Cleavage of human and mouse cytoskeletal and sarcomeric proteins by human immunodeficiency virus type 1 protease. Actin, desmin, myosin, and tropomyosin.
HeLa cell actin was cleaved by human immunodeficiency virus type 1 protease when in its soluble, globular form (G-actin). No cleavage of the polymerized, filamentous form of actin (F-actin) was observed when examined by denaturing gel electrophoresis; however, electron microscopy revealed a low level of cleavage of F-actin. Immunoblotting of mouse skeletal and human pectoral muscle myofibrils treated in vitro with human immunodeficiency virus type 1 protease showed that myosin heavy chain, desmin, tropomyosin, and a fraction of the actin were all cleaved. Electron microscopy of these myofibrils demonstrated changes consistent with cleavage of these proteins: Z-lines were rapidly lost, the length of the A bands was shortened, and the thick filaments (myosin filaments) were often laterally frayed such that the structures disintegrated. Nonmuscle myosin heavy chains were also cleaved by this enzyme in vitro. These data demonstrate that this protease can cause alterations in muscle cell ultrastructure in vitro that may be of clinical relevance in infected individuals.
Shoeman
R L
RL
Max-Planck-Institut für Zellbiologie, Ladenburg, Federal Republic of Germany.
Sachse
C
C
Höner
B
B
Mothes
E
E
Kaufmann
M
M
Traub
P
P
D000199:Actins / Q000187:drug effects / Q000648:ultrastructure; D000818:Animals; D003893:Desmin / Q000187:drug effects* / Q000648:ultrastructure; D016333:HIV Protease / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008840:Microfilament Proteins / Q000187:drug effects* / Q000648:ultrastructure; D009218:Myosins / Q000187:drug effects / Q000648:ultrastructure; D012518:Sarcomeres / Q000737:chemistry / Q000187:drug effects*; D014335:Tropomyosin / Q000187:drug effects / Q000648:ultrastructure; D014764:Viral Proteins / Q000494:pharmacology*
D000199:Actins; D003893:Desmin; D008840:Microfilament Proteins; D014335:Tropomyosin; D014764:Viral Proteins; D016333:HIV Protease; D009218:Myosins