DNA damage response confers a barrier for viral tumorigenesis

September 28, 2007

Kaposi’s sarcoma herpesvirus (KSHV) is a human tumor virus and an etiological agent for Kaposi’s sarcoma (KS). KSHV infection is endemic in sub-Saharan Africa where KS is nowadays the most common malignancy, due to widespread infection with KSHV and human immunodeficiency virus (HIV). Importantly, KS also occurs in HIV-negative individuals. Researchers at the University of Helsinki, Finland, have discovered that activation of the DNA damage response in the early stages of KS development functions as an anti-cancer barrier also in virus induced malignancies.

Recent findings suggest that DNA damage checkpoints become activated in early stages of human tumorigenesis, leading to growth arrest or apoptosis and thereby hindering tumor progression. DNA hyper-replication triggered by oncogenes can induce cellular senescence, which together with the oncogene-induced DNA damage checkpoint function as an early anti-cancer barrier. The findings by the research group of Päivi Ojala, Ph.D., (University of Helsinki) demonstrate that the DNA damage checkpoint is activated during the initial stages of KSHV infection and KS tumorigenesis and this can confer a barrier to tumorigenesis also in virus induced cancers.

The study will be published 28.9.2007 in Public Library of Science (PLoS) Pathogens.

KSHV displays two patterns of infection: latent and lytic phase. During latency, only a restricted set of viral genes is expressed. The KSHV genome encodes several homologues of cellular proteins, which engage cellular signaling pathways, govern cell proliferation and modulate apoptosis. The results of this study demonstrate that one of the viral latent proteins, viral cyclin, which is a homolog of cellular D-type cyclins, induces replicative stress in endothelial cells, which leads to senescence and activation of the DNA damage response.

To support the finding early stage lesions of clinical KS specimens were analysed in the study. The results demonstrate that DNA damage checkpoint is activated in early, but not late stage lesions of clinical KS specimens. During the course of infection, the KSHV infected cells may be imposed to overcome this checkpoint, and oncogenic stress elicited by the expression of the viral cyclin may further contribute to the induction of genomic instability and malignant transformation.

Source: University of Helsinki

Explore further: Stress wakes up sleeping herpes viruses – but how?

Related Stories

Stress wakes up sleeping herpes viruses – but how?

February 24, 2016
Hiding their DNA genome inside the nuclei of the infected cells, the herpes viruses establish a lifelong infection in humans. Poorly defined stress conditions are known to wake up these parasites from their latent phase and ...

Recommended for you

Human 'chimeric' cells restore crucial protein in Duchenne muscular dystrophy

March 16, 2018
Cells made by fusing a normal human muscle cell with a muscle cell from a person with Duchenne muscular dystrophy —a rare but fatal form of muscular dystrophy—were able to significantly improve muscle function when implanted ...

Team develops 3-D tissue model of a developing human heart

March 16, 2018
The heart is the first organ to develop in the womb and the first cause of concern for many parents.

Genetic variant discovery to help asthma sufferers

March 16, 2018
Research from the University of Liverpool, published today in Lancet Respiratory Medicine, identifies a genetic variant that could improve the safety and effectiveness of corticosteroids, drugs that are used to treat a range ...

Researchers say use of artificial intelligence in medicine raises ethical questions

March 15, 2018
In a perspective piece, Stanford researchers discuss the ethical implications of using machine-learning tools in making health care decisions for patients.

Study identifies potential drug for treatment of debilitating inherited neurological disease

March 15, 2018
St. Jude Children's Research Hospital scientists have demonstrated in mouse studies that the neurological disease spinal bulbar muscular atrophy (SBMA) can be successfully treated with drugs. The finding paves the way for ...

Clearing clumps of protein in aging neural stem cells boosts their activity

March 15, 2018
Young, resting neural stem cells in the brains of mice store large clumps of proteins in specialized cellular trash compartments known as lysosomes, researchers at the Stanford University School of Medicine have found.


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.