Biology subjects

Abecasis, A.

Publications and source records attributed to Abecasis, A..

5 recordsLinked to original sources

bioRxiv2019

An updated genotype classification system for Zika viruses

Despite the Zika virus rapid spread throughout the Americas in 2015, its phylogenetic classification is limited to either an African or Asian genotype. This classification no longer reflects the present genetic diversity of circulating strains and their geographic reach. Using 414 publicly available Zika virus genomes from 40 different countries, we created alignments of different genomic fragments with high phylogenetic signal and used these to construct multiple maximum likelihood trees (IQTree). We observed groups of strains from three major geographic regions that consistently cluster into monophyletic clades: African (AF), Asian (AS) and American (AM), the latter of which cluster into four further sub-clades: Caribbean (C), South American (SA1 and SA2) and Central American (CA). The inter-genetic distances of these clades are all significantly greater than their intra-genetic distances (p=0.05). A decision demonstrates that only five nucleotide positions are needed to correctly classify 90% of our dataset into the newly described genotypes.

genomics↗

bioRxiv2019

Drivers of HIV-1 transmission: the Portuguese case

BackgroundPortugal has one of the most severe HIV-1 epidemic in Western Europe. Two subtypes circulate in parallel since the beginning of the epidemic. Comparing their transmission patterns and its association with transmitted drug resistance (TDR) is important to pinpoint transmission hotspots and to develop evidence-based treatment guidelines.\n\nMethods3599 HIV-1 naive patients collected between 2001 and 2014 were included in the study. Sequences obtained from drug resistance testing were used for subtyping, TDR determination and transmission clusters (TC) analyses.\n\nResultsSubtype B transmission was significantly associated with young males, while subtype G was associated with older heterosexuals. Young males infected with subtype B were more likely to be included in TC. Consistently, a decreasing trend of prevalence and transmission of subtype G in Portuguese originated people was observed. Active TCs were associated with subtype B-infected males residing in Lisbon. TDR was significantly different when comparing subtypes B (10.8% [9.5-12.2]) and G (7.6% [6.4-9.0]) (p=0.001).\n\nDiscussionTC analyses shows that the subtype B epidemic is active and fueled by young male patients residing in Lisbon and that transmission of subtype G in Portugal is decreasing. Despite similar treatment rates for both subtypes in Portugal, TDR is different between subtypes.

molecular biology↗

bioRxiv2019

An evolutionary-based approach to quantify the genetic barrier to drug resistance in fast-evolving viruses: an application to HIV-1 subtypes and integrase inhibitors

Viral pathogens causing global disease burdens are often characterised by high rates of evolutionary changes, facilitating escape from therapeutic or immune selective pressure. Extensive viral diversity at baseline can shorten the time to resistance emergence and alter mutational pathways, but the impact of genotypic background on the genetic barrier can be difficult to capture, in particular for antivirals in experimental stages, recently approved or expanded into new settings. We developed an evolutionary-based counting method to quantify the population genetic potential to resistance and assess differences between populations. We demonstrate its applicability to HIV-1 integrase inhibitors, as their increasing use globally contrasts with limited availability of non-B subtype resistant sequences and corresponding knowledge gap on drug resistance. A large sequence dataset encompassing most prevailing subtypes and resistance mutations of first- and second-generation inhibitors were investigated. A varying genetic potential for resistance across HIV-1 subtypes was detected for 15 mutations at 12 positions, with notably 140S in subtype B, while 140C was discarded to vary across subtypes. An additional analysis for HIV-1 reverse transcriptase inhibitors identified a higher potential for 65R in subtype C, on the basis of a differential codon usage not reported before. The evolutionary interpretation of genomic differences for antiviral treatment remains challenging. Our framework advances existing counting methods with an increased sensitivity that identified novel subtype dependencies as well as rejected previous statements. Future applications include novel HIV-1 drug classes as well as other viral pathogens.

microbiology↗

bioRxiv2018

VIRULIGN: fast codon-correct alignment and annotation of viral genomes

Virus sequence data are an essential resource for reconstructing spatiotemporal dynamics of viral spread as well as to inform treatment and prevention strategies. However, the potential benefit for these applications critically depends on accurate and correctly annotated alignments of genetically heterogeneous data. VIRULIGN was built for fast codoncorrect alignments of large datasets, with standardized genome annotation and various alignment export formats.\n\nVIRULIGN is freely available at https://github.com/rega-cev/virulign as an open source software project.

bioinformatics↗

bioRxiv2017

The impact of HIV-1 within-host evolution on transmission dynamics

The adaptive potential of HIV-1 is a vital mechanism to evade host immune responses and antiviral treatment. However, high evolutionary rates during persistent infection can impair transmission efficiency and alter disease progression in the new host, resulting in a delicate trade-off between within-host virulence and between-host infectiousness. This trade-off is visible in the disparity in evolutionary rates at within-host and between-host levels, and preferential transmission of ancestral donor viruses. Understanding the impact of within-host evolution for epidemiological studies is essential for the design of preventive and therapeutic measures. Herein, we review recent theoretical and experimental work that generated new insights into the complex link between within-host evolution and between-host fitness, revealing temporal and selective processes underlying the structure and dynamics of HIV-1 transmission.

microbiology↗