Detailed Characterization of Early HIV-1 Replication Dynamics in Primary Human Macrophages
AbstractMacrophages are natural target cells of human immunodeficiency virus type 1 (HIV-1). Viral replication appears to be delayed in these cells compared to lymphocytes; however, little is known about the kinetics of early post-entry events. Time-of-addition experiments using several HIV-1 inhibitors and the detection of reverse transcriptase (RT) products with droplet digital PCR (ddPCR) revealed that early replication was delayed in primary human monocyte-derived macrophages of several donors and peaked late after infection. Direct imaging of reverse-transcription and pre-integration complexes (RTC/PIC) by click-labeling of newly synthesized DNA further confirmed our findings and showed a concomitant shift to the nuclear stage over time. Altering the entry pathway enhanced infectivity but did not affect kinetics of viral replication. The addition of viral protein X (Vpx) enhanced productive infection and accelerated completion of reverse transcription and nuclear entry. We propose that sterile alpha motif (SAM) and histidine/aspartate (HD) domain-containing protein 1 (SAMHD1) activity lowering deoxyribonucleotide triphosphate (dNTP) pools is the principal factor delaying early HIV-1 replication in macrophages. View Full-Text
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Bejarano, D.A.; Puertas, M.C.; Börner, K.; Martinez-Picado, J.; Müller, B.; Kräusslich, H.-G. Detailed Characterization of Early HIV-1 Replication Dynamics in Primary Human Macrophages. Viruses 2018, 10, 620.
Bejarano DA, Puertas MC, Börner K, Martinez-Picado J, Müller B, Kräusslich H-G. Detailed Characterization of Early HIV-1 Replication Dynamics in Primary Human Macrophages. Viruses. 2018; 10(11):620.Chicago/Turabian Style
Bejarano, David A.; Puertas, Maria C.; Börner, Kathleen; Martinez-Picado, Javier; Müller, Barbara; Kräusslich, Hans-Georg. 2018. "Detailed Characterization of Early HIV-1 Replication Dynamics in Primary Human Macrophages." Viruses 10, no. 11: 620.
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