An antiviral disulfide compound blocks interaction between arenavirus Z protein and cellular promyelocytic leukemia protein

Journal Article · Fri Mar 19 04:00:00 EDT 2010 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2010.02.040· OSTI ID:22202415

Garcia, C. C. ^[1]; Topisirovic, I. ^[2]; Djavani, M. ^[3]; Borden, K. L.B. ^[2]; Damonte, E. B. ^[1]

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1. Laboratory of Virology, Department of Biological Chemistry, School of Sciences, University of Buenos Aires, 1428 Buenos Aires (Argentina)
2. Institute de Recherche en Immunologie et en Cancerologie, Universite de Montreal, Montreal, QC, Canada H3T 1J4 (Canada)
3. Institute of Human Virology, School of Medicine, University of Maryland, Baltimore, MD 21201 (United States)

The promyelocytic leukemia protein (PML) forms nuclear bodies (NB) that can be redistributed by virus infection. In particular, lymphocytic choriomeningitis virus (LCMV) influences disruption of PML NB through the interaction of PML with the arenaviral Z protein. In a previous report, we have shown that the disulfide compound NSC20625 has antiviral and virucidal properties against arenaviruses, inducing unfolding and oligomerization of Z without affecting cellular RING-containing proteins such as the PML. Here, we further studied the effect of the zinc-finger-reactive disulfide NSC20625 on PML-Z interaction. In HepG2 cells infected with LCMV or transiently transfected with Z protein constructs, treatment with NSC20625 restored PML distribution from a diffuse-cytoplasmic pattern to punctate, discrete NB which appeared identical to NB found in control, uninfected cells. Similar results were obtained in cells transfected with a construct expressing a Z mutant in zinc-binding site 2 of the RING domain, confirming that this Z-PML interaction requires the integrity of only one zinc-binding site. Altogether, these results show that the compound NSC20625 suppressed Z-mediated PML NB disruption and may be used as a tool for designing novel antiviral strategies against arenavirus infection.

• OSTI ID: 22202415
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 4 Vol. 393; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
BROMIDES
CYANOGEN
DISULFIDES
DNA
FLUORESCEIN
LEUKEMIA
LEUKEMIA VIRUSES
MICROSCOPY
MONOCLONAL ANTIBODIES
MUTANTS
TETRAZOLIUM