Human lymphocyte apoptosis after exposure to influenza A virus

Joan Nichols, J. A. Niles, Jr Roberts N.J.

Research output: Contribution to journalArticle

74 Citations (Scopus)

Abstract

Infection of humans with influenza A virus (IAV) results in a severe transient leukopenia. The goal of these studies was to analyze possible mechanisms behind this IAV. induced leukopenia with emphasis on the potential induction of apoptosis of lymphocytes by the virus. Analysis of lymphocyte subpopulations after exposure to IAV showed that a portion of CD3+, CD4+, CD8+, and CD19+ lymphocytes became apoptotic (terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling positive). The percentage of cells that are infected was shown to be less than the percentage of apoptotic cells, suggesting that direct effects of cell infection by the virus cannot account fully for the high level of cell death. Removal of monocytes-macrophages after IAV exposure reduced the percent of lymphocytes that were apoptotic. Treatment of virus-exposed cultures with anti-tumor necrosis factor alpha did not reduce the percentage of lymphocytes that were apoptotic. In virus-exposed cultures treated with anti-FasL antibody, recombinant soluble human Fas, Ac-DEVD-CHO (caspase-3 inhibitor), or Z-VAD-FMK (general caspase inhibitor), apoptosis and production of the active form of caspase-3 was reduced. The apoptotic cells were Fas-high-density cells while the non-apoptotic cells expressed a low density of Fas. The present studies showed that Fas-FasL signaling plays a major role in the induction of apoptosis in lymphocytes after exposure to IAV. Since the host response to influenza virus commonly results in recovery from the infection, with residual disease uncommon, lymphocyte apoptosis likely represents a part of an overall beneficial immune response but could be a possible mechanism of disease pathogenesis.

Original languageEnglish (US)
Pages (from-to)5921-5929
Number of pages9
JournalJournal of Virology
Volume75
Issue number13
DOIs
StatePublished - 2001

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Influenza A virus
lymphocytes
apoptosis
Lymphocytes
Apoptosis
Caspase Inhibitors
Leukopenia
viruses
leukopenia
Viruses
Caspase 3
cells
caspase-3
infection
DNA Nucleotidylexotransferase
recombinant antibodies
Lymphocyte Subsets
Virus Diseases
Biotin
Infection

ASJC Scopus subject areas

  • Immunology

Cite this

Human lymphocyte apoptosis after exposure to influenza A virus. / Nichols, Joan; Niles, J. A.; Roberts N.J., Jr.

In: Journal of Virology, Vol. 75, No. 13, 2001, p. 5921-5929.

Research output: Contribution to journalArticle

Nichols, Joan ; Niles, J. A. ; Roberts N.J., Jr. / Human lymphocyte apoptosis after exposure to influenza A virus. In: Journal of Virology. 2001 ; Vol. 75, No. 13. pp. 5921-5929.
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