Many studies have documented the molecular epidemiological scenario of HCV within individual Brazilian states, but we still have an incomplete understanding of the dispersion dynamics of the virus in different regions throughout the country.
Methods
A total of 676 HCV NS5B gene sequences of subtypes 1a (n=321), 1b (n=170) and 3a (n=185), isolated from seven different Brazilian states covering four out of five regions were analysed in the present study. We also analysed 22 HCV NS5B gene sequences of minor genetic variants including genotype 2 (n=13), genotype 4 (n=6) and subtype 5a (n=3). Brazilian HCV sequences were aligned with sequences of non-Brazilian origin and subjected to maximum likelihood phylogenetic analyses.
Results
These analyses revealed that the Brazilian HCV epidemic resulted from multiple introductions and autochthonous transmission of subtypes 1a, 1b, 3a and genotypes 2, 4 and 5. Brazilian HCV subtype 1a epidemic is dominated by the dissemination of one major clade; while Brazilian HCV subtypes 1b and 3a epidemics are characterized by concurrent dissemination of several independent HCV lineages. Some HCV Brazilian lineages of subtypes 1a, 1b, 2b and 3a were successful in becoming established and disseminated through several regions in the country. Despite significant phylogenetic intermixing of Brazilian sequences, the distribution of HCV strains from different states across lineages was not completely homogeneous.
Conclusions
These results demonstrate the existence of multiple introductions and local propagation of both prevalent and uncommon HCV genetic variants in Brazil and identify some major Brazilian HCV clades with nationwide dissemination. This study also suggests that the observed HCV diversity in Brazil has been shaped by both frequent viral migration among regions and in situ viral dissemination.
References
1.
LavanchyD.Evolving epidemiology of hepatitis C virus. Clin Microbiol Infect2011; 17: 107–115.
2.
SimmondsP., BukhJ., CombetC.Consensus proposals for a unified system of nomenclature of hepatitis C virus genotypes. Hepatology2005; 42: 962–973.
3.
PickettB.E., StrikerR., LefkowitzE.J.Evidence for separation of HCV subtype 1a into two distinct clades. J Viral Hepat2011; 18: 608–618.
4.
HauriA.M., ArmstrongG.L., HutinY.J.The global burden of disease attributable to contaminated injections given in health care settings. Int J STD AIDS2004; 15: 7–16.
5.
TanakaY., HanadaK., OritoE.Molecular evolutionary analyses implicate injection treatment for schistosomiasis in the initial hepatitis C epidemics in Japan. J Hepatol2005; 42: 47–53.
6.
PybusO.G., CochraneA., HolmesE.C., SimmondsP.The hepatitis C virus epidemic among injecting drug users. Infect Genet Evol2005; 5: 131–139.
ZarifeM.A., SilvaL.K., SilvaM.B.Prevalence of hepatitis C virus infection in north-eastern Brazil: a population-based study. Trans R Soc Trop Med Hyg2006; 100: 663–668.
9.
StuyverL., RossauR., WyseurA.Typing of hepatitis C virus isolates and characterization of new subtypes using a line probe assay. J Gen Virol1993; 74: 1093–1102.
10.
HollandP.V., BarreraJ.M., ErcillaM.G.Genotyping hepatitis C virus isolates from Spain, Brazil, China, and Macau by a simplified PCR method. J Clin Microbiol1996; 34: 2372–2378.
11.
MartinsR.M., VanderborghtB.O., YoshidaC.F.Hepatitis C virus genotypes among blood donors from different regions of Brazil. Mem Inst Oswaldo Cruz1998; 93: 299–300.
12.
OliveiraM.L., BastosF.I., SabinoR.R.Distribution of HCV genotypes among different exposure categories in Brazil. Braz J Med Biol Res1999; 32: 279–282.
13.
SilvaL.K., ParanaR., SouzaS.P.Hepatitis C virus genotypes in a northeastern area of Brazil. Am J Trop Med Hyg2000; 62: 257–260.
14.
PereiraL.M., SpinelliV., XimenesR.A.Chronic hepatitis C infection: influence of the viral load, genotypes, and GBV-C/HGV coinfection on the severity of the disease in a Brazilian population. J Med Virol2002; 67: 27–32.
15.
PerezR.M., FerrazM.L., FigueiredoM.S.Unexpected distribution of hepatitis C virus genotypes in patients on hemodialysis and kidney transplant recipients. J Med Virol2003; 69: 489–494.
16.
CampiottoS., PinhoJ.R., CarrilhoF.J.Geographic distribution of hepatitis C virus genotypes in Brazil. Braz J Med Biol Res2005; 38: 41–49.
17.
MartinsR.M., TelesS.A., FreitasN.R.Distribution of hepatitis C virus genotypes among blood donors from midwest region of Brazil. Rev Inst Med Trop Sao Paulo2006; 48: 53–55.
18.
CarneiroM.A., TelesS.A., LampeE.Molecular and epidemiological study on nosocomial transmission of HCV in hemodialysis patients in Brazil. J Med Virol2007; 79: 1325–1333.
19.
FreitasS.Z., da CunhaR.V., MartinsR.M., TelesS.A., IbanhesM.L., Motta-CastroA.R.Prevalence, genotypes and risk factors associated with hepatitis C virus infection in hemodialysis patients in Campo Grande, MS, Brazil. Mem Inst Oswaldo Cruz2008; 103: 405–408.
20.
LopesC.L., TelesS.A., Espirito-SantoM.P.Prevalence, risk factors and genotypes of hepatitis C virus infection among drug users, central-western Brazil. Rev Saude Publica2009; 43Suppl 1: 43–50.
21.
OliveiraM.L., YoshidaC.F., TellesP.R.Trends in HCV prevalence, risk factors and distribution of viral genotypes in injecting drug users: findings from two cross-sectional studies. Epidemiol Infect2009; 137: 970–979.
22.
LampeE., Espirito-SantoM.P., MartinsR.M., BelloG.Epidemic history of hepatitis C virus in Brazil. Infect Genet Evol2010; 10: 886–895.
23.
RomanoC.M., de Carvalho-MelloI.M., JamalL.F.Social networks shape the transmission dynamics of hepatitis C virus. PLoS ONE2010; 5: e11170.
24.
Peres-da-SilvaA., AlmeidaA.J., LampeE.Genetic diversity of NS3 protease from Brazilian HCV isolates and possible implications for therapy with direct-acting antiviral drugs. Mem Inst Oswaldo Cruz2012; 107: 254–261.
25.
OliveiraM.L., BastosF.I., TellesP.R.Epidemiological and genetic analyses of hepatitis C virus transmission among young/short- and long-term injecting drug users from Rio de Janeiro, Brazil. J Clin Virol2009; 44: 200–206.
26.
VieiraD.S., Alvarado-MoraM.V., BotelhoL., CarrilhoF.J., PinhoJ.R., SalcedoJ.M.Distribution of hepatitis C virus (HCV) genotypes in patients with chronic infection from Rondonia, Brazil. Virol J2011; 8: 165.
27.
RibeiroL.C., SoutoF.J., do Espírito-SantoM.P., G-OliveiraR., LampeE.An autochthonous case of hepatitis C virus genotype 5a in Brazil: phylogenetic analysis. Arch Virol2009; 154: 665–670.
28.
KuikenC., YusimK., BoykinL., RichardsonR.The Los Alamos hepatitis C sequence database. Bioinformatics2005; 21: 379–384.
29.
ThompsonJ.D., GibsonT.J., PlewniakF., JeanmouginF., HigginsD.G.The CLUSTAL_X windows interface: flexible strategies for multiple sequence alignment aided by quality analysis tools. Nucleic Acids Res1997; 25: 4876–4882.
30.
GuindonS., GascuelO.A simple, fast, and accurate algorithm to estimate large phylogenies by maximum likelihood. Syst Biol2003; 52: 696–704.
31.
GuindonS., LethiecF., DurouxP., GascuelO.PHYML Online – a web server for fast maximum likelihood-based phylogenetic inference. Nucleic Acids Res2005; 33: W557–W559.
32.
RodríguezF., OliverJ.L., MarinA., MedinaJ.R.The general stochastic model of nucleotide substitution. J Theor Biol1990; 142: 485–501.
33.
PosadaD.jModelTest: phylogenetic model averaging. Mol Biol Evol2008; 25: 1253–1256.
34.
AnisimovaM., GascuelO.Approximate likelihood-ratio test for branches: a fast, accurate, and powerful alternative. Syst Biol2006; 55: 539–552.
35.
Peres-da-SilvaA., AlmeidaA.J., LampeE.Genetic diversity of NS3 protease from Brazilian HCV isolates and possible implications for therapy with direct-acting antiviral drugs. Mem Inst Oswaldo Cruz2012; 107: 254–261.
36.
BaeA., SunS.C., QiX.Susceptibility of treatment-naive hepatitis C virus (HCV) clinical isolates to HCV protease inhibitors. Antimicrob Agents Chemother2010; 54: 5288–5297.
37.
HalfonP., LocarniniS.Hepatitis C virus resistance to protease inhibitors. J Hepatol2011; 55: 192–206.
38.
LenzO., FeveryB., VijgenJ.TMC435 in patients infected with HCV genotype 1 who have failed previous pegylated interferon/ribavirin treatment: virologic analyses of the ASPIRE trial. J Hepatol2012; 56Suppl 2: S5.
