Endogenous Retroviral Envelope Syncytin Induces HIV-1 Spreading and Establishes HIV Reservoirs in Placenta

Cell Rep. 2020 Mar 31;30(13):4528-4539.e4. doi: 10.1016/j.celrep.2020.03.016.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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 Infections / immunology
  • HIV Infections / virology
  • HIV-1 / genetics
  • HeLa Cells
  • Host-Pathogen Interactions
  • Humans
  • Placenta / virology*
  • Pregnancy
  • Pregnancy Proteins / metabolism*
  • Proviruses / metabolism
  • RNA, Viral / metabolism
  • Tissue Donors
  • Trophoblasts / pathology
  • Trophoblasts / virology
  • Tropism
  • Viral Envelope Proteins / metabolism*
  • Viral Load


  • DNA, Viral
  • Gene Products, env
  • Pregnancy Proteins
  • RNA, Viral
  • Viral Envelope Proteins
  • syncytin