Journal article
Plasmacytoid dendritic cells sense HIV replication before detectable viremia following treatment interruption
The Journal of clinical investigation, v 130(6), pp 2845-2858
27 Apr 2020
PMID: 32017709
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Plasmacytoid dendritic cells (pDCs) are robust producers of IFNα and one of the first immune cells to respond to SIV infection. To elucidate responses to early HIV-1 replication, we studied blood pDCs in 29 HIV-infected participants who initiated antiretroviral therapy during acute infection and underwent analytic treatment interruption (ATI). We observed an increased frequency of partially activated pDCs in the blood before detection of HIV RNA. Concurrent with peak pDC frequency, we detected a transient decline in the ability of pDCs to produce IFNα in vitro, which correlated with decreased phosphorylation of IFN regulatory factory 7 (IRF7) and NF-κB. The levels of phosphorylated IRF7 and NF-κB inversely correlated with plasma IFNα2 levels, implying that pDCs were refractory to in vitro stimulation after IFNα production in vivo. After ATI, decreased expression of
IFN
genes in pDCs inversely correlated with the time to viral detection, suggesting that pDC
IFN
loss is part of an effective early immune response. These data from a limited cohort provide a critical first step in understanding the earliest immune response to HIV-1 and suggest that changes in blood pDC frequency and function can be used as an indicator of viral replication before detectable plasma viremia.
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Details
- Title
- Plasmacytoid dendritic cells sense HIV replication before detectable viremia following treatment interruption
- Creators
- Julie L. Mitchell - Oregon Health & Science UniversityHiroshi Takata - Gene Therapy LaboratoryRoshell Muir - Drexel UniversityDonn J. Colby - Thai Red Cross SocietyEugène Kroon - Thai Red Cross SocietyTrevor A. Crowell - Walter Reed Army Institute of ResearchCarlo Sacdalan - Thai Red Cross SocietySuteeraporn Pinyakorn - Walter Reed Army Institute of ResearchSuwanna Puttamaswin - Thai Red Cross SocietyKhunthalee Benjapornpong - Thai Red Cross SocietyRapee Trichavaroj - Armed Forces Research Institute of Medical ScienceRandall L. Tressler - National Institutes of HealthLawrence Fox - National Institutes of HealthVictoria R. Polonis - Walter Reed Army Institute of ResearchDiane L. Bolton - Walter Reed Army Institute of ResearchFrank Maldarelli - National Institutes of HealthSharon R. Lewin - Monash UniversityElias K. Haddad - Drexel UniversityPraphan Phanuphak - Thai Red Cross SocietyMerlin L. Robb - Walter Reed Army Institute of ResearchNelson L. Michael - Walter Reed Army Institute of ResearchMark de Souza - Thai Red Cross SocietyNittaya Phanuphak - US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA. Henry M. Jackson Foundation for the Advancement of Military Medicine (HJF), Bethesda, Maryland, USA. Division of Infectious Diseases and HIV Medicine, Department of Medicine, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA. South East Asia Research Collaboration with Hawaii (SEARCH), Thai Red Cross AIDS Research Centre (TRC-ARC), Bangkok, Thailand. Department of Retrovirology, Armed Forces Research Institute of Medical Sciences (AFRIMS) United States Component, Bangkok, Thailand. Division of AIDS, National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, Maryland, USA. HIV Dynamics and Replication Program, National Cancer Institute (NCI), NIH, Frederick, Maryland, USA. Peter Doherty Institute for Infection and Immunity, University of Melbourne and Royal Melbourne Hospital, Melbourne, Australia. Department of Infectious Diseases, Alfred Hospital and Monash University, Melbourne, Australia. Department of Global Health, University of Amsterdam, Amsterdam, Netherlands. The RV397, RV411, RV409, and RV254 study groups are detailed in Supplemental AcknowledgmentsJintanat Ananworanich - Walter Reed Army Institute of ResearchLydie Trautmann - Gene Therapy LaboratoryRV397, RV411, and RV254 Study Groups
- Publication Details
- The Journal of clinical investigation, v 130(6), pp 2845-2858
- Publisher
- American Society for Clinical Investigation
- Grant note
- W81XWH-07-2-0067; W81XWH-11-2-0174 / ; R01AI108433 / ;
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Infectious Diseases (and HIV Medicine)
- Web of Science ID
- WOS:000544332600025
- Scopus ID
- 2-s2.0-85085905232
- Other Identifier
- 991019167792904721
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- Collaboration types
- Industry collaboration
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Medicine, Research & Experimental