Endogenous Retroviral Envelope Syncytin Induces HIV-1 Spreading and Establishes HIV Reservoirs in Placenta.
Cell Rep
; 30(13): 4528-4539.e4, 2020 03 31.
Article
em En
| MEDLINE
| ID: mdl-32234485
ABSTRACT
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Placenta
/
Proteínas da Gravidez
/
Reservatórios de Doenças
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Produtos do Gene env
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Proteínas do Envelope Viral
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Retrovirus Endógenos
Limite:
Adult
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Female
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Humans
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Pregnancy
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article