Human immunodeficiency virus induces phosphorylation of its cell surface receptor

Alan P Fields, Daniel P. Bednarik, Allan Hess, W. Stratford May

Research output: Contribution to journalArticle

108 Citations (Scopus)

Abstract

AIDS is an immunoregulatory disorder characterized by depletion of the CD4+, helper/inducer lymphocyte population1. The causative agent of this disease is the human immunodeficiency virus, HIV2-4, which infects CD4+ cells and leads to cytopathic effects characterized by syncytia formation and cell death5,6. Recent studies have demonstrated that binding of HIV to its cellular receptor CD4 is necessary for viral entry7,8. We find that binding of HIV to CD4 induces rapid and sustained phosphorylation of CD4 which could involve protein kinase C. HIV-induced CD4 phosphorylation can be blocked by antibody against CD4 and monoclonal antibody against the HIV envelope glycoprotein gp120, indicating that a specific interaction between CD4 and gp120 is required for phosphorylation. Electron microscopy shows that a protein kinase C inhibitor does not impair binding of HIV to CD4+ cells, but causes an apparent accumulation of virus particles at the cell surface, at the same time inhibiting viral infectivity. These results indicate a possible role for HIV-induced CD4 phosphorylation in viral entry and identify a potential target for antiviral therapy.

Original languageEnglish (US)
Pages (from-to)278-280
Number of pages3
JournalNature
Volume333
Issue number6170
StatePublished - 1988
Externally publishedYes

Fingerprint

Cell Surface Receptors
Phosphorylation
HIV
Protein Kinase C
HIV Envelope Protein gp120
CD4 Antigens
Protein C Inhibitor
Giant Cells
Protein Kinase Inhibitors
Virion
Antiviral Agents
Electron Microscopy
Acquired Immunodeficiency Syndrome
Monoclonal Antibodies
Lymphocytes
Antibodies

ASJC Scopus subject areas

  • General

Cite this

Fields, A. P., Bednarik, D. P., Hess, A., & Stratford May, W. (1988). Human immunodeficiency virus induces phosphorylation of its cell surface receptor. Nature, 333(6170), 278-280.

Human immunodeficiency virus induces phosphorylation of its cell surface receptor. / Fields, Alan P; Bednarik, Daniel P.; Hess, Allan; Stratford May, W.

In: Nature, Vol. 333, No. 6170, 1988, p. 278-280.

Research output: Contribution to journalArticle

Fields, AP, Bednarik, DP, Hess, A & Stratford May, W 1988, 'Human immunodeficiency virus induces phosphorylation of its cell surface receptor', Nature, vol. 333, no. 6170, pp. 278-280.
Fields AP, Bednarik DP, Hess A, Stratford May W. Human immunodeficiency virus induces phosphorylation of its cell surface receptor. Nature. 1988;333(6170):278-280.
Fields, Alan P ; Bednarik, Daniel P. ; Hess, Allan ; Stratford May, W. / Human immunodeficiency virus induces phosphorylation of its cell surface receptor. In: Nature. 1988 ; Vol. 333, No. 6170. pp. 278-280.
@article{24b7f09b1f4f41a193672d64b6f90cff,
title = "Human immunodeficiency virus induces phosphorylation of its cell surface receptor",
abstract = "AIDS is an immunoregulatory disorder characterized by depletion of the CD4+, helper/inducer lymphocyte population1. The causative agent of this disease is the human immunodeficiency virus, HIV2-4, which infects CD4+ cells and leads to cytopathic effects characterized by syncytia formation and cell death5,6. Recent studies have demonstrated that binding of HIV to its cellular receptor CD4 is necessary for viral entry7,8. We find that binding of HIV to CD4 induces rapid and sustained phosphorylation of CD4 which could involve protein kinase C. HIV-induced CD4 phosphorylation can be blocked by antibody against CD4 and monoclonal antibody against the HIV envelope glycoprotein gp120, indicating that a specific interaction between CD4 and gp120 is required for phosphorylation. Electron microscopy shows that a protein kinase C inhibitor does not impair binding of HIV to CD4+ cells, but causes an apparent accumulation of virus particles at the cell surface, at the same time inhibiting viral infectivity. These results indicate a possible role for HIV-induced CD4 phosphorylation in viral entry and identify a potential target for antiviral therapy.",
author = "Fields, {Alan P} and Bednarik, {Daniel P.} and Allan Hess and {Stratford May}, W.",
year = "1988",
language = "English (US)",
volume = "333",
pages = "278--280",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "6170",

}

TY - JOUR

T1 - Human immunodeficiency virus induces phosphorylation of its cell surface receptor

AU - Fields, Alan P

AU - Bednarik, Daniel P.

AU - Hess, Allan

AU - Stratford May, W.

PY - 1988

Y1 - 1988

N2 - AIDS is an immunoregulatory disorder characterized by depletion of the CD4+, helper/inducer lymphocyte population1. The causative agent of this disease is the human immunodeficiency virus, HIV2-4, which infects CD4+ cells and leads to cytopathic effects characterized by syncytia formation and cell death5,6. Recent studies have demonstrated that binding of HIV to its cellular receptor CD4 is necessary for viral entry7,8. We find that binding of HIV to CD4 induces rapid and sustained phosphorylation of CD4 which could involve protein kinase C. HIV-induced CD4 phosphorylation can be blocked by antibody against CD4 and monoclonal antibody against the HIV envelope glycoprotein gp120, indicating that a specific interaction between CD4 and gp120 is required for phosphorylation. Electron microscopy shows that a protein kinase C inhibitor does not impair binding of HIV to CD4+ cells, but causes an apparent accumulation of virus particles at the cell surface, at the same time inhibiting viral infectivity. These results indicate a possible role for HIV-induced CD4 phosphorylation in viral entry and identify a potential target for antiviral therapy.

AB - AIDS is an immunoregulatory disorder characterized by depletion of the CD4+, helper/inducer lymphocyte population1. The causative agent of this disease is the human immunodeficiency virus, HIV2-4, which infects CD4+ cells and leads to cytopathic effects characterized by syncytia formation and cell death5,6. Recent studies have demonstrated that binding of HIV to its cellular receptor CD4 is necessary for viral entry7,8. We find that binding of HIV to CD4 induces rapid and sustained phosphorylation of CD4 which could involve protein kinase C. HIV-induced CD4 phosphorylation can be blocked by antibody against CD4 and monoclonal antibody against the HIV envelope glycoprotein gp120, indicating that a specific interaction between CD4 and gp120 is required for phosphorylation. Electron microscopy shows that a protein kinase C inhibitor does not impair binding of HIV to CD4+ cells, but causes an apparent accumulation of virus particles at the cell surface, at the same time inhibiting viral infectivity. These results indicate a possible role for HIV-induced CD4 phosphorylation in viral entry and identify a potential target for antiviral therapy.

UR - http://www.scopus.com/inward/record.url?scp=0023922690&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0023922690&partnerID=8YFLogxK

M3 - Article

C2 - 3259291

AN - SCOPUS:0023922690

VL - 333

SP - 278

EP - 280

JO - Nature

JF - Nature

SN - 0028-0836

IS - 6170

ER -