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PMID: 9032389 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Molecular determinants for cellular uptake of Tat protein of human immunodeficiency virus type 1 in brain cells.

Journal of virology ·Vol. 71 ·No. 3 ·1997-03-00 ·Pages 2495-9

Ma M, Nath A

Abstract

We measured the cellular uptake of 125I-labeled full-length Tat (amino acids 1 to 86) (125I-Tat(1-86)) and 125I-Tat(1-72) (first exon) in human fetal astrocytes, neuroblastoma cells, and human fetal neurons and demonstrated that the uptake of 125I-Tat(1-72) without the second exon was much lower than that of 125I-Tat(1-86) (P < 0.01). This suggests an important role for the C-terminal region of Tat for its cellular uptake. 125I-Tat uptake could be inhibited by dextran sulfate and competitively inhibited by unlabeled Tat but not by overlapping 15-mer peptides, suggesting that Tat internalization is charge and conformationally dependent. Interestingly, one of 15-mer peptides, Tat(28-42), greatly enhanced 125I-Tat uptake. These findings are important for understanding the neuropathogenesis of human immunodeficiency virus type 1 infection and in the potential application of Tat for drug delivery to cells.

MeSH Terms
Amino Acid Sequence Astrocytes/cytology,metabolism Brain/cytology,embryology,metabolism Cell Line Dextran Sulfate/pharmacology Gene Products, tat/pharmacokinetics HIV-1/metabolism Humans Integrins/metabolism Molecular Sequence Data Neurons/cytology,metabolism Tumor Cells, Cultured tat Gene Products, Human Immunodeficiency Virus
Chemicals
Gene Products, tat Integrins tat Gene Products, Human Immunodeficiency Virus Dextran Sulfate
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Ma M
Department of Medical Microbiology, University of Manitoba, Winnipeg, Canada.
Nath A
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32 references, click to expand
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.71.3.2495-2499.1997
Published
1997-03-00
Pages
2495-9
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC191362
Subset
IM
External Links
PubMed source DOI: 10.1128/JVI.71.3.2495-2499.1997 PMC Full Text View journal details
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