NuMA and nuclear lamins are cleaved during viral infection--inhibition of caspase activity prevents cleavage and rescues HeLa cells from measles virus-induced but not from rhinovirus 1B-induced cell death.
Nuclear matrix is a structural framework of important nuclear processes. We studied the effect of two different types of viral infections on nuclear matrix. HeLa cells were infected with human rhinovirus 1B (HRV 1B) or measles virus (MV), and Nuclear Mitotic Apparatus protein (NuMA) and lamins A/C and B were used as markers for internal nuclear matrix and peripheral nuclear lamina, respectively. We show that NuMA, lamins, and poly(ADP-ribose) polymerase-1 are cleaved during viral infection in a virus family-specific manner suggesting that these viruses activate different sets of proteases. Morphologically, NuMA was excluded from the condensed chromatin, lamins showed a folded distribution, and both proteins finally remained around the nuclear fragments. A general caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (z-VAD-FMK) prevented the nuclear disintegration and the cleavage of the proteins studied. Interestingly, z-VAD-FMK rescued MV-infected but not HRV 1B-infected cells from cell death. These results show for the first time that NuMA and lamins are specific target proteins during virus-induced programmed cell death.
Taimen
Pekka
P
Department of Pathology, University of Turku, Kiinamyllynkatu 10, FIN-20520 Turku, Finland. pekka.taimen@utu.fi
Berghäll
Heidi
H
Vainionpää
Raija
R
Kallajoki
Markku
M
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D034961:Antigens, Nuclear; D061945:Caspase Inhibitors; D018797:Cell Cycle Proteins; D016923:Cell Death / Q000187:drug effects; D002467:Cell Nucleus / Q000378:metabolism; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D034882:Lamins / Q000378:metabolism*; D008459:Measles virus; D034881:Nuclear Lamina / Q000378:metabolism* / Q000821:virology; D034521:Nuclear Matrix-Associated Proteins; D009687:Nuclear Proteins / Q000378:metabolism*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D012229:Rhinovirus; D013045:Species Specificity; D008941:Spindle Apparatus / Q000378:metabolism*
D000590:Amino Acid Chloromethyl Ketones; D034961:Antigens, Nuclear; D061945:Caspase Inhibitors; D018797:Cell Cycle Proteins; D015853:Cysteine Proteinase Inhibitors; D034882:Lamins; C050045:NUMA1 protein, human; D034521:Nuclear Matrix-Associated Proteins; D009687:Nuclear Proteins; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D011065:Poly(ADP-ribose) Polymerases