HIV infection in vitro enhances the activity of src-family protein tyrosine kinases

David J. Phipps, Stanley E. Read, John P. Piovesan, Gordon Mills, Donald R. Branch

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Objective: We examined the effect of HIV infection on src-family protein tyrosine kinase (PTK) activity to determine if alterations in src-family PTK activity could contribute to the HIV-related chronic immune System activation observed in patients infected with HIV. Methods: Jurkat, a CD4+ human T lymphocyte cell line was infected with HIV III(B). Kinase activity was determined by in vitro immune complex kinase assays using antibodies specific for the src-family PTKs, p56(lck), p59(fyn) and p60(c-src) expressed in T lymphocytes. PTK protein and total phosphotyrosine levels were assessed by Western blotting. The role of the gp120-CD4-Lck interaction in HIV-related PTK activation was determined using gp120-treated Jurkat cells and HIV-infection of jCaM 1.6 cells, a Jurkat-derived cell line that lacks p56(lck). Results: Cells infected with HIV for 24 h exhibited increased levels of total tyrosine phosphorylation and enhanced src-family PTK activity without altered levels of expression of src-family kinases. The activity of Lck and Fyn was enhanced within 30 min of infection. HIV-related src-family PTK activation was not a function of the gp120-CD4-Lck interaction and occurred in the presence of 10 mmol/l zidovudine indicating that reverse transcriptase and activation of the HIV genome is not required. Conclusions: HIV-related activation of src-family PTK is a response of the cell to early stages of the virus life cycle, possibly either membrane fusion or viral uncoating. These results indicate that endogenous src-family PTKs may play a role in HIV-related immune activation and dysfunction. Moreover, activation of src-family PTK may be a mechanism used by the virus to facilitate some aspect of its own life cycle.

Original languageEnglish (US)
Pages (from-to)1191-1198
Number of pages8
JournalAIDS
Volume10
Issue number11
DOIs
StatePublished - Jan 1 1996
Externally publishedYes

Fingerprint

src-Family Kinases
HIV Infections
HIV
Jurkat Cells
Life Cycle Stages
In Vitro Techniques
Protein-Tyrosine Kinases
Virus Uncoating
Phosphotransferases
Viruses
Human Immunodeficiency Virus Proteins
T-Lymphocytes
HIV Reverse Transcriptase
Cell Line
Phosphotyrosine
Membrane Fusion
Zidovudine
Antigen-Antibody Complex
Tyrosine
Immune System

Keywords

  • Fyn
  • gp120
  • HIV
  • Lck
  • Protein tyrosine kinase
  • Signal transduction
  • src
  • Src kinases

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

HIV infection in vitro enhances the activity of src-family protein tyrosine kinases. / Phipps, David J.; Read, Stanley E.; Piovesan, John P.; Mills, Gordon; Branch, Donald R.

In: AIDS, Vol. 10, No. 11, 01.01.1996, p. 1191-1198.

Research output: Contribution to journalArticle

Phipps, David J. ; Read, Stanley E. ; Piovesan, John P. ; Mills, Gordon ; Branch, Donald R. / HIV infection in vitro enhances the activity of src-family protein tyrosine kinases. In: AIDS. 1996 ; Vol. 10, No. 11. pp. 1191-1198.
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abstract = "Objective: We examined the effect of HIV infection on src-family protein tyrosine kinase (PTK) activity to determine if alterations in src-family PTK activity could contribute to the HIV-related chronic immune System activation observed in patients infected with HIV. Methods: Jurkat, a CD4+ human T lymphocyte cell line was infected with HIV III(B). Kinase activity was determined by in vitro immune complex kinase assays using antibodies specific for the src-family PTKs, p56(lck), p59(fyn) and p60(c-src) expressed in T lymphocytes. PTK protein and total phosphotyrosine levels were assessed by Western blotting. The role of the gp120-CD4-Lck interaction in HIV-related PTK activation was determined using gp120-treated Jurkat cells and HIV-infection of jCaM 1.6 cells, a Jurkat-derived cell line that lacks p56(lck). Results: Cells infected with HIV for 24 h exhibited increased levels of total tyrosine phosphorylation and enhanced src-family PTK activity without altered levels of expression of src-family kinases. The activity of Lck and Fyn was enhanced within 30 min of infection. HIV-related src-family PTK activation was not a function of the gp120-CD4-Lck interaction and occurred in the presence of 10 mmol/l zidovudine indicating that reverse transcriptase and activation of the HIV genome is not required. Conclusions: HIV-related activation of src-family PTK is a response of the cell to early stages of the virus life cycle, possibly either membrane fusion or viral uncoating. These results indicate that endogenous src-family PTKs may play a role in HIV-related immune activation and dysfunction. Moreover, activation of src-family PTK may be a mechanism used by the virus to facilitate some aspect of its own life cycle.",
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AB - Objective: We examined the effect of HIV infection on src-family protein tyrosine kinase (PTK) activity to determine if alterations in src-family PTK activity could contribute to the HIV-related chronic immune System activation observed in patients infected with HIV. Methods: Jurkat, a CD4+ human T lymphocyte cell line was infected with HIV III(B). Kinase activity was determined by in vitro immune complex kinase assays using antibodies specific for the src-family PTKs, p56(lck), p59(fyn) and p60(c-src) expressed in T lymphocytes. PTK protein and total phosphotyrosine levels were assessed by Western blotting. The role of the gp120-CD4-Lck interaction in HIV-related PTK activation was determined using gp120-treated Jurkat cells and HIV-infection of jCaM 1.6 cells, a Jurkat-derived cell line that lacks p56(lck). Results: Cells infected with HIV for 24 h exhibited increased levels of total tyrosine phosphorylation and enhanced src-family PTK activity without altered levels of expression of src-family kinases. The activity of Lck and Fyn was enhanced within 30 min of infection. HIV-related src-family PTK activation was not a function of the gp120-CD4-Lck interaction and occurred in the presence of 10 mmol/l zidovudine indicating that reverse transcriptase and activation of the HIV genome is not required. Conclusions: HIV-related activation of src-family PTK is a response of the cell to early stages of the virus life cycle, possibly either membrane fusion or viral uncoating. These results indicate that endogenous src-family PTKs may play a role in HIV-related immune activation and dysfunction. Moreover, activation of src-family PTK may be a mechanism used by the virus to facilitate some aspect of its own life cycle.

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