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Detailed characterization of early HIV-1 replication dynamics in primary human macrophages

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...

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Bibliographic Details
Main Authors: Bejarano Acuña, David Alejandro (Author) , Börner, Kathleen (Author) , Müller, Barbara (Author) , Kräusslich, Hans-Georg (Author)
Format: Article (Journal)
Language:English
Published: 10 November 2018
In: Viruses
Year: 2018, Volume: 10, Issue: 11
ISSN:1999-4915
DOI:10.3390/v10110620
Online Access:Verlag, kostenfrei, Volltext: http://dx.doi.org/10.3390/v10110620
Verlag, kostenfrei, Volltext: https://www.mdpi.com/1999-4915/10/11/620
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Author Notes:David Alejandro Bejarano, Maria C. Puertas, Kathleen Börner, Javier Martinez-Picado, Barbara Müller and Hans-Georg Kräusslich
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Summary: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.
Item Description:Gesehen am 20.11.2018
Physical Description:Online Resource
ISSN:1999-4915
DOI:10.3390/v10110620

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