E1B and E4 oncoproteins of adenovirus antagonize the effect of apoptosis inducing factor.

Abstract:

:Adenovirus inundates the productively infected cell with linear, double-stranded DNA and an abundance of single-stranded DNA. The cellular response to this stimulus is antagonized by the adenoviral E1B and E4 early genes. A mutant group C adenovirus that fails to express the E1B-55K and E4orf3 genes is unable to suppress the DNA-damage response. Cells infected with this double-mutant virus display significant morphological heterogeneity at late times of infection and frequently contain fragmented nuclei. Nuclear fragmentation was due to the translocation of apoptosis inducing factor (AIF) from the mitochondria into the nucleus. The release of AIF was dependent on active poly(ADP-ribose) polymerase-1 (PARP-1), which appeared to be activated by viral DNA replication. Nuclear fragmentation did not occur in AIF-deficient cells or in cells treated with a PARP-1 inhibitor. The E1B-55K or E4orf3 proteins independently prevented nuclear fragmentation subsequent to PARP-1 activation, possibly by altering the intracellular distribution of PAR-modified proteins.

journal_name

Virology

journal_title

Virology

authors

Turner RL,Wilkinson JC,Ornelles DA

doi

10.1016/j.virol.2014.03.010

subject

Has Abstract

pub_date

2014-05-01 00:00:00

pages

205-19

eissn

0042-6822

issn

1096-0341

pii

S0042-6822(14)00092-0

journal_volume

456-457

pub_type

杂志文章

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