Publications
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1a/1b Subtype Profiling of Nonnucleoside Polymerase Inhibitors of Hepatitis C Virus. Vrije Universiteit Brussel
The RNA-dependent RNA polymerase (NS5B) of hepatitis C virus (HCV) is an unusually attractive target for drug discovery since it contains five distinct drugable sites. The success of novel antiviral therapies will require nonnucleoside inhibitors to be active in at least patients infected with HCV of subtypes 1a and 1b. Therefore, the genotypic assessment of these agents against clinical isolates derived from genotype 1-infected patients is an ...
Characterization of Nucleoside Reverse Transcriptase Inhibitor-Associated Mutations in the RNase H Region of HIV-1 Subtype C Infected Individuals Vrije Universiteit Brussel KU Leuven
The South African national treatment programme includes nucleoside reverse transcriptase inhibitors (NRTIs) in both first and second line highly active antiretroviral therapy regimens. Mutations in the RNase H domain have been associated with resistance to NRTIs but primarily in HIV-1 subtype B studies. Here, we investigated the prevalence and association of RNase H mutations with NRTI resistance in sequences from HIV-1 subtype C infected ...
Central nervous system compartmentalization of HIV-1 subtype C variants early and late in infection in young children University of Antwerp
HIV-1 subtype B replication in the CNS can occur in CD4+ T cells or macrophages/microglia in adults. However, little is known about CNS infection in children or the ability of subtype C HIV-1 to evolve macrophage-tropic variants. In this study, we examined HIV-1 variants in ART-naive children aged three years or younger to determine viral genotypes and phenotypes associated with HIV-1 subtype C pediatric CNS infection. We examined HIV-1 subtype ...
Contribution of epidemiological predictors in unraveling the phylogeographic history of HIV-1 subtype C in Brazil KU Leuven
The phylogeographic history of the Brazilian HIV-1 subtype C (HIV-1C) epidemic is still unclear. Previous studies have mainly focused on the capital cities of Brazilian federal states, and the fact that HIV-1C infections increase at a higher rate than subtype B infections in Brazil calls for a better understanding of the process of spatial spread. A comprehensive sequence data set sampled across 22 Brazilian locations was assembled and analyzed. ...
Optimizing ancestral trait reconstruction of large HIV Subtype C datasets through multiple-trait subsampling KU Leuven
Large datasets along with sampling bias represent a challenge for phylodynamic reconstructions, particularly when the study data are obtained from various heterogeneous sources and/or through convenience sampling. In this study, we evaluate the presence of unbalanced sampled distribution by collection date, location, and risk group of human immunodeficiency virus Type 1 Subtype C using a comprehensive subsampling strategy and assess their impact ...
Impact of virus subtype and host IFNL4 genotype on large-scale RNA structure formation in the genome of hepatitis C virus KU Leuven
Mechanisms underlying the ability of hepatitis C virus (HCV) to establish persistent infections and induce progressive liver disease remain poorly understood. HCV is one of several positive-stranded RNA viruses capable of establishing persistence in their immunocompetent vertebrate hosts, an attribute previously associated with formation of large-scale RNA structure in their genomic RNA. We developed novel methods to analyze and visualize ...
Increasing importance of European lineages in seeding the hepatitis C virus subtype 1a epidemic in Spain KU Leuven
BackgroundReducing the burden of the hepatitis C virus (HCV) requires large-scale deployment of intervention programmes, which can be informed by the dynamic pattern of HCV spread. In Spain, ongoing transmission of HCV is mostly fuelled by people who inject drugs (PWID) infected with subtype 1a (HCV1a).AimOur aim was to map how infections spread within and between populations, which could help formulate more effective intervention programmes to ...
Implications of hepatitis C virus subtype 1a migration patterns for virus genetic sequencing policies in Italy KU Leuven
BACKGROUND: In-depth phylogeographic analysis can reveal migration patterns relevant for public health planning. Here, as a model, we focused on the provenance, in the current Italian HCV subtype 1a epidemic, of the NS3 resistance-associated variant (RAV) Q80K, known to interfere with the action of NS3/4A protease inhibitor simeprevir. HCV1a migration patterns were analysed using Bayesian phylodynamic tools, capitalising on newly generated and ...