Endogenous Retroviral Envelope Syncytin Induces HIV-1 Spreading and Establishes HIV Reservoirs in Placenta.
Adult
Antiretroviral Therapy, Highly Active
CD4-Positive T-Lymphocytes
/ virology
Cell Fusion
DNA, Viral
/ genetics
Disease Reservoirs
/ virology
Endogenous Retroviruses
/ metabolism
Female
Gene Products, env
/ metabolism
HIV Infections
/ drug therapy
HIV-1
/ genetics
HeLa Cells
Host-Pathogen Interactions
Humans
Placenta
/ virology
Pregnancy
Pregnancy Proteins
/ metabolism
Proviruses
/ metabolism
RNA, Viral
/ metabolism
Tissue Donors
Trophoblasts
/ pathology
Tropism
Viral Envelope Proteins
/ metabolism
Viral Load
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
31 03 2020
31 03 2020
Historique:
received:
10
10
2019
revised:
16
01
2020
accepted:
05
03
2020
entrez:
3
4
2020
pubmed:
3
4
2020
medline:
27
3
2021
Statut:
ppublish
Résumé
Radical cure of HIV-1 (HIV) is hampered by the establishment of HIV reservoirs and persistent infection in deep tissues despite suppressive antiretroviral therapy (ART). Here, we show that among HIV-positive women receiving suppressive ART, cells from placental tissues including trophoblasts contain HIV RNA and DNA. These viruses can be reactivated by latency reversal agents. We find that syncytin, the envelope glycoprotein of human endogenous retrovirus family W1 expressed on placental trophoblasts, triggers cell fusion with HIV-infected T cells. This results in cell-to-cell spread of HIV to placental trophoblasts. Such cell-to-cell spread of HIV is less sensitive to ART than free virus. Replication in syncytin-expressing cells can also produce syncytin-pseudotyped HIV, further expanding its ability to infect non-CD4 cells. These previously unrecognized mechanisms of HIV entry enable the virus to bypass receptor restriction to infect host barrier cells, thereby facilitating viral transmission and persistent infection in deep tissues.
Identifiants
pubmed: 32234485
pii: S2211-1247(20)30323-5
doi: 10.1016/j.celrep.2020.03.016
pmc: PMC7770760
mid: NIHMS1654996
pii:
doi:
Substances chimiques
DNA, Viral
0
Gene Products, env
0
Pregnancy Proteins
0
RNA, Viral
0
Viral Envelope Proteins
0
syncytin
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4528-4539.e4Subventions
Organisme : NIAID NIH HHS
ID : R01 AI077505
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI126619
Pays : United States
Organisme : NIAID NIH HHS
ID : DP1 AI106275
Pays : United States
Organisme : NIH HHS
ID : DP1 OD008243
Pays : United States
Organisme : NIAID NIH HHS
ID : P30 AI110527
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002243
Pays : United States
Organisme : NIAID NIH HHS
ID : P30 AI050410
Pays : United States
Informations de copyright
Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests The authors declare no competing interests.
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