Cellular uptake of the tat protein from human immunodeficiency virus.
While developing an assay to measure the activity of the tat protein from human immunodeficiency virus 1 (HIV-1), we discovered that the purified protein could be taken up by cells growing in tissue culture and subsequently trans-activate the viral promoter. Trans-activation is dramatically increased by a variety of lysosomotrophic agents. For example, trans-activation can be detected at tat concentrations as low as 1 nM in the presence of chloroquine. Experiments using radioactive protein show that tat becomes localized to the nucleus after uptake and suggest that chloroquine protects tat from proteolytic degradation. These results raise the possibility that, under some conditions, tat might act as a viral growth factor to stimulate viral replication in latently infected cells or alter expression of cellular genes.
Frankel
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Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Pabo
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D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D002738:Chloroquine / Q000494:pharmacology; D005786:Gene Expression Regulation; D015696:Gene Products, tat; D006678:HIV / Q000235:genetics / Q000378:metabolism*; D010957:Plasmids; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000493:pharmacokinetics*; D014162:Transfection; D054322:tat Gene Products, Human Immunodeficiency Virus
D015696:Gene Products, tat; D014157:Transcription Factors; D054322:tat Gene Products, Human Immunodeficiency Virus; D002738:Chloroquine