Finding the mutations that drive resistance

Factors that drive HCV resistance to DAAs

Direct-acting antiviral (DAA) agents specifically target viral proteins. Two DAAs have been already been approved for the treatment of HCV infection and many more are in development. DAA treatment of HCV infection, however, leads to the selection of viral variants (produced by the error-prone HCV polymerase) that are resistant to the DAA agent in use. The selection of DAA-resistant HCV variants...

Genetic Mutations that Cause Coronary Artery Disease

Human mutations that confer paclitaxel resistance.

The involvement of tubulin mutations as a cause of clinical drug resistance has been intensely debated in recent years. In the studies described here, we used transfection to test whether beta1-tubulin mutations and polymorphisms found in cancer patients are able to confer resistance to drugs that target microtubules. Three of four mutations (A185T, A248V, R306C, but not G437S) that we tested c...

Finding NEMO mutations

1620 JEM Vol. 203, No. 7, 2006 When confronted with potentially lethal bacterial sepsis, the brain tells the spleen to shut down the production of inflammatory cytokines, according to Huston and colleagues on page 1623. This may help explain why splenectomy renders people more prone to the immunological overreaction of septic shock when infected with certain types of bacteria. When the brain de...

Cytomegalovirus UL97 kinase mutations that confer maribavir resistance.

The cytomegalovirus (CMV) UL97 kinase inhibitor maribavir (MBV) is undergoing clinical antiviral trials. Two clinical CMV isolates serially passaged in cell culture under MBV showed >20-fold increases in MBV resistance after the development of the UL97 mutation V353A in one of the isolates and of T409M in the other. Marker transfer studies confirmed that the V353A and T409M mutations conferred ...