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Plasmacytoid dendritic cells sense HIV replication before detectable viremia following treatment interruption

  1. Author:
    Mitchell, Julie L.
    Takata, Hiroshi
    Muir, Roshell
    Colby, Donn J.
    Kroon, Eugene
    Crowell, Trevor A.
    Sacdalan, Carlo
    Pinyakorn, Suteeraporn
    Puttamaswin, Suwanna
    Benjapornpong, Khunthalee
    Trichavaroj, Rapee
    Tressler, Randall L.
    Fox, Lawrence
    Polonis, Victoria R.
    Bolton, Diane L.
    Maldarelli,Frank
    Lewin, Sharon R.
    Haddad, Elias K.
    Phanuphak, Praphan
    Robb, Merlin L.
    Michael, Nelson L.
    de Souza, Mark
    Phanuphak, Nittaya
    Ananworanich, Jintanat
    Trautmann, Lydie

  2. Author Address

    Walter Reed Army Inst Res, US Mil HIV Res Program, Silver Spring, MD USA.Henry M Jackson Fdn Adv Mil Med HJF, Bethesda, MD USA.Drexel Univ, Coll Med, Div Infect Dis & HIV Med, Dept Med, Philadelphia, PA 19104 USA.Thai Red Cross AIDS Res Ctr TRC Arc, South East Asia Res Collaborat Hawaii SEARCH, Bangkok, Thailand.Armed Forces Res Inst Med Sci AFRIMS United State, Dept Retrovirol, Bangkok, Thailand.NIAID, Div AIDS, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.NCI, HIV Dynam & Replicat Program, NIH, Frederick, MD 21701 USA.Univ Melbourne, Peter Doherty Inst Infect & Immun, Melbourne, Vic, Australia.Royal Melbourne Hosp, Melbourne, Vic, Australia.Alfred Hosp, Dept Infect Dis, Melbourne, Vic, Australia.Monash Univ, Melbourne, Vic, Australia.Univ Amsterdam, Dept Global Hlth, Amsterdam, Netherlands.Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Hillsboro, OR USA.Bill & Melinda Gates Med Res Inst, Cambridge, MA USA.
    1. Year: 2020
    2. Date: JUN 1
  2. Journal: JOURNAL OF CLINICAL INVESTIGATION
  3. AMER SOC CLINICAL INVESTIGATION INC,
    1. 130
    2. 6
    3. Pages: 2845-2858
  5. Type of Article: Article
  6. ISSN: 0021-9738
  1. Abstract:

    Plasmacytoid dendritic cells (pDCs) are robust producers of IFN alpha 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 IFN alpha in vitro, which correlated with decreased phosphorylation of IFN regulatory factory 7 (IRF7) and NF-kappa B. The levels of phosphorylated IRF7 and NF-kappa B inversely correlated with plasma IFN alpha 2 levels, implying that pDCs were refractory to in vitro stimulation after IFN alpha 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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External Sources

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  2. DOI: 10.1172/JCI130597
  3. View record in Web of Science®
  4. WOS: 000544332600025

Library Notes

  1. Fiscal Year: FY2019-2020
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