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

• Verfasst von: Bejarano Acuña, David Alejandro [VerfasserIn]
• Verfasst von: Börner, Kathleen [VerfasserIn]
• Verfasst von: Müller, Barbara [VerfasserIn]
• Verfasst von: Kräusslich, Hans-Georg [VerfasserIn]
• Titel: Detailed characterization of early HIV-1 replication dynamics in primary human macrophages
• Verf.angabe: David Alejandro Bejarano, Maria C. Puertas, Kathleen Börner, Javier Martinez-Picado, Barbara Müller and Hans-Georg Kräusslich
• E-Jahr: 2018
• Jahr: 10 November 2018
• Umfang: 25 S.
• Fussnoten: Gesehen am 20.11.2018
• Titel Quelle: Enthalten in: Viruses
• Ort Quelle: Basel : MDPI, 2009
• Jahr Quelle: 2018
• Band/Heft Quelle: 10(2018,11) Artikel-Nummer 620, 25 Seiten
• ISSN Quelle: 1999-4915
• DOI: doi:10.3390/v10110620
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: human immunodeficiency virus
• Sach-SW: pre-integration complex
• Sach-SW: primary macrophages
• Sach-SW: replication kinetics
• Sach-SW: reverse-transcription complex
• Sach-SW: SAMHD1
• K10plus-PPN: 1583895442
• K10plus-PPN:
  Universitätsbibliothek
• Lokale URL UB: Zum Volltext

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.