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Cloettapreis_2004_Nr_32

susceptibility to HIV-1 by developing in vitro systems for the standard- ized assessment of the contribution of genetic variants of selected host genes, and that would allow the genomic mapping of determinants of susceptibility to HIV-1. Figure 1: The HIV-1 life cycle. Indicated are host proteins that participate at specific steps of the replication cycle (white), and proteins acting as antiretroviral host factors (black). The first goal was approached by defining the steps in the viral life cycle that exhibit the most variation between individuals (Ciuffi, 2004). We used replicating HIV-1 and single cycle lentiviral vectors in a popu- lation approach to identify polymorphic steps during viral replication. We found that stimulated CD4 T cells (the main cellular target of HIV-1) exhibited up to 5 log unit differences in virus production. We were able to attribute up to 42% of the total variance in virus production to entry factors, and 48% to post-entry steps. Efficacy at key intracellular steps of the replicative cycle (reverse transcription, integration, trans- 20 Integration Nuclear translocation Reverse Transcription Assembly and Budding RNA Transcription Translation Regulatory, Structural and Enzymatic proteins HMGI(Y) BAF NHEJ system LEDGF PPIADC-SIGN YY1 CD4 CCR5 CXCR4 PML NF-kB NFAT Cdk9 Cyclin T1 INI1 P-TEF-b ASF/SF2 CRM1 /exportin-1 RanGTP Tsg101 AIP/ALIX HP68 Vps4 AP-2 NBP1 TASK1 βTrCP Skp1p ASK-1 PPIA MAP kinase V-ATPase APOBEC3G APOBEC3F TRIM5α Murr1 Proteasome

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