran, Y.F., Garzaro, D.J., Maes, M., Loureiro, C.L., de Waard, J.H. y Pujol, F.H. (2015). The evolving HIV-1 epidemic in Warao Amerindians is dominated by an extremely high frequency of CXCR4-utilizing strains. Aids Res. Hum. Retrovir. 31: 1265-1268.
• Blanco, R.Y., Loureiro, C.L., Villalba, J.A., Sulbarán, Y.F., Maes, M., de Waard, J.H., Rangel, H.R., Jaspe, R.C., Pujol, F.H. (2018): Decreasing prevalence of Hepatitis B and absence of Hepatitis C Virus infection in the Warao indigenous population of Venezuela. PLoS One.13:e0197662.
• Parana, R. y Pujol, F.H. (2019): Clinical and virological heterogeneity of hepatitis delta in the Amazonia: more questions than answers. Clin. Liver Dis. 13: 62-65.