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Epstein-Barr virus betrays its secrets
Newsdesk Epstein-Barr virus betrays its secrets
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Courtesy of Paul Lieberman
Active replicon Scientists have uncovered how affecting the normal functions of Epstein-Barr virus (EBV) manthese proteins could be found, TRF2 TRF2 TRF2 EBNA1 EBNA1 EBNA1 EBNA1 ages to survive in host cells for then that might affect tumour hRap1 Tankyrase Tankyrase hRap1 Tankyrase hRap1 years without losing its genomic growth.” stability. The virus uses a subset Lieberman says this is exactly Genotoxic of the same proteins involved in what they are working on. “We stress human telomere function and were able to destabilise the viral Inactive replicon stability of the human genome. genome a little bit using certain TRF2 TRF2 EBNA1 EBNA1 EBNA1 EBNA1 TRF2 EBV can be maintained in chemicals that induce PARP, like hRap1 Tankyrase Tankyrase hRap1 Tankyrase hRap1 proliferating cells for many hydroxyurea or hydrogen pergenerations by existing as a nonoxide. We are trying to find integrated plasmid in the whether or not these compounds Poly-ADP-Ribose nucleus. This is surprising and other pharmacological because mammalian cells usually EBV replication: a target for modifing tumour growth? agents that inhibit PARP can destroy non-integrated DNA really be useful in manipulating understood, and if something that viral genome stability.” very rapidly. Paul Lieberman and coprevented that interaction without Martina Habeck workers (Wistar Institute, PA, USA) were intrigued to find out how EBV protects itself against this destruction. It was already known that the EBVQuestion marks over NSAID efficacy encoded replication protein 1 (EBNA1) The nonsteroidal anti-inflammatory the treatment of choice. is important in this process. When the drug (NSAID) sulindac may not have host cell is about to divide, EBNA1 Marcia Cruz-Correa, from the the preventive properties for colon Division of Gastroenterology at Johns binds to the viral DNA site where cancer that were previously hoped for, Hopkins University (MD, USA), replication begins and ensures that the according to new findings investigating recently published findings showing viral genome is replicated at the same adenomas in people with familial that long-term use of sulindac was time as the host cell genome. adenomatous polyposis (FAP). Lieberman decided to look for effective in reducing polyp number and There is strong evidence that long- preventing recurrence of higher-grade cellular components that might help term use of NSAIDs is associated with a adenomas in a study of 12 adults EBNA1. He found some proteins that substantial reduction in the risk of phenotypically affected with FAP are typically associated with human colorectal cancer, with 30 of 32 (Gastroenterology 2002; 122: 641–45). telomeres: telomeric repeat binding facepidemiological studies showing a tor 2 (TRF2), tankyrase (a telomereShe maintains her belief that there protective effect against adenomatous is a role for long-term use of sulindac in associated poly(ADP-ribose) polypolyps, invasive cancer, or both. A new regression and prevention of colorectal merase [PARP]), and human Rap1 study by US researchers however, has cancer in individuals with FAP, (hRap1) (Molecular Cell 2002; 9: looked at whether NSAIDs could suggesting that the dose of sulindac 493–503). He also found that the viral prevent adenomas in patients with the used in the latest study may have been genome could be destroyed if TRF2 did FAP genotype but not the FAP too low to attain a sufficient reduction not bind to the viral DNA, and that phenotype. PARP modified EBNA1 in some way, in the prostaglandin level and to 41 participants received either 75 or prevent adenomas. which affected plasmid maintenance. 150 mg of sulindac twice a day, or a “I think these findings are Graeme Young (Flinders placebo, for 48 months. After four University, Adelaide, Australia), who is important for understanding EBV years of treatment, the mucosal currently recruiting for an international survival strategies,” says Lieberman. prostaglandin levels were lower in the trial of celecoxib to prevent sporadic “But they also suggest that EBV may be treatment group compared with the colonic polyps, agrees that the new a good model for studying how placebo group (NEJM 2002; 346: findings do not “put a cap on” research telomeres work and how they protect 1054–59) but there was no significant into the use of NSAIDS to prevent the genome.” difference between the mean number colon cancer. Paul Farrell, (Imperial College of or size of polyps in the two groups. Medicine, London, UK), agrees that “Simply because it doesn’t Adenomas developed in 43% of people convincingly work [in the current this work may help in this way. The treated with sulindac compared with study] doesn’t mean it doesn’t work in implications for the treatment of EBV55% receiving placebo. associated cancers, such as Burkitt’s sporadic adenoma,” he says. “We really The researchers suggested that need to wait to see other studies lymphoma or Hodgkin’s lymphoma, resistance may have developed against because it is a slightly different are less clear: “If the detailed sulindac, but conclude that molecular pathway.” biochemistry of how the telomeric prophylactic colectomy still remains Megan Howe proteins interact with EBNA1 were
THE LANCET Oncology Vol 3 May 2002
http://oncology.thelancet.com
For personal use. Only reproduce with permission from The Lancet Publishing Group.
260
a
4
3
b
2
1
b
a
4
3
b
2
1
b
Courtesy of Paul Lieberman
Active replicon Scientists have uncovered how affecting the normal functions of Epstein-Barr virus (EBV) manthese proteins could be found, TRF2 TRF2 TRF2 EBNA1 EBNA1 EBNA1 EBNA1 ages to survive in host cells for then that might affect tumour hRap1 Tankyrase Tankyrase hRap1 Tankyrase hRap1 years without losing its genomic growth.” stability. The virus uses a subset Lieberman says this is exactly Genotoxic of the same proteins involved in what they are working on. “We stress human telomere function and were able to destabilise the viral Inactive replicon stability of the human genome. genome a little bit using certain TRF2 TRF2 EBNA1 EBNA1 EBNA1 EBNA1 TRF2 EBV can be maintained in chemicals that induce PARP, like hRap1 Tankyrase Tankyrase hRap1 Tankyrase hRap1 proliferating cells for many hydroxyurea or hydrogen pergenerations by existing as a nonoxide. We are trying to find integrated plasmid in the whether or not these compounds Poly-ADP-Ribose nucleus. This is surprising and other pharmacological because mammalian cells usually EBV replication: a target for modifing tumour growth? agents that inhibit PARP can destroy non-integrated DNA really be useful in manipulating understood, and if something that viral genome stability.” very rapidly. Paul Lieberman and coprevented that interaction without Martina Habeck workers (Wistar Institute, PA, USA) were intrigued to find out how EBV protects itself against this destruction. It was already known that the EBVQuestion marks over NSAID efficacy encoded replication protein 1 (EBNA1) The nonsteroidal anti-inflammatory the treatment of choice. is important in this process. When the drug (NSAID) sulindac may not have host cell is about to divide, EBNA1 Marcia Cruz-Correa, from the the preventive properties for colon Division of Gastroenterology at Johns binds to the viral DNA site where cancer that were previously hoped for, Hopkins University (MD, USA), replication begins and ensures that the according to new findings investigating recently published findings showing viral genome is replicated at the same adenomas in people with familial that long-term use of sulindac was time as the host cell genome. adenomatous polyposis (FAP). Lieberman decided to look for effective in reducing polyp number and There is strong evidence that long- preventing recurrence of higher-grade cellular components that might help term use of NSAIDs is associated with a adenomas in a study of 12 adults EBNA1. He found some proteins that substantial reduction in the risk of phenotypically affected with FAP are typically associated with human colorectal cancer, with 30 of 32 (Gastroenterology 2002; 122: 641–45). telomeres: telomeric repeat binding facepidemiological studies showing a tor 2 (TRF2), tankyrase (a telomereShe maintains her belief that there protective effect against adenomatous is a role for long-term use of sulindac in associated poly(ADP-ribose) polypolyps, invasive cancer, or both. A new regression and prevention of colorectal merase [PARP]), and human Rap1 study by US researchers however, has cancer in individuals with FAP, (hRap1) (Molecular Cell 2002; 9: looked at whether NSAIDs could suggesting that the dose of sulindac 493–503). He also found that the viral prevent adenomas in patients with the used in the latest study may have been genome could be destroyed if TRF2 did FAP genotype but not the FAP too low to attain a sufficient reduction not bind to the viral DNA, and that phenotype. PARP modified EBNA1 in some way, in the prostaglandin level and to 41 participants received either 75 or prevent adenomas. which affected plasmid maintenance. 150 mg of sulindac twice a day, or a “I think these findings are Graeme Young (Flinders placebo, for 48 months. After four University, Adelaide, Australia), who is important for understanding EBV years of treatment, the mucosal currently recruiting for an international survival strategies,” says Lieberman. prostaglandin levels were lower in the trial of celecoxib to prevent sporadic “But they also suggest that EBV may be treatment group compared with the colonic polyps, agrees that the new a good model for studying how placebo group (NEJM 2002; 346: findings do not “put a cap on” research telomeres work and how they protect 1054–59) but there was no significant into the use of NSAIDS to prevent the genome.” difference between the mean number colon cancer. Paul Farrell, (Imperial College of or size of polyps in the two groups. Medicine, London, UK), agrees that “Simply because it doesn’t Adenomas developed in 43% of people convincingly work [in the current this work may help in this way. The treated with sulindac compared with study] doesn’t mean it doesn’t work in implications for the treatment of EBV55% receiving placebo. associated cancers, such as Burkitt’s sporadic adenoma,” he says. “We really The researchers suggested that need to wait to see other studies lymphoma or Hodgkin’s lymphoma, resistance may have developed against because it is a slightly different are less clear: “If the detailed sulindac, but conclude that molecular pathway.” biochemistry of how the telomeric prophylactic colectomy still remains Megan Howe proteins interact with EBNA1 were
THE LANCET Oncology Vol 3 May 2002
http://oncology.thelancet.com
For personal use. Only reproduce with permission from The Lancet Publishing Group.