Suchergebnisse

Phylogenetic studies have contributed to our understanding of the early epidemic onset of HIV-1 in the Democratic Republic of Congo (DRC); however, the factors driving its early emergence and establishment in human populations still remain unresolved. In order to determine the key aspects of its successful epidemic spread, complete genome data are required from samples representative of the viral diversity in the DRC. In this study, we have established a universal PCR-assay that uses seven different panels of primers to produce overlapping amplicons covering the complete HIV genome. To circumvent the limitations of purifying these fragments and sequencing them with traditional approaches, we have developed a massive parallel sequencing method and a protocol for efficiently assembling HIV-1 genomes. A total of thirty-six samples, collected between 1997 and 2001 from different locations across the DRC, have been obtained, and, at this stage, we are focusing on complementing our dataset with more archival samples that can be used as HIV 'molecular fossils'. By generating complete genome phylogeographic data from the DRC, we aim to create a genomic window into the past evolutionary and epidemiological dynamics of HIV-1 in Central Africa and understand the natural history of this devastating pandemic.

Demographic change exerts pressure on public finances and labour markets. In this study, we analyse the demographic dynamics in the European Union (EU) up until 2100 and present different strategies to cope with the challenge of ageing (building on Groot and Peeters 2012, and Peeters and Groot 2012). The aim of this study is to investigate whether the EU economies, currently under fiscal distress due to the financial crisis, will be able to cope with the fiscal impact of the retiring baby boom generations in the decades to come. This impact does not only involve the public budget for the society as a whole, but also the fiscal burden for the actual workers who, in the EU social security systems, mainly pay for the old age pension benefits of the current old age generations. In our analyses of the policy options, we explicitly take account of these workers by imposing a no-change in fiscal pressure for these workers from 2010 onwards.

In earlier work, human immunodeficiency virus type 1 (HIV-1) sequences were analysed to estimate the timing of the ancestral sequence of the main group of HIV-1, the virus that is responsible for the acquired immune deficiency syndrome pandemic, yielding a best estimate of 1931 (95% confidence interval of 1915-1941). That work will be briefly reviewed, outlining how phylogenetic tools were extended to incorporate improved evolutionary models, how the molecular clock model was adapted to incorporate variable periods of latency, and how the approach was validated by correctly estimating the timing of two historically documented dates. The advantages, limitations, and assumptions of the approach will be summarized, with particular consideration of the implications of branch length uncertainty and recombination. We have recently undertaken new phylogenetic analysis of an extremely diverse set of human immunodeficiency virus envelope sequences from the Democratic Republic of the Congo (the DRC, formerly Zaire). This analysis both corroborates and extends the conclusions of our original study. Coalescent methods were used to infer the demographic history of the HIV-1 epidemic in the DRC, and the results suggest an increase in the exponential growth rate of the infected population through time.

Molecular epidemiological studies revealed that the epicenter of the HIV pandemic was Kinshasa, the capital city of the Democratic Republic of the Congo (DRC) in Central Africa. All known subtypes and numerous complex recombinant strains co-circulate in the DRC. Moreover, high intra-subtype diversity has been also documented. During two previous surveys on HIV-1 antiretroviral drug resistance in the DRC, we identified two divergent subtype C lineages in the protease and partial reverse transcriptase gene regions. We sequenced eight near full-length genomes and classified them using bootscanning and likelihood-based phylogenetic analyses. Four strains are more closely related to subtype C although within the range of inter sub-subtype distances. However, these strains also have small unclassified fragments and thus were named CRF92_C2U. Another strain is a unique recombinant of CRF92_C2U with an additional small unclassified fragment and a small divergent subtype A fragment. The three remaining strains represent a complex mosaic named CRF93_cpx. CRF93_cpx have two fragments of divergent subtype C sequences, which are not conventional subtype C nor the above described C2, and multiple divergent subtype A-like fragments. We then inferred the time-scaled evolutionary history of subtype C following a Bayesian approach and a partitioned analysis using major genomic regions. CRF92_C2U and CRF93_cpx had the most recent common ancestor with conventional subtype C around 1932 and 1928, respectively. A Bayesian demographic reconstruction corroborated that the subtype C transition to a faster phase of exponential growth occurred during the 1950s. Our analysis showed considerable differences between the newly discovered early-divergent strains and the conventional subtype C and therefore suggested that this virus has been diverging in humans for several decades before the HIV/M diversity boom in the 1950s.