Infection, apoptosis, and killing of mature human eosinophils by human immunodeficiency virus-1.
Although human eosinophils express low concentrations of CD4, the capacity of mature, non-replicating eosinophils to be infected with human immunodeficiency virus-1 (HIV-1) has not been established. Using peripheral blood eosinophils isolated free of contaminating lymphocytes and mononuclear leukocytes, we evaluated eosinophil infection with HIV-1. Eosinophils could be infected with strains of HIV-1 as evidenced by HIV-induced cytolytic effects, progressive release of p24 antigen in cultures of infected eosinophils, recovery of HIV from infected eosinophils by co-cultivation, and detection of HIV-1 gag viral DNA from infected eosinophils by polymerase chain reaction (PCR) amplification. Greater p24 antigen release from infected eosinophils was elicited by the phorbol ester, PMA; and eosinophil killing by HIV-1 was enhanced by the cytokine GM-CSF. By light and electron microscopy, HIV-infected eosinophils demonstrated apoptosis and necrosis. Apoptotic subdiploid nuclear staining was detected by flow cytometric analyses of propidium iodide-stained nuclei from HIV-infected eosinophils, and DNA isolated from HIV-infected eosinophils showed both nucleosomal fragmentation and diffuse degradation. Thus, mature eosinophils, non-replicating terminally differentiated leukocytes, can be infected with HIV-1. HIV-1 expression in eosinophils is promoted by increased granulocyte-macrophage colony-stimulating factor (GM-CSF) and can cause eosinophils to undergo death due to apoptosis and necrosis.
Weller
P F
PF
Department of Medicine, Harvard Thorndike Laboratories, Charles A. Dana Research Institute, Beth Israel Hospital, Harvard Medical School, Boston, Massachusetts 02215, USA.
Marshall
W L
WL
Lucey
D R
DR
Rand
T H
TH
Dvorak
A M
AM
Finberg
R W
RW
D017209:Apoptosis; D001483:Base Sequence; D002478:Cells, Cultured; D004249:DNA Damage; D017931:DNA Primers / Q000737:chemistry; D004279:DNA, Viral / Q000378:metabolism; D004804:Eosinophils / Q000382:microbiology*; D015750:Genes, gag; D016655:HIV Core Protein p24 / Q000378:metabolism; D015658:HIV Infections / Q000473:pathology*; D015497:HIV-1 / Q000254:growth & development / Q000472:pathogenicity*; D006801:Humans; D008969:Molecular Sequence Data; D009336:Necrosis
D017931:DNA Primers; D004279:DNA, Viral; D016655:HIV Core Protein p24