title: Rapid and efficient cell-to-cell transmission of human immunodeficiency virus infection from monocyte-derived macrophages to peripheral blood lymphocytes.
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.
authors.affiliation: Infectious Diseases Laboratories, Institute of Medical and Veterinary Science, Frome Road, Adelaide, 5000, South Australia. jill.carr@imvs.sa.gov.au
authors.forename: J M
authors.initials: JM
authors.lastname: Carr
authors.forename: H
authors.initials: H
authors.lastname: Hocking
authors.forename: P
authors.initials: P
authors.lastname: Li
authors.forename: C J
authors.initials: CJ
authors.lastname: Burrell
mesh_terms: D002478:Cells, Cultured; D004279:DNA, Viral / Q000096:biosynthesis; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007700:Kinetics; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000821:virology*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000648:ultrastructure / Q000821:virology*; D008934:Mitogens / Q000494:pharmacology; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000821:virology; D010835:Phytohemagglutinins / Q000494:pharmacology; D013997:Time Factors
chemical_list: D004279:DNA, Viral; D008934:Mitogens; D010835:Phytohemagglutinins