Identification of hepatitis C virus subtype 2c by sequencing analysis in patients from Córdoba, Argentina

Abstract

In Argentina, most information on hepatitis C virus (HCV) Hepatitis C virus (HCV) is a major worldwide agent for chronic hepatitis. Based on the nucleotide sequence divergence it is classified into six genotypes and many subtypes (Simmonds et al. 1993). The distribution of HCV genotypes and subtypes are markedly heterogeneous throughout the world, even among nearby geographical regions. The determination of HCV genotypes, subtypes and isolates has been helpful in understanding the evolution and the epidemiology of the virus. Presently, HCV genotyping constitutes the basis for the clinical management of infected patients by providing decisive information about the duration of treatment. Patients infected with HCV genotypes 1 and 4 are likely to achieve the best rate of sustained remission following a 48-week course of treatment with pegylated interferon and ribavirin, while a 24-week course of therapy appears to be sufficient to achieve the maximal rate of responsiveness in patients infected with HCV genotypes 2 and 3 (Hadziyannis et al. 2004). To perform effective public-health surveillance for new variants, modes of transmission, and further vaccine development efforts, detailed information about sequence variation of subtypes is needed (Simmonds et al. 2005, Weck 2005.Studies in Argentina from the east province (Buenos Aires region) have demonstrated that genotype 1 (principally 1b) is the most prevalent, followed by genotypes 2 and 3, and in minor extent by 4 and 5 (Oubina et al. 1995, Quarleri et al. 1998, 2000, Picchio et al. 2006). On the other hand, in a study with HCV infected patients resident in Córdoba, the second most populated province of central region of Argentina, we have found an intriguingly high percentage (55%) of genotype 2 isolates, followed by genotypes 1 (38%) and 3 (5%) (Ré et al. 2003), indicating that regional differences of genotype distribution could be present between east and central Argentina. However, no information of HCV subtype distribution in central region of Argentina is available at the present time. The main genotype was determined by restriction fragment length polymorphism analysis of 5'NCR region and polymerase chain reaction (PCR) assay using type specific primers. Although such methods are able to identify correctly the major genotypic groups, only nucleotide sequencing followed by phylogenetic analysis of protein-coding regions, such as core, envelope (E1) or non-structural (NS5) gene of HCV genome is efficient in discriminating among subtypes, since sequence variation from the 5' NCR region does not contain sufficient information to resolve subtypes (Simmonds et al. 1993, Hraber et al. 2006. In the present study, nucleotide sequencing and phylogenetic analysis of core region was performed to provide more accurate determination of HCV subtypes circulating in central Argentina.A total of 36 HCV-RNA positive sera for 5'NCR region by reverse transcription (RT)-nested PCR were sequenced. These samples (16 male, 20 female; mean age 48.2 years-old, range 21-71 years) w...

Risk Factors for Infection with Different Hepatitis C Virus Genotypes in Southern Brazil

“…Genotypes 2 (12.7%; 2a = 2.9 and 2b = 9.8) and 3 (6.2%) were less common, and genotypes 4 and 6 were also detected (1.1% and 1.8%, resp.). In Latin America countries such as Argentina and Venezuela, genotypes 1 and 2 account for almost 90% of cases [13–15]. …”

“…In studies from Spain there is a predominance of genotypes 1a and 1b [7, 8] while in other European regions genotype 2 is usually the most prevalent [4, 9–11]. Genotype 1 predominates in Central America [12], and in Latin-American countries such as Argentina [13, 14] and Venezuela [15] genotypes 1 and 2 account for 90% of cases. In Brazil, genotypes 1 and 3 are the most frequent [16, 17], but in Da Silva et al study [18] almost half of the hepatitis C patients from South of Brazil were infected by genotypes 2 and 3.…”

Phylodynamics of Hepatitis C Virus Subtype 2c in the Province of Córdoba, Argentina

“…However, in some countries, such as Italy, HCV-2c is an epidemiological important subtype, being the second most prevalent (after HCV-1b) with the particularity that it forms an increasing north-to-south gradient of prevalence and it is associated with elder patients [9]. In Cruz del Eje city, HCV-2c accounts for 90% of HCV infections, whereas in other cities and towns of the Province of Córdoba it accounts for 50% [11], [12]. The fact that 21 out of the 49 sequenced samples from Cruz del Eje belong to patients older than 70 years, as that observed in Italy, suggests that the spread of HCV in the population was a past event.…”

“…In Córdoba City (which is located in the Central region and is the Capital of the Province and the second most populated city of Argentina) and its surrounding locations, 50% of the patients carrying HCV are infected with HCV-2a/c [11]. Since the RFLP assay is carried out in a highly conserved region of the HCV genome, Ré et al [12] used additional sequence information (Core region) in a sub-sample of these patients and found that they were infected with HCV-2c.…”

Spreading of hepatitis C virus subtypes 1a and 1b through the central region of Argentina

“…Some genotypes have an endemic distribution, such as genotypes 5 and 6 (prevalent in Southern Africa and Asia respectively), whereas others have a worldwide distribution like genotypes 1, 2 and 3 (particularly subtypes 1a, 1b, 2a and 3a) (Simmonds, 2004). In Argentina, the circulation of subtypes 1a, 1b, 2c, 3a and 4a was reported (Ré et al, 2007;Kershenobich et al, 2011;del Pino et al, 2013). Although each study had yielded a different estimation of the Argentinean HCV prevalence, between 0.32% and about 2%, all agree in that the genotype 1 account for more than the half of the cases.…”