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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Masci, AM; Paz, FL; Borriello, A; Cassano, S; Della Pietra, V; Stoiber, H; Matarese, G; Della Ragione, F; Zappacosta, S; Racioppi, L

Published Date

  • June 1999

Published In

Volume / Issue

  • 29 / 6

Start / End Page

  • 1879 - 1889

PubMed ID

  • 10382750

Pubmed Central ID

  • 10382750

Electronic International Standard Serial Number (EISSN)

  • 1521-4141

International Standard Serial Number (ISSN)

  • 0014-2980

Digital Object Identifier (DOI)

  • 10.1002/(sici)1521-4141(199906)29:06<1879::aid-immu1879>3.0.co;2-2

Language

  • eng