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

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. Her...

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Main Authors: Jocelyn T Kim, Emery Chang, Alex Sigal, David Baltimore
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2018-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC5749731?pdf=render
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author Jocelyn T Kim
Emery Chang
Alex Sigal
David Baltimore
author_facet Jocelyn T Kim
Emery Chang
Alex Sigal
David Baltimore
author_sort Jocelyn T Kim
collection DOAJ
description 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.
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spelling doaj.art-e798406c2b4f41f8870a1508d3e0584a2022-12-21T17:48:01ZengPublic Library of Science (PLoS)PLoS ONE1932-62032018-01-01131e018994510.1371/journal.pone.0189945Dendritic cells efficiently transmit HIV to T Cells in a tenofovir and raltegravir insensitive manner.Jocelyn T KimEmery ChangAlex SigalDavid BaltimoreDendritic 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.http://europepmc.org/articles/PMC5749731?pdf=render
spellingShingle Jocelyn T Kim
Emery Chang
Alex Sigal
David Baltimore
Dendritic cells efficiently transmit HIV to T Cells in a tenofovir and raltegravir insensitive manner.
PLoS ONE
title Dendritic cells efficiently transmit HIV to T Cells in a tenofovir and raltegravir insensitive manner.
title_full Dendritic cells efficiently transmit HIV to T Cells in a tenofovir and raltegravir insensitive manner.
title_fullStr Dendritic cells efficiently transmit HIV to T Cells in a tenofovir and raltegravir insensitive manner.
title_full_unstemmed Dendritic cells efficiently transmit HIV to T Cells in a tenofovir and raltegravir insensitive manner.
title_short Dendritic cells efficiently transmit HIV to T Cells in a tenofovir and raltegravir insensitive manner.
title_sort dendritic cells efficiently transmit hiv to t cells in a tenofovir and raltegravir insensitive manner
url http://europepmc.org/articles/PMC5749731?pdf=render
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