Hepatitis C virus pharmacogenomics in Latin American populations: implications in the era of direct-acting antivirals

In recent years, great progress has been made in the field of new therapeutic options for hepatitis C virus (HCV) infection. The new direct-acting antiviral agents (DAAs) represent a great hope for millions of chronically infected individuals because their use may lead to excellent cure rates with fewer side effects. In Latin America, the high prevalence of HCV genotype 1 infection and the significant association of Native American ancestry with risk predictive single-nucleotide polymorphisms (SNPs) in IFNL4 and ITPA genes highlight the need to implement new treatment regimens in these populations. However, the universal accessibility to DAAs is still not a reality in the region as their high cost is one of the major, although not the only, limiting factors for their broad implementation. Therefore, under these circumstances, could the assessment of host genetic markers be a useful tool to prioritize DAA treatment until global access to these new drugs can be achieved? This review will summarize the scientific evidences and the potential implications of HCV pharmacogenomics in this rapidly evolving era of anti-HCV drug development.Fil: Trinks, Julieta. Hospital Italiano. Instituto de Ciencias Básicas y Medicina Experimental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Caputo, Mariela. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Servicio de Huellas Digitales Genéticas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Hulaniuk, María L.. Hospital Italiano. Instituto de Ciencias Básicas y Medicina Experimental; ArgentinaFil: Corach, Daniel. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Servicio de Huellas Digitales Genéticas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Flichman, Diego Martin. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Genetic diversity and phylogeographic analysis of human herpesvirus type 8 (HHV-8) in two distant regions of Argentina: Association with the genetic ancestry of the population

Background: The genetic diversity of persistent infectious agents, such as HHV-8, correlates closely with the migration of modern humans out of East Africa which makes them useful to trace human migrations. However, there is scarce data about the evolutionary history of HHV-8 particularly in multiethnic Latin American populations. Objectives: The aims of this study were to characterize the genetic diversity and the phylogeography of HHV-8 in two distant geographic regions of Argentina, and to establish potential associations with pathogenic conditions and the genetic ancestry of the population. Study design: A total of 101 HIV-1 infected subjects, 93 Kaposi´s Sarcoma (KS) patients and 411 blood donors were recruited in the metropolitan (MET) and north-western regions of Argentina (NWA). HHV-8 DNA was detected by ORF-26 PCR in whole blood, saliva and FFPE tissues. Then, ORF-26 and ORF-K1 were analyzed for subtype assignment. Mitochondrial DNA and Y chromosome haplogroups, as well as autosomal ancestry markers were evaluated in samples in which subtypes could be assigned. Phylogeographic analysis was performed in the ORF-K1 sequences from this study combined with 388 GenBank sequences. Results: HHV-8 was detected in 50.7%, 59.2% and 8% of samples from HIV-1 infected subjects, KS patients and blood donors, respectively. ORF-K1 phylogenetic analyses showed that subtypes A (A1-A5), B1, C (C1-C3) and F were present in 46.9%, 6.25%, 43.75% and 3.1% of cases, respectively. Analyses of ORF-26 fragment revealed that 81.95% of strains were subtypes A/C followed by J, B2, R, and K. The prevalence of subtype J was more commonly observed among KS patients when compared to the other groups. Among KS patients, subtype A/C was more commonly detected in MET whereas subtype J was the most frequent in NWA. Subtypes A/C was significantly associated with Native American maternal haplogroups (p = 0.004), whereas subtype J was related to non-Native American haplogroups (p < 0.0001). Sub-Saharan Africa, Europe and Latin America were the most probable locations from where HHV-8 was introduced to Argentina. Conclusions: These results give evidence of the geographic circulation of HHV-8 in Argentina, suggest the association of ORF-26 subtype J with KS development and provide new insights about its relationship with ancient and modern human migrations and identify the possible origins of this virus in Argentina.Fil: Hulaniuk Wolaniuk, Maria Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional e Ingeniería Biomédica - Hospital Italiano. Instituto de Medicina Traslacional e Ingeniería Biomédica.- Instituto Universitario Hospital Italiano de Buenos Aires. Instituto de Medicina Traslacional e Ingeniería Biomédica; Argentina. Instituto Universitario del Hospital Italiano de Buenos Aires; ArgentinaFil: Mojsiejczuk, Laura Noelia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones en Bacteriología y Virología Molecular;Fil: Jauk, Federico. Hospital Italiano; ArgentinaFil: Remondegui, Carlos. Gobierno de la Provincia de San Salvador de Jujuy. Hospital San Roque. Servicio de Infectología y Medicina Tropical; ArgentinaFil: Mammana, Lilia. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; ArgentinaFil: Bouzas, María Belén. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; ArgentinaFil: Zapiola, Inés. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; ArgentinaFil: Ferro, María Verónica. Gobierno de la Provincia de San Salvador de Jujuy. Hospital San Roque. Servicio de Infectología y Medicina Tropical; ArgentinaFil: Ajalla, Claudia. Gobierno de la Provincia de San Salvador de Jujuy. Hospital San Roque. Servicio de Infectología y Medicina Tropical; ArgentinaFil: Blejer, Jorgelina L.. Fundación Hemocentro Buenos Aires; ArgentinaFil: Alter, Adriana. Fundación Hemocentro Buenos Aires; ArgentinaFil: Acevedo, María Elina. Fundación Hemocentro Buenos Aires; ArgentinaFil: Rodríguez, Eulalia. Fundación Hemocentro Buenos Aires; ArgentinaFil: Fernández, Roberto. Fundación Hemocentro Buenos Aires; ArgentinaFil: Bartoli, Sonia. Gobierno de la Provincia de San Salvador de Jujuy. Hospital “Pablo Soria”. Servicio de Hemoterapia; ArgentinaFil: Volonteri, Victoria. Hospital Italiano; ArgentinaFil: Kohan, Dana. Centro Privado de Patología; ArgentinaFil: Elsner, Boris. Centro Privado de Patología; ArgentinaFil: Bürgesser, María Virginia. Centro de Anatomía Patológica y Citopatología; ArgentinaFil: Reynaud, Ana Laura. Laboratorio de Patología y Citopatología; ArgentinaFil: Sánchez, Marisa. Instituto Universitario del Hospital Italiano de Buenos Aires; ArgentinaFil: González, Carlos. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; ArgentinaFil: Garcia Rivello, Hernan Jorge. Instituto Universitario del Hospital Italiano de Buenos Aires; ArgentinaFil: Corach, Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Servicio de Huellas Digitales Genéticas; ArgentinaFil: Caputo, Mariela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Servicio de Huellas Digitales Genéticas; ArgentinaFil: Trinks, Julieta. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional e Ingeniería Biomédica - Hospital Italiano. Instituto de Medicina Traslacional e Ingeniería Biomédica.- Instituto Universitario Hospital Italiano de Buenos Aires. Instituto de Medicina Traslacional e Ingeniería Biomédica; Argentin