HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Evidence for a pathogenic determinant in HIV-1 Nef involved in B cell dysfunction in HIV/AIDS.

Abstract
B lymphocyte hyperactivation and elevated immunoglobulin levels (hypergammaglobulinemia) are pathogenic manifestations of HIV-1 infection. Here we provide evidence that these hallmarks are caused by a soluble factor whose production by infected macrophages is induced by the HIV-1 Nef protein. In vitro, HIV-1-infected macrophages or macrophages expressing Nef promoted B cell activation and differentiation to immunoglobulin-secreting cells. Nef-mediated activation of NF-kappaB in macrophages induced secretion of the acute-phase protein ferritin, and ferritin was necessary and sufficient for the observed Nef-dependent B cell changes. The extent of hypergammaglobulinemia in HIV-1-infected individuals correlated directly with plasma ferritin levels and with viral load. Furthermore, the induction of ferritin production and hypergammaglobulinemia was recapitulated when Nef was specifically expressed in macrophages and T cells of transgenic mice. Collectively, these results indicate that the HIV-1 Nef protein carries a pathogenic determinant that governs B cell defects in HIV-1 infection.
AuthorsSimon Swingler, Jin Zhou, Catherine Swingler, Ann Dauphin, Thomas Greenough, Paul Jolicoeur, Mario Stevenson
JournalCell host & microbe (Cell Host Microbe) Vol. 4 Issue 1 Pg. 63-76 (Jul 17 2008) ISSN: 1934-6069 [Electronic] United States
PMID18621011 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • NF-kappa B
  • Virulence Factors
  • nef Gene Products, Human Immunodeficiency Virus
  • nef protein, Human immunodeficiency virus 1
  • Ferritins
Topics
  • Animals
  • B-Lymphocytes (immunology)
  • Ferritins (blood, metabolism)
  • HIV-1 (genetics, pathogenicity)
  • Humans
  • Hypergammaglobulinemia
  • Lymphocyte Activation
  • Macrophages (virology)
  • Mice
  • Mice, Transgenic
  • NF-kappa B (metabolism)
  • Statistics as Topic
  • Viral Load
  • Virulence Factors (genetics, physiology)
  • nef Gene Products, Human Immunodeficiency Virus (genetics, physiology)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: