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Dendritic cells efficiently transmit HIV to T Cells in a tenofovir and raltegravir insensitive manner

Kim, Jocelyn T. and Chang, Emery and Sigal, Alex and Baltimore, David (2018) Dendritic cells efficiently transmit HIV to T Cells in a tenofovir and raltegravir insensitive manner. PLoS ONE, 13 . Art. No. e0189945. ISSN 1932-6203. PMCID PMC5749731. https://resolver.caltech.edu/CaltechAUTHORS:20180108-143545755

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Abstract

Dendritic cell (DC)-to-T cell transmission is an example of infection in trans, in which the cell transmitting the virus is itself uninfected. During this mode of DC-to-T cell transmission, uninfected DCs concentrate infectious virions, contact T cells and transmit these virions to target cells. Here, we investigated the efficiency of DC-to-T cell transmission on the number of cells infected and the sensitivity of this type of transmission to the antiretroviral drugs tenofovir (TFV) and raltegravir (RAL). We observed activated monocyte-derived and myeloid DCs amplified T cell infection, which resulted in drug insensitivity. This drug insensitivity was dependent on cell-to-cell contact and ratio of DCs to T cells in coculture. DC-mediated amplification of HIV-1 infection was efficient regardless of virus tropism or origin. The DC-to-T cell transmission of the T/F strain CH077.t/2627 was relatively insensitive to TFV compared to DC-free T cell infection. The input of virus modulated the drug sensitivity of DC-to-T cell infection, but not T cell infection by cell-free virus. At high viral inputs, DC-to-T cell transmission reduced the sensitivity of infection to TFV. Transmission of HIV by DCs in trans may have important implications for viral persistence in vivo in environments, where residual replication may persist in the face of antiretroviral therapy.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1371/journal.pone.0189945DOIArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5749731/PubMed CentralArticle
https://doi.org/10.1371/journal.pone.0189945.s001DOIFig. S1
https://doi.org/10.1371/journal.pone.0189945.s002DOITable S1
https://doi.org/10.1371/journal.pone.0189945.s003DOITable S2
ORCID:
AuthorORCID
Kim, Jocelyn T.0000-0001-8723-8190
Sigal, Alex0000-0001-8571-2004
Baltimore, David0000-0001-8723-8190
Additional Information:© 2018 Kim et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Received: June 15, 2017; Accepted: December 5, 2017; Published: January 2, 2018. Data Availability Statement: All relevant data are within the paper and its Supporting Information files. This work was supported by the UCLA CTSI KL2 (KL2TR001882), National Institutes of Health (OPPGH5157), American Foundation for AIDS Research (108292-51-RGRL), UCLA/CFAR Virology Core Laboratory (5P30 AI028697), the UCLA Specialty Training and Advanced Research Program, and NIH AIDS Reagent Program. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors have declared that no competing interests exist.
Funders:
Funding AgencyGrant Number
NIHKL2TR001882
NIHOPPGH5157
American Foundation for AIDS Research108292-51-RGRL
NIH5P30 AI028697
UCLA Specialty Training and Advanced Research ProgramUNSPECIFIED
PubMed Central ID:PMC5749731
Record Number:CaltechAUTHORS:20180108-143545755
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20180108-143545755
Official Citation:Kim JT, Chang E, Sigal A, Baltimore D. (2018) Dendritic cells efficiently transmit HIV to T Cells in a tenofovir and raltegravir insensitive manner. PLoS ONE 13(1): e0189945. https://doi.org/10.1371/journal.pone.0189945
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:84173
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:08 Jan 2018 23:45
Last Modified:19 Nov 2020 20:17

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