A New Breast Cancer Model

PLoS Biology | http://biology.plosjournals.org Of the 300 or so viruses that cause disease in humans, HIV may have the greatest adaptive advantage. Like most persistent viruses—including the herpesviruses Epstein–Barr and cytomegalovirus (CMV)—HIV employs various strategies to counteract its host’s response to infection. But HIV possesses a unique ability to sustain a progressive attack on the immune system—infecting the very cells that coordinate the immune response—leaving the body susceptible even to normally harmless microorganisms. It is these so-called opportunistic infections, rather than the human immunodefi ciency virus itself, that makes HIV so deadly. The specifi c mechanisms that engineer this ongoing systemic attack have been the subject of intense research. HIV targets white blood cells with protein surface receptors called CD4. These CD4, or helper, T-cells normally orchestrate the body’s immune response by signaling killer T-cells (which are also called CD8 T-cells, after their CD8 surface receptors) and other immune cells to multiply and differentiate—that is, become specially equipped to recognize a particular pathogen, or antigen. At the onset of infection, the immune system appears to respond normally, with a strong attack led by HIV-specifi c CD8 T-cells that initially contain the virus. But as the infection progresses, CD4 counts drop and the body’s ability to renew T-cells decreases while its proportion of “antigen-experienced’’ CD8 T-cells increases. While the biological effect of this hyperactivity is unclear, it is apparent that patients with elevated immune activity face a poor prognosis. Investigating the interaction among immune activation, CD8 T-cell differentiation, and HIV prognosis, Victor Appay and colleagues report that a close connection between elevated immune activation and elevated levels of highly differentiated T-cells may bring further insights into how HIV exhausts the immune system. To examine the effect of elevated immune activation on T-cells, the researchers analyzed T-cells from a group of HIV-infected individuals collected at two distinct points in time: at the onset of acute infection—which is characterized