CHORUS Deliverable 2.1: State of the Art on Multimedia Search Engines

Based on the information provided by European projects and national initiatives related to multimedia search as well as domains experts that participated in the CHORUS Think-thanks and workshops, this document reports on the state of the art related to multimedia content search from, a technical, and socio-economic perspective. The technical perspective includes an up to date view on content based indexing and retrieval technologies, multimedia search in the context of mobile devices and peer-to-peer networks, and an overview of current evaluation and benchmark inititiatives to measure the performance of multimedia search engines. From a socio-economic perspective we inventorize the impact and legal consequences of these technical advances and point out future directions of research

URACILATED HIV-1 DNA FOLLOWS DIVERSE FATES DURING INFECTION OF MYELOID LINEAGE CELLS

The uracil nucleobase plays a central role in intrinsic immunity against HIV-1 infection when it is found in DNA rather than RNA. The most well characterized uracil-centric innate immune response involves host DNA cytidine deaminase enzymes (APOBECs), which selectively deaminate cytosine residues during HIV-1 first strand DNA synthesis thereby rendering the viral genome nonfunctional by hypermutation (G→A). Previous work from our group suggested the presence of another uracil-dependent HIV-1 restriction pathway that does not involve APOBEC enzymes. The function of this pathway, which has been historically controversial, involves incorporation of dUTP into viral DNA by reverse transcriptase to produce U/A base pairs (uracilation), which preserve the coding potential of native T/A pairs. Notably, U/A pairs are “invisible” to normal DNA sequencing methods and their presence, persistence and ultimate fate in proviral DNA of HIV-1 infected cells is an important aspect of viral infection that has been largely unexplored. The limiting dNTP pool levels and unique DNA repair capacities of non-dividing cells such as monocytes, macrophages and dendritic cells provides a distinctive and poorly understood environment for HIV replication and infection. This work describes new methods for detecting uracil bases in HIV-1 DNA and provides a detailed examination of their fate over the course of infection in monocyte-derived macrophage (MDM) target cells of HIV-1. We report that a major subpopulation of MDMs has a metabolic phenotype leading to high levels of dUTP incorporation into HIV-1 DNA (U/A pairs) during reverse transcription. Importantly, U/A base pairs are detected in short-lived blood monocytes and alveolar macrophages (but not CD4+ T cells) from antiretroviral therapy (ART)-suppressed HIV-1 infected individuals suggesting that they arise from recent passage of monocytes through a drug resistant viral reservoir. The findings define a restriction/persistence pathway that operates in monocytes, macrophages and perhaps other myeloid lineage cells, but not in CD4+ T cells. This newly defined interplay between host dNTP pools, DNA repair machinery and HIV-1 is important for understanding the potential of tissue macrophages to establish and maintain a long-term HIV reservoir