Vesicular stomatitis virus inhibits mitotic progression and triggers cell death.
Vesicular stomatitis virus (VSV) infects and kills a wide range of cell types; however, the mechanisms involved in VSV-mediated cell death are not fully understood. Here we show that VSV infection interferes with mitotic progression, resulting in cell death. This effect requires the interaction of VSV matrix (M) protein with the Rae1-Nup98 complex in mitosis, which is associated with a subset of ribonucleoproteins (RNPs). VSV displaced Rae1 from spindle poles, caused spindle abnormalities and triggered substantial cell death during metaphase. These effects were attenuated in cells infected with VSV expressing a mutant M protein that does not bind efficiently to the Rae1-Nup98-RNP complex. In cells that progressed to late mitosis, M protein prevented proper nuclear formation and chromatin decondensation. VSV is an oncolytic (anti-tumour) agent as it preferentially replicates and kills tumour cells. As tumour cells have a high mitotic index, VSV-mediated mitotic cell death probably contributes to its oncolytic activity.
Chakraborty
Papia
P
Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Seemann
Joachim
J
Mishra
Ram K
RK
Wei
Jen-Hsuan
JH
Weil
Lauren
L
Nussenzveig
Daniel R
DR
Heiber
Joshua
J
Barber
Glen N
GN
Dasso
Mary
M
Fontoura
Beatriz M A
BM
D000818:Animals; D016923:Cell Death; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D006801:Humans; D008938:Mitosis; D034521:Nuclear Matrix-Associated Proteins / Q000378:metabolism; D028861:Nuclear Pore Complex Proteins / Q000378:metabolism; D029543:Nucleocytoplasmic Transport Proteins / Q000378:metabolism; D009865:Oocytes / Q000378:metabolism; D011485:Protein Binding; D051381:Rats; D012261:Ribonucleoproteins / Q000378:metabolism; D018116:Vesiculovirus / Q000502:physiology*; D014763:Viral Matrix Proteins / Q000378:metabolism; D014981:Xenopus
C094460:M protein, Vesicular stomatitis virus; D034521:Nuclear Matrix-Associated Proteins; D028861:Nuclear Pore Complex Proteins; D029543:Nucleocytoplasmic Transport Proteins; C465451:Nup98 protein, human; C490522:RAE1 protein, human; D012261:Ribonucleoproteins; D014763:Viral Matrix Proteins