• deep-sequencing
• fitness
• mutagens
• quasispecies
• rare haplotypes
• variability

• Humans
• Follow-Up Studies
• Mutagens
• Nucleotides
• Quasispecies/genetics
• Ribavirin/therapeutic use
• SARS-CoV-2/genetics
• Hepatitis E/drug therapy
• Hepatitis E virus/drug effects
• Hepatitis E virus/genetics

• Pla Estratègic de Recerca i Innovació en Salut (PERIS) Direcció General de Recerca i Innovació en Salut (DGRIS), Catalan Health Ministry, Generalitat de Catalunya
• IDI-20200297 Centre for Industrial Technological Development
• PI19/00301 Instituto de Salud Carlos III
• GLD21/00006 Gilead Sciences (Spain)

Direct-acting antiviral drugs to cure infections with Hepatitis C virus (HCV) achieve a sustained virological response (SVR) in more than 90% of adult patients. At present, clinical trials are ongoing and real-life data are still limited in children. Herein, we report two cases of pediatric patients treated with fixed-dose combination of sofosbuvir/ledipasvir, already approved to treat HCV4 genotype. Both young girls achieved SVR even though HCV4 isolates carried L28M and M31L NS5A resistance-associated substitutions (RASs). Therefore, possible effects of these RASs merit further study, especially in children.

• Hepatitis C virus 4
• pediatric patients
• sofosbuvir/ledipasvir

Our previous data show that hepatitis C virus (HCV) genotype 1 patients expressing the HLA-DQB1 * 0301 allele have a combined response probability of 69%, while the remaining 31% do not respond, probably because the HCV immunodominant epitope (IE) against the DQB1 * 0301 allele is mutated. HCV IE (region sequenced in NS3 is a region encoding aa 1253–1272) from 37 patients (21 Sustained Virological Response, SVR; 16 non-SVR) HLA-DQB1 * 0301+, were analysed by pyrosequencing. In vitro cultures were also determined by CD4+ proliferation, using non-mutated IE (wild-type synthetic peptide) and synthetic mutated peptide. The pyrosequencing study revealed 34 different haplotypes. The SVR patients had fewer haplotypes (P = 0.07), mutations/haplotypes (P = 0.01) and polymorphic sites (P = 0.02) than non-SVR. Three polymorphic sites were associated with the non-SVR patients: haplotype 7 (L5P); haplotype 11 (L7P); and haplotype 15, (L15S) (P = 0.02). The in vitro study (n = 7) showed that in 4/7 patients (Group 1) the CD4+ proliferation obtained with wild-type synthetic peptide was higher than that obtained with the negative control and with the synthetic mutated peptide (P = 0.039). However, in the remaining 3/7 patients (Group 2) this pattern was not observed (P = 0.7). Our findings suggest that HLA-DQB1 * 0301+ patients with high antigenic variability in HCV IE (NS31253-1272) have a lower SVR rate, due to reduced CD4+ proliferation as a result of incorrect viral HLA-Ag binding.

• anti-HCV T cell response
• hepatitis C virus
• transmission
• viral adaptation

• Diversity indices
• Gini-Simpson index
• Hill numbers
• Montserrat plots
• Mutation frequency
• Nucleotide diversity
• Quasispecies profiles
• Shannon entropy

• Biodiversity
• Ecology/methods
• Hepacivirus/classification
• Hepatitis C/virology
• Humans
• Multivariate Analysis
• Species Specificity
• Viruses/classification

It is well established that hepatitis C virus (HCV) infection and replication relies on host lipid metabolism. HCV proteins interact and associate with lipid droplets to facilitate virion assembly and production. Besides, circulating infective particles are associated with very low-density lipoprotein. On the other hand, higher serum lipid levels have been associated with sustained viral response to pegylated interferon and ribavirin therapy in chronic HCV infection, suggesting a relevant role in viral clearance for host proteins. Host and viral genetic factors play an essential role in chronic infection. Lipid metabolism is hijacked by viral infection and could determine the success of viral replication. Recently development of direct acting antiviral agents has shown a very high efficacy (> 90%) in sustained viral response rates even for cirrhotic patients and most of the viral genotypes. HCV RNA clearance induced by Sofosbuvir has been associated with an increased concentration and size of the low-density lipoprotein particles. In this review, host genetic factors, viral factors and the interaction between them will be depicted to clarify the major issues involved in viral infection and lipid metabolism.

• Hepatitis C virus
• Lipid metabolism
• Direct acting antiviral agents
• Genetic interaction
• Sofosbuvir

• Antiviral Agents/therapeutic use
• Genotype
• Hepacivirus/genetics
• Hepatitis C/drug therapy
• Hepatitis C/genetics
• Hepatitis C/metabolism
• Humans
• Lipid Metabolism

• AST
• HCV patients
• HDL-C
• male
• mtDNA copy numbers

Hepatitis C virus (HCV) infection is an important public health problem worldwide. HCV exploits complex molecular mechanisms, which result in a high degree of intrahost genetic heterogeneity. This high degree of variability represents a challenge for the accurate establishment of genetic relatedness between cases and complicates the identification of sources of infection. Tracking HCV infections is crucial for the elucidation of routes of transmission in a variety of settings. Therefore, implementation of HCV advanced molecular surveillance (AMS) is essential for disease control. Accounting for virulence is also important for HCV AMS and both viral and host factors contribute to the disease outcome. Therefore, HCV AMS requires the incorporation of host factors as an integral component of the algorithms used to monitor disease occurrence. Importantly, implementation of comprehensive global databases and data mining are also needed for the proper study of the mechanisms responsible for HCV transmission. Here, we review molecular aspects associated with HCV transmission, as well as the most recent technological advances used for virus and host characterization. Additionally, the cornerstone discoveries that have defined the pathway for viral characterization are presented and the importance of implementing advanced HCV molecular surveillance is highlighted.

• Computational Biology/methods
• Epidemiological Monitoring
• Hepacivirus/classification
• Hepacivirus/genetics
• Hepacivirus/isolation & purification
• Hepatitis C/epidemiology
• Hepatitis C/transmission
• Hepatitis C/virology
• Humans
• Molecular Epidemiology/methods

• Hepatitis C virus
• Interferon
• Mutations
• NS3
• NS4A
• NS4B