Children’s National identifies trigger for alternate reproduction of HIV-related cancer virus

[ Back to EurekAlert! ] Public release date: 17-Apr-2012
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Contact: Emily Hartman
ehartman@childrensnational.org
202-476-4500
Children’s National Medical Center

Findings show that Kaposi’s sarcoma-associated herpesvirus senses and reacts to a host cell’s impending death

WASHINGTON, DC A research team led by Children’s National Medical Center has identified a trigger that causes latent Kaposi’s sarcoma-associated herpesvirus (KSHV) to rapidly replicate itself. KSHV causes Kaposi’s sarcoma, primary effusion lymphoma, and other cancers that commonly affect immunocompromised patients, including those with AIDS. Appearing in the online edition of the Journal of Virology, the study identifies apoptosis, or the programmed death of a virus’ host cell, as the trigger for high-level viral replication.

“Finding that the programmed death of a host cell triggered rapid production of Kaposi’s sarcoma-associated herpesvirus, means that KSHV has the ability to sense and respond to critical changes in the cells that it grows in, something we didn’t know before,” stated lead author Alka Prasad, PhD, who is a member of the Center for Cancer and Immunology Research at Children’s National Medical Center. “We previously thought that the virus was more of an inanimate entity. This newly discovered pathway is clearly helpful to the virus and clues researchers in on how we might target treatments. If the host cell died quickly, before the virus could reproduce, then the virus could not infect any new cells. Having the ability to sense when the host cell is about to die and reproduce quickly in response gives the virus an evolutionary advantage. In addition, cancers caused by KSHV and other herpesviruses are commonly treated with drugs that kill cells, so the results could have a significant effect on the treatment of KSHV-related cancers, which we will need to explore.”

KSHV and the cancers it causes most commonly afflict patients with AIDS and other disorders that impact the immune system. KSHV attaches to white blood cells and either actively replicates through a controlled gene expression program or remains latent. A specific genetic protein in the virus, called an ORF50 gene product, is thought to control the transition from latency to replication. Using a derivative of this specific protein that blocks gene expression and replication, the scientists found that when apoptosis was induced, KSHV replicated itself. They also discovered that whether this derivative was present or not, apoptopsis induced the virus’ replication.

“In addition to looking at the clinical implications of these research findings, we now need to focus in on the pathway that links apoptosis to this particular replication pathway and perhaps expand our research from KSHV to include another example of herpesvirus,” commented Steven Zeichner, MD, PhD, the senior author on the paper, who is a principal investigator for the Center for Cancer and Immunology Research at Children’s National and a professor at the George Washington University School of Medicine. The study was supported in part by the new NIH-funded District of Columbia Center for AIDS Research, of which Children’s National is a key member.

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[ Back to EurekAlert! ] Public release date: 17-Apr-2012
[ | E-mail | Share Share ]

Contact: Emily Hartman
ehartman@childrensnational.org
202-476-4500
Children’s National Medical Center

Findings show that Kaposi’s sarcoma-associated herpesvirus senses and reacts to a host cell’s impending death

WASHINGTON, DC A research team led by Children’s National Medical Center has identified a trigger that causes latent Kaposi’s sarcoma-associated herpesvirus (KSHV) to rapidly replicate itself. KSHV causes Kaposi’s sarcoma, primary effusion lymphoma, and other cancers that commonly affect immunocompromised patients, including those with AIDS. Appearing in the online edition of the Journal of Virology, the study identifies apoptosis, or the programmed death of a virus’ host cell, as the trigger for high-level viral replication.

“Finding that the programmed death of a host cell triggered rapid production of Kaposi’s sarcoma-associated herpesvirus, means that KSHV has the ability to sense and respond to critical changes in the cells that it grows in, something we didn’t know before,” stated lead author Alka Prasad, PhD, who is a member of the Center for Cancer and Immunology Research at Children’s National Medical Center. “We previously thought that the virus was more of an inanimate entity. This newly discovered pathway is clearly helpful to the virus and clues researchers in on how we might target treatments. If the host cell died quickly, before the virus could reproduce, then the virus could not infect any new cells. Having the ability to sense when the host cell is about to die and reproduce quickly in response gives the virus an evolutionary advantage. In addition, cancers caused by KSHV and other herpesviruses are commonly treated with drugs that kill cells, so the results could have a significant effect on the treatment of KSHV-related cancers, which we will need to explore.”

KSHV and the cancers it causes most commonly afflict patients with AIDS and other disorders that impact the immune system. KSHV attaches to white blood cells and either actively replicates through a controlled gene expression program or remains latent. A specific genetic protein in the virus, called an ORF50 gene product, is thought to control the transition from latency to replication. Using a derivative of this specific protein that blocks gene expression and replication, the scientists found that when apoptosis was induced, KSHV replicated itself. They also discovered that whether this derivative was present or not, apoptopsis induced the virus’ replication.

“In addition to looking at the clinical implications of these research findings, we now need to focus in on the pathway that links apoptosis to this particular replication pathway and perhaps expand our research from KSHV to include another example of herpesvirus,” commented Steven Zeichner, MD, PhD, the senior author on the paper, who is a principal investigator for the Center for Cancer and Immunology Research at Children’s National and a professor at the George Washington University School of Medicine. The study was supported in part by the new NIH-funded District of Columbia Center for AIDS Research, of which Children’s National is a key member.

###


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?

AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.

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PFT: Griffin has ‘superior arm talent’ to Luck

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The NFL?s owners will begin to convene in Palm Beach on Sunday for the league?s annual meetings.

Hovering over the proceedings will be the decision to remove $46 million in total cap space from the Cowboys ($10 million) and Redskins ($36 million) over the next two seasons for their accounting practices during the uncapped year of 2010.

The league has admitted to the Redskins that the teams did nothing wrong and violated no rules.? Still, the NFL contends that treating the term ?uncapped year? too literally disrupted competitive balance ? even though the decision of multiple teams to grossly underspend in 2010 apparently gave rise to no such concerns.

The Redskins have been working to rectify the situation, privately communicating with the league and separately making plans for potential litigation.? But while no Redskins official has said anything publicly about the situation, Cowboys owner Jerry Jones opted on Friday to put the rest of the league on notice that he won?t take this one lying down.

And he shouldn?t.

As we understand it, the teams will try at the league meetings to lobby other owners, making the case for some adjustment to the punishment sans crime.? If, in the end, the Redskins and Cowboys get nowhere, litigation could occur.

?[T]here is no joy in Mudville, having to team up with the Redskins on a point with the league,? Jones told the Dallas Morning News. ?They?re competitors, not cohorts.? It just shows you, independent of that, some of the issues we have with this cap-space issue.? Sometimes you can have strange bedfellows and this is one of them.?

The situation has several curiosities, which include a decision by the league to offer to the NFLPA the Redskins/Cowboys cap penalties in exchange for an increase in total cap space for 2012, and the absence of an ownership vote on the measure.? As one league source previously explained it to PFT, the mere act of conducting a vote would have given Jones and Redskins owner Dan Snyder an opportunity to attempt to secure the support of seven other teams, which then would have prevented the NFL from securing the necessary 24 votes to push the measure through.? (It also would have forced those teams that wanted to take cap space from the Cowboys and Redskins to go on record with a vote in favor of the move.)

In our view, the league needs to fix this before it spirals out of control.? It?s now obvious that the NFL was engaged in collusion in the uncapped year, trying to keep more money in the owners? pocket and less in the players? as a possible year without football loomed.? Still, forcing the Redskins and Cowboys to reduce to writing an allegation that the NFL and its teams tried to rein in spending and is now punishing the two that refused to go along with the illegal plan won?t be good for business.

Indeed, it won?t be good for anybody.

Source: http://profootballtalk.nbcsports.com/2012/03/24/cosell-deems-rg3-a-superior-arm-talent-and-natural-passer-to-luck/related/

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