The Long Cytoplasmic Tail of gp41 Is Required in a Cell Type-Dependent Manner for HIV-1 Envelope Glycoprotein Incorporation into Virions

Lentiviruses, including HIV-1, have transmembrane envelope (Env) glycoproteins with cytoplasmic tails that are quite long compared with those of other retroviruses. However, mainly because of the lack of biochemical studies performed in cell types that are targets for HIV-1 infection, no clear conse...

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Veröffentlicht in:Proceedings of the National Academy of Sciences - PNAS 2000-01, Vol.97 (1), p.343-348
Hauptverfasser: Murakami, Tsutomu, Freed, Eric O.
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description Lentiviruses, including HIV-1, have transmembrane envelope (Env) glycoproteins with cytoplasmic tails that are quite long compared with those of other retroviruses. However, mainly because of the lack of biochemical studies performed in cell types that are targets for HIV-1 infection, no clear consensus exists regarding the function of the long lentiviral Env cytoplasmic tail in virus replication. In this report, we characterize the biological and biochemical properties of an HIV-1 mutant lacking the gp41 cytoplasmic tail. We find that the gp41 cytoplasmic tail is necessary for the efficient establishment of a productive, spreading infection in the majority of T cell lines tested, peripheral blood mononuclear cells, and monocyte-derived macrophages. Biochemical studies using a high-level, transient HIV-1 expression system based on pseudotyping with the vesicular stomatitis virus glycoprotein demonstrate that in HeLa and MT-4 cells, mutant Env incorporation into virions is reduced only 3-fold relative to wild type. In contrast, gp120 levels in virions produced from a number of other T cell lines and primary macrophages are reduced more than 10-fold by the gp41 truncation. The Env incorporation defect imposed by the cytoplasmic tail truncation is not the result of increased shedding of gp120 from virions or reduced cell-surface Env expression. These results demonstrate that in the majority of T cell lines, and in primary cell types that serve as natural targets for HIV-1 infection in vivo, the gp41 cytoplasmic tail is essential for efficient Env incorporation into virions.
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subjects AIDS/HIV
Biological Sciences
Cell Line
Cell lines
cytoplasmic tail
env protein
Epithelial cells
Gene Expression Regulation, Viral
glycoprotein gp41
Glycoproteins
HeLa cells
HIV
HIV 1
HIV Envelope Protein gp120 - metabolism
HIV-1 - genetics
HIV-1 - metabolism
Human immunodeficiency virus
Human immunodeficiency virus 1
Humans
Infections
Kinetics
Lentivirus
Membrane Glycoproteins - genetics
Membrane Glycoproteins - metabolism
Mutation
Precipitin Tests
Proteins
T lymphocytes
T-Lymphocytes - virology
Transfection
Truncation
Virions
Virus Replication - genetics
Viruses
title The Long Cytoplasmic Tail of gp41 Is Required in a Cell Type-Dependent Manner for HIV-1 Envelope Glycoprotein Incorporation into Virions
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