HIV-1 in human alveolar macrophages from infected patients is latent in vivo but replicates after in vitro stimulation.
It has been demonstrated that alveolar macrophages (AM) are permissive for human immunodeficiency virus (HIV-1) after in vitro infection. However, data concerning in vivo infection of AM by HIV-1 still conflict. Therefore, we investigated AM collected by bronchoalveolar lavage from 15 HIV-1-infected patients. HIV-1 p24 and Gp120 antigens and viral RNA were not detected by immunocytochemistry and in situ hybridization, respectively, using 35S-labeled 3 kb Pol-Env, 0.350 kb Gag, and 0.150 kb U5 LTR cRNA probes. In contrast, when using polymerase chain reaction on DNA extracted from purified AM, HIV-1 DNA was detected in the seven patients tested. After short-term culture of alveolar cells from three HIV-1-infected patients and in vitro stimulation with granulocyte/macrophage colony-stimulating factor (GM-CSF) and tumor necrosis factor-alpha (TNF-alpha), HIV-1 replication was observed in most of the AM. These results demonstrate that AM are latently infected by HIV-1 in vivo but are not a site for viral replication. In contrast, HIV-1 replication occurs when AM are withdrawn from their local environment, enhanced by GM-CSF and TNF-alpha stimulation. This suggests either a negative control or an inadequate stimulation of HIV-1 replication in the alveolar environment.
Lebargy
F
F
INSERM U 139, Hôpital Henri Mondor, Créteil, France.
Branellec
A
A
Deforges
L
L
Bignon
J
J
Bernaudin
J F
JF
D002460:Cell Line; D004279:DNA, Viral / Q000032:analysis; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D016655:HIV Core Protein p24 / Q000032:analysis; D015699:HIV Envelope Protein gp120 / Q000032:analysis; D015658:HIV Infections / Q000382:microbiology; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D066298:In Vitro Techniques; D016676:Macrophages, Alveolar / Q000382:microbiology*; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D017735:Virus Latency / Q000502:physiology*; D014779:Virus Replication / Q000187:drug effects / Q000502:physiology*
D004279:DNA, Viral; D016655:HIV Core Protein p24; D015699:HIV Envelope Protein gp120; D012367:RNA, Viral; D014409:Tumor Necrosis Factor-alpha; D016178:Granulocyte-Macrophage Colony-Stimulating Factor