Effects of human immunodeficiency virus type 1 on CD4 lymphocyte subset activation

Anna Maria Masci, Francisca Lago Paz, Adriana Borriello, Silvana Cassano, Valentina Della Pietra, Heribert Stoiber, Giuseppe Matarese, Fulvio Della Ragione, Serafino Zappacosta, Luigi Racioppi

Research output: Contribution to journalArticle

Abstract

The pathogenesis of the decline of CD4 lymphocyte counts accompanying the typical course of HIV-1 infection is not completely defined and might be related to a differential susceptibility of naive and memory cells to HIV-1 exposure. Here, we examined the effects induced by heat-inactivated HIV-1 virions on these lymphocyte populations. Exposure of CD45RA naive T cells to inactivated viral particles induced a marked decrease of both mitogenic responses and activation-induced apoptosis. Conversely, the growth of CD45RO cells was less severely restrained. Analysis of intracellular levels of cell cycle regulatory proteins revealed an arrest at the G1/S restriction point of the naive but not memory subset. This effect was associated with alterations in phosphotyrosine profile and with a marked decrease of ERK and NJK kinase activation. Finally, up-regulation of the cAMP-dependent protein kinase A (PKA) activity induced by mitogens was not affected by virus. Altogether, these findings show that interaction of HIV-1 with the T cell surface is sufficient to inhibit the proliferative response of the CD4CD45RA subset by disturbing proximal TCR signaling. This mechanism would affect renewal of naive lymphocytes, contributing in such a way to the impairment of T cell turnover during the course of HIV-1 infection.

Original languageEnglish
Pages (from-to)1879-1889
Number of pages11
JournalEuropean Journal of Immunology
Volume29
Issue number6
DOIs
Publication statusPublished - 1999

Keywords

  • cAMP
  • HIV-1
  • Lymphocyte activation
  • Naive lymphocyte
  • Protein kinase A

ASJC Scopus subject areas

  • Immunology

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  • Cite this

    Masci, A. M., Paz, F. L., Borriello, A., Cassano, S., Della Pietra, V., Stoiber, H., Matarese, G., Della Ragione, F., Zappacosta, S., & Racioppi, L. (1999). Effects of human immunodeficiency virus type 1 on CD4 lymphocyte subset activation. European Journal of Immunology, 29(6), 1879-1889. https://doi.org/10.1002/(SICI)1521-4141(199906)29:06<1879::AID-IMMU1879>3.0.CO;2-2