Rapid and Efficient Cell-To-Cell Transmission of Human Immunodeficiency Virus Infection From Monocyte-Derived Macrophages to Peripheral Blood Lymphocytes

Virology. 1999 Dec 20;265(2):319-29. doi: 10.1006/viro.1999.0047.

Abstract

Macrophages are considered of central importance in cell-to-cell transmission of human immunodeficiency virus (HIV) infection in vivo. In this report, we describe a novel cell-to-cell transmission model using HIV-infected monocyte-derived macrophages (MDMs) as donor cells and peripheral blood lymphocytes (PBLs) as recipients. Virus was transmitted during a 2-h coincubation period from intracellular or tightly cell-associated viral stores in adherent infected MDMs to nonadherent CD3(+) PBLs. Transmission required cell contact, but syncytia formation was not observed. HIV cell-to-cell transmission occurred in both allogeneic and autologous systems, and replication was higher in phytohemagglutinin (PHA)-stimulated than unstimulated recipient PBLs. In contrast, transmission of infection by cell-free virus was barely detectable without PHA stimulation of recipients, suggesting the cell-cell interaction may have provided stimuli to recipient cells in the cell-to-cell system. Viral DNA levels increased 5-24 h postmixing, and this increase was inhibited by pretreatment of cells with the reverse transcription inhibitor azidothymidine, indicating de novo reverse transcription was involved. Cell-to-cell transmission was more efficient than infection with cell-free virus released from donor MDMs, or 0.1 TCID(50)/cell cell-free viral challenge. This model provides a system to further investigate the mechanisms and characteristics of HIV cell-to-cell transmission between relevant primary cells that may be analogous to this important mode of virus spread in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • DNA, Viral / biosynthesis
  • HIV-1 / genetics
  • HIV-1 / physiology*
  • Humans
  • Kinetics
  • Lymphocytes / cytology
  • Lymphocytes / drug effects
  • Lymphocytes / virology*
  • Macrophages / cytology
  • Macrophages / drug effects
  • Macrophages / ultrastructure
  • Macrophages / virology*
  • Mitogens / pharmacology
  • Monocytes / cytology
  • Monocytes / drug effects
  • Monocytes / virology
  • Phytohemagglutinins / pharmacology
  • Time Factors

Substances

  • DNA, Viral
  • Mitogens
  • Phytohemagglutinins