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PMID: 2201025 Published · ppublish English Journal Article

Human immunodeficiency virus type 1 protease cleaves the intermediate filament proteins vimentin, desmin, and glial fibrillary acidic protein.

Shoeman RL, Höner B, Stoller TJ, Kesselmeier C, Miedel MC, Traub P, Graves MC

Abstract

The intermediate filament proteins vimentin, desmin, and glial fibrillary acidic protein are cleaved in vitro by human immunodeficiency virus type 1 protease (HIV-1 PR). Microsequencing showed that HIV-1 PR cleaved both human and murine vimentin between leucine-422 and arginine-423 within the sequence between positions 418 and 427, Ser-Ser-Leu-Asn-Leu/Arg-Glu-Thr-Asn-Leu (SSLNL/RETNL). Minor cleavages at other sites were also observed. Heat-denatured vimentin was cleaved by HIV-1 PR less efficiently than native vimentin. A decapeptide containing the sequence SSLN-LRETNL was also cleaved in vitro by HIV-1 PR as predicted. The presence of a charged residue (arginine) at the primary cleavage site distinguishes this from other known naturally occurring cleavage sites. Microinjection of HIV-1 PR into cultured human fibroblasts resulted in a 9-fold increase in the percentage of cells with an altered and abnormal distribution of vimentin intermediate filaments. Most commonly, the intermediate filaments collapsed into a clump with a juxtanuclear localization. These results support the possibility that intermediate filament proteins may serve as substrates within HIV-1-infected cells.

MeSH Terms
Amino Acid Sequence Animals Carcinoma, Ehrlich Tumor Desmin/metabolism Endopeptidases/metabolism Gene Products, pol/metabolism Glial Fibrillary Acidic Protein/metabolism HIV Protease HIV-1/enzymology HeLa Cells Humans Intermediate Filament Proteins/metabolism Mice Molecular Sequence Data Oligopeptides/chemical synthesis,metabolism Recombinant Proteins/metabolism Substrate Specificity Vimentin/metabolism
Chemicals
Desmin Gene Products, pol Glial Fibrillary Acidic Protein Intermediate Filament Proteins Oligopeptides Recombinant Proteins Vimentin Endopeptidases HIV Protease
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Shoeman R L
Max-Planck-Institut für Zellbiologie, Abteilung Traub, Rosenhof, Federal Republic of Germany.
Höner B
Stoller T J
Kesselmeier C
Miedel M C
Traub P
Graves M C
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
Published
1990-08-00
Pages
6336-40
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC54528
Subset
IM
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