Cell-to-cell transmission of HIV-1 and HIV-2 from infected macrophages and dendritic cells to CD4+ T lymphocytes

Marta Calado, David Pires, Carolina Conceição, Rita Ferreira, Quirina Santos-Costa, Elsa Anes, José Miguel Azevedo-Pereira*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)
19 Downloads

Abstract

Macrophages (Mø) and dendritic cells (DCs) are key players in human immunodeficiency virus (HIV) infection and pathogenesis. They are essential for the spread of HIV to CD4+ T lymphocytes (TCD4+) during acute infection. In addition, they constitute a persistently infected reservoir in which viral production is maintained for long periods of time during chronic infection. Defining how HIV interacts with these cells remains a critical area of research to elucidate the pathogenic mechanisms of acute spread and sustained chronic infection and transmission. To address this issue, we analyzed a panel of phenotypically distinct HIV-1 and HIV-2 primary isolates for the efficiency with which they are transferred from infected DCs or Mø to TCD4+. Our results show that infected Mø and DCs spread the virus to TCD4+ via cell-free viral particles in addition to other alternative pathways. We demonstrate that the production of infectious viral particles is induced by the co-culture of different cell populations, indicating that the contribution of cell signaling driven by cell-to-cell contact is a trigger for viral replication. The results obtained do not correlate with the phenotypic characteristics of the HIV isolates, namely their co-receptor usage, nor do we find significant differences between HIV-1 and HIV-2 in terms of cis- or trans-infection. The data presented here may help to further elucidate the cell-to-cell spread of HIV and its importance in HIV pathogenesis. Ultimately, this knowledge is critical for new therapeutic and vaccine approaches.

Original languageEnglish
Article number1030
Number of pages18
JournalViruses
Volume15
Issue number5
DOIs
Publication statusPublished - 22 Apr 2023

Keywords

  • Acute infection
  • Cis-infection
  • Dendritic cells
  • HIV
  • Macrophages
  • Trans-infection
  • Transmission

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