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Viruses 2018, 10(11), 620; https://doi.org/10.3390/v10110620

Detailed Characterization of Early HIV-1 Replication Dynamics in Primary Human Macrophages

1
Department of Infectious Diseases, Virology, University of Heidelberg, 69120 Heidelberg, Germany
2
AIDS Research Institute IrsiCaixa, Institut d’Investigació en Cièncias de la Salut Germans Trias i Pujol, Universitat Autònoma de Barcelona, 08916 Badalona, Spain
3
German Center for Infection Research, Partner Site Heidelberg, 69120 Heidelberg, Germany
4
Faculty of Medicine, University of Vic—Central University of Catalonia (UVic-UCC), 08500 Vic, Spain
5
Catalan Institution for Research and Advanced Studies (ICREA), 08010 Barcelona, Spain
*
Author to whom correspondence should be addressed.
Received: 12 October 2018 / Revised: 2 November 2018 / Accepted: 5 November 2018 / Published: 10 November 2018
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Abstract

Macrophages 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
Keywords: human immunodeficiency virus; primary macrophages; reverse-transcription complex; pre-integration complex; replication kinetics; SAMHD1 human immunodeficiency virus; primary macrophages; reverse-transcription complex; pre-integration complex; replication kinetics; SAMHD1
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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.

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