Rapid and efficient cell-to-cell transmission of human immunodeficiency virus infection from monocyte-derived macrophages to peripheral blood lymphocytes

Macrophages are considered of central importance in cell-to-cell transmissi on of human immunodeficiency virus (HIV) infection in vivo. In this report, we describe a novel cell-to-cell transmission model using HIV-infected mon ocyte-derived macrophages (MDMs) as donor cells and peripheral blood lympho cytes (PBLs) as recipients. Virus was transmitted during a 2-h coincubation period from intracellular or tightly cell-associated viral stores in adher ent infected MDMs to nonadherent CD3(+) PBLs. Transmission required cell co ntact, but syncytia formation was not observed. HIV cell-to-cell transmissi on occurred in both allogeneic and autologous systems, and replication was higher in phytohemagglutinin (PHA)-stimulated than unstimulated recipient P BLs. In contrast, transmission of infection by cell-free virus was barely d etectable without PHA stimulation of recipients, suggesting the cell-cell i nteraction may have provided stimuli to recipient cells in the cell-to-cell system. Viral DNA levels increased 5-24 h postmixing, and this increase wa s inhibited by pretreatment of cells with the reverse transcription inhibit or azidothymidine, indicating de novo reverse transcription was involved. C ell-to-cell transmission was more efficient than infection with cell-free v irus released from donor MDMs, or 0.1 TCID50/cell cell-free viral challenge . This model provides a system to further investigate the mechanisms and ch aracteristics of HIV cell-to-cell transmission between relevant primary cel ls that may be analogous to this important mode of virus spread in vivo. (C ) 1999 Academic Press.