In Science this week, a team of academic and industry researchers report on the use of new imaging technique to understand how a key HIV protein can change its shape to facilitate infection. Using single-molecule FRET, the investigators were able to visualize the dynamic changes in the HIV-1 envelope protein Env and found that before the virus enters a host cell, the protein shifts between three different shapes. By focusing on two HIV-1 isolates — one sensitive to therapeutic antibodies and one resistant to them — and discovered that in the presence of an antibody, the drug-sensitive isolate transitioned from a ground-state configuration to an open one that permitted fusion with and infection of cells. This vulnerable open state, however, was masked in the antibody-resistant isolate.
Also in Science, two research groups publish studies that may help explain why non-small cell lung cancer (NSCLC) is so difficult to treat. In one report, scientists analyzed the genome of 25 distinct regions of seven different NSCLCs and found that the regions often displayed distinct copy number alterations, translocations, and mutations. Tumors from chronic smokers indicated that smoking-related mutations became less prevalent as the disease progressed, while tumors from individuals who had smoked for a little while then quit indicated that the lung damage occurred long ago and that a period of tumor latency preceded their diagnosis. In the other study, the investigators used whole-exome sequencing to study 11 lung cancers, discovering about 76 percent of all mutations were present in the tumors. Among three patients who relapsed after surgery, all had significantly larger fractions of sub-clonal mutations in their tumors compared to patients who had not relapsed. GenomeWeb Daily News has more on these studies here.