Detailed Characterization of Early HIV-1 Replication Dynamics in Primary Human Macrophages
Bejarano, David Alejandro (Department of Infectious Diseases, Virology. University of Heidelberg. Heidelberg, Germany)
Puertas, Maria C.. (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Börner, Kathleen (German Center for Infection Research, Partner Site Heidelberg. Heidelberg, Germany)
Martinez-Picado, Javier (Institució Catalana de Recerca i Estudis Avançats)
Müller, Barbara (Department of Infectious Diseases, Virology, University of Heidelberg. Heidelberg, Germany)
Kräusslich, Hans-Georg (German Center for Infection Research, Partner Site Heidelberg. Heidelberg, Germany)

Date:	2018
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.
Note:	Altres ajuts: DFG/SFB1129/5(HGK)
Note:	Altres ajuts: DFG/SFB1129/6(BM)
Note:	Altres ajuts: DFG/Kr906/8-1(HGK)
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; Versió publicada
Subject:	Human immunodeficiency virus ; Primary macrophages ; Reverse-transcription complex ; Pre-integration complex ; Replication kinetics ; SAMHD1
Published in:	Viruses, Vol. 10 (november 2018) , ISSN 1999-4915

DOI: 10.3390/v10110620
PMID: 30423802

25 p, 2.8 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
Articles > Published articles