The Src kinase Lck facilitates assembly of HIV-1 at the plasma membrane

Amy B. Strasner, Malini Natarajan, Tom Doman, Douglas Key, Avery August, Andrew J. Henderson

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Abstract

HIV type 1 (HIV-1) assembly and egress are driven by the viral protein Gag and occur at the plasma membrane in T cells. Recent evidence indicates that secretory vesicles and machinery are essential components of virus packaging in both T cells and macrophages. However, the pathways and cellular mediators of Gag targeting to the plasma membrane are not well characterized. Lck, a lymphoid specific Src kinase critical for T cell activation, is found in the plasma membrane as well as various intracellular compartments and it has been suggested to influence HIV-1 replication. To investigate Lck as a potential regulator of Gag targeting, we assessed HIV-1 replication and Gag-induced virus-like particle release in the presence and absence of Lck. Release of HIV-1 and virus-like particles was reduced in the absence of Lck. This decrease in replication was not due to altered HIV-1 infection, transcription or protein translation. However, in T cells lacking Lck, HIV-1 accumulated intracellularly. In addition, expressing Lck in HeLa cells promoted HIV-1 Gag plasma membrane localization. Palmitoylation of the Lck unique domain, which is essential for directing Lck to the plasma membrane, was critical for its effect on HIV-1 replication. Furthermore, HIV-1 Gag directly interacted with the Lck unique domain in the context of infected cells. These results indicate that Lck plays a key role in targeting HIV-1 Gag to the plasma membrane in T cells.

Original languageEnglish (US)
Pages (from-to)3706-3713
Number of pages8
JournalJournal of Immunology
Volume181
Issue number5
DOIs
StatePublished - Sep 1 2008

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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    Strasner, A. B., Natarajan, M., Doman, T., Key, D., August, A., & Henderson, A. J. (2008). The Src kinase Lck facilitates assembly of HIV-1 at the plasma membrane. Journal of Immunology, 181(5), 3706-3713. https://doi.org/10.4049/jimmunol.181.5.3706