Transforming with telomerase
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《实验药学杂志》
The telomerase RNA encoded by Marek's disease virus promotes tumor formation in chickens.
Viruses often transform their host cell so they can have a long-lasting and often mobile home. Now, Trapp et al. (page 1307) find that one chicken virus uses a hijacked telomerase RNA (TR) to trigger tumor formation.
Marek's disease virus (MDV)–a tumor-causing herpesvirus of chickens–costs the poultry industry an estimated $1 billion annually. Although vaccines against MDV exist, the crowded living conditions of commercially raised chickens have fostered the evolution of nastier, vaccine-resistant virus strains.
The design of better vaccines, however, requires a better understanding of how the virus triggers tumors. Transformation is driven in part by the viral protein Meq, a Jun/Fos-like oncoprotein. The virus also encodes its own TR (vTR)–most likely pirated from the chicken genome.
TR is part of the telomerase enzyme that adds protective ends–telomeres–onto chromosomes. Telomerase activity is increased in many human tumors, but whether this is a cause or an effect of transformation has never been firmly established.
Trapp and colleagues now provide the first evidence that a vTR can contribute directly to tumor formation in a natural animal model. Wild-type chickens infected with MDV strains lacking both copies of the TR gene, they show, were less likely to develop cancer despite normal virus replication. The tumors that did develop were less widely disseminated.
The vTR does not appear to promote tumor formation by adding extra length to chromosome ends, as cells expressing vTR had normal-length telomeres. One clue might be the increased expression of v integrins on vTR-expressing cells, as v integrins have been implicated in promoting metastasis.
Viruses often transform their host cell so they can have a long-lasting and often mobile home. Now, Trapp et al. (page 1307) find that one chicken virus uses a hijacked telomerase RNA (TR) to trigger tumor formation.
Marek's disease virus (MDV)–a tumor-causing herpesvirus of chickens–costs the poultry industry an estimated $1 billion annually. Although vaccines against MDV exist, the crowded living conditions of commercially raised chickens have fostered the evolution of nastier, vaccine-resistant virus strains.
The design of better vaccines, however, requires a better understanding of how the virus triggers tumors. Transformation is driven in part by the viral protein Meq, a Jun/Fos-like oncoprotein. The virus also encodes its own TR (vTR)–most likely pirated from the chicken genome.
TR is part of the telomerase enzyme that adds protective ends–telomeres–onto chromosomes. Telomerase activity is increased in many human tumors, but whether this is a cause or an effect of transformation has never been firmly established.
Trapp and colleagues now provide the first evidence that a vTR can contribute directly to tumor formation in a natural animal model. Wild-type chickens infected with MDV strains lacking both copies of the TR gene, they show, were less likely to develop cancer despite normal virus replication. The tumors that did develop were less widely disseminated.
The vTR does not appear to promote tumor formation by adding extra length to chromosome ends, as cells expressing vTR had normal-length telomeres. One clue might be the increased expression of v integrins on vTR-expressing cells, as v integrins have been implicated in promoting metastasis.