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Stress protein modulation in HIV-1 infected CD4-expressing cells

Heat shock or stress proteins (HSPs), are a large family of phylogenetically conserved molecules that can be constitutively expressed at high levels under normal physiological conditions. These proteins are selectively synthesized following metabolic and environmental insult. This study was designed to determine whether cognate and/or inducible HSP production are altered in CD4-expressing lymphocytic cell lines concomitant with acute and chronic human immunodeficiency virus type 1 (HIV-l) infection. Our findings indicate that in CEM.NKR cells, HSP27 production is selectively altered at early stages of acute HIV-infection (6-24h post-infection), subsequent to virus internalization but prior to synthesis of viral progeny. Levels of HSP27 induction were viral dose-dependent and were not accompanied by any alterations in cellular proliferation. In contrast, acute HIV-infection was not associated with significant quantitative changes in the constitutive expression of HSP60, HSP70, or HSP90. Nevertheless, a transient, marked induction of select HSP70 subspecies was evident at early stages of infection, finally disappearing by 48-72h. Acute-infection of Jurkat cells resulted in similar patterns of de novo induction of HSP27 and HSP70 isoforms. Uninfected and chronically-infected CEM extracts showed little detectable constitutive HSP27. However, synthesis of select HSP27 and HSP70 homologues in chronically-infected cells was observed following exposure to a mild heat shock and doses of TNF$ alpha$. Similar HSP70 homologues arose in chronically-infected cells treated with heat-shock and TNF$ alpha$. These findings indicate that HSP pathways are uniquely modulated in CD4+ cells as a consequence of acute and chronic HIV-1 infection.

Identiferoai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.27432
Date January 1996
CreatorsWainberg, Zev.
ContributorsBrenner, Bluma (advisor)
PublisherMcGill University
Source SetsLibrary and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada
LanguageEnglish
Detected LanguageEnglish
TypeElectronic Thesis or Dissertation
Formatapplication/pdf
CoverageMaster of Science (Division of Surgical Research.)
RightsAll items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated.
Relationalephsysno: 001548741, proquestno: MQ29807, Theses scanned by UMI/ProQuest.

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