Dysregulation of the Polo-Like Kinase Pathway in CD4+ T Cells Is Characteristic of Pathogenic Simian Immunodeficiency Virus Infection

P Bostik, GL Dodd, F Villinger, AE Mayne… - Journal of …, 2004 - Am Soc Microbiol
P Bostik, GL Dodd, F Villinger, AE Mayne, AA Ansari
Journal of virology, 2004Am Soc Microbiol
ABSTRACT CD4+ T-cell dysfunction highlighted by defects within the intracellular signaling
cascade and cell cycle has long been characterized as a direct and/or indirect consequence
of human immunodeficiency virus (HIV) infection in humans and simian immunodeficiency
virus (SIV) infection in rhesus macaques (RM). Dysregulation of the M phase of the cell cycle
is a well-documented effect of HIV or SIV infection both in vivo and in vitro. In this study the
effect of SIV infection on the modulation of two important regulators of the M phase—polo …
Abstract
CD4+ T-cell dysfunction highlighted by defects within the intracellular signaling cascade and cell cycle has long been characterized as a direct and/or indirect consequence of human immunodeficiency virus (HIV) infection in humans and simian immunodeficiency virus (SIV) infection in rhesus macaques (RM). Dysregulation of the M phase of the cell cycle is a well-documented effect of HIV or SIV infection both in vivo and in vitro. In this study the effect of SIV infection on the modulation of two important regulators of the M phase—polo-like kinases Plk3 and Plk1—was investigated. We have previously shown that Plk3 is markedly downregulated in CD4+ T cells from SIV-infected disease-susceptible RM but not SIV-infected disease-resistant sooty mangabeys (SM), denoting an association of downregulation with disease progression. Here we show that, in addition to the downregulation, Plk3 exhibits aberrant activation patterns in the CD4+ T cells from SIV-infected RM following T-cell receptor stimulation. Interestingly, in vitro SIV infection of CD4+ T cells leads to the upregulation, rather than downregulation, of Plk3, suggesting that different mechanisms operate in vitro and in vivo. In addition, CD4+ T cells from RM with high viral loads exhibited consistent and significant upregulation of Plk1, concurrent with an aberrant activation-induced Plk1 response, suggesting complex mechanisms of SIV-induced M-phase abnormalities in vivo. Altogether this study presents a novel mechanism underlying M-phase defects observed in CD4+ T cells from HIV or SIV-infected disease-susceptible humans and RM which may contribute to aberrant T-cell responses and disease pathogenesis.
American Society for Microbiology