Amsterdam, June 6th 2013
Also this week MedZine brings you the latest medical news on various medical specialisms. In this editorial some striking studies are highlighted, which are published in Cell. Two studies describe how bird flu viruses adapt to humans and how this offers strategies for surveillance and vaccines. The last study reports on the importance of CDK8 for the survival of tumor cells in an environment with low-oxygen.
A broad-spectrum vaccine against a sugar polymer
Currently, bird flu viruses form a global threat. The avian influenza viruses do not normally infect humans, but over time they can adapt to humans and gain the ability to spread more easily from person to person. In two publications in Cell, Tharakaraman and colleagues identify mutations that increase the infectivity of H5N1 and H7N9 viruses through improved binding to receptors in the human respiratory tract. There have been several outbreaks of the H5N1 virus in the last years. Almost 600 people were infected and 60% of them died. Lately, the H7N9 virus has infected at least 131 people. The researchers analyzed the structure of the H5N1 and H7N9 viruses, focusing on hemagglutinin (HA), which binds to receptors on cells in the respiratory tract of hosts. A set of HA mutations required to increase the preference of the viruses for human receptors were characterized. This requires only a single amino acid change in the HA sequence. Moreover, they found that distinct HA mutations are evolving in the H7N9 virus, making current vaccines not effective against this new virus. These findings can be used to monitor the evolution of H5N1 and H7N9 viruses and for developing more effective vaccines.
CDK8 controls gene expression needed to survive low-oxygen conditions
In the middle parts of tumors there is often a shortage of oxygen. Tumor cells activate a gene expression program that helps them survive hypoxic conditions. HIF1A is a master regulator of a cell's response to hypoxia and play an important role in tumor development, but it is hard to drug. Espinosa and this team were investigating the basic biology of a protein complex called Mediator and specifically the CDK8 component of this complex. The researcher found that cells fail to activate the genes needed for survival under low-oxygen when these lack CDK8. Moreover, the found that HIF1A works through CDK8. CDK8 is a kinase and there are kinase inhibitors known that inhibit enzymes similar to CDK8, making CDK8 a candidate drug target for cancer therapy.
Sources: Eurekalert and Cell