Identifying broadly neutralizing antibodies against infectious agents such as influenza A viruses, HIV, and Plasmodium falciparum that display impressive degrees of antigenic variation is a major focus of investigators developing therapeutics and vaccines for pathogens of importance in public health (Corti and Lanzavecchia, 2013). In a previous post, I discussed one study (Klein et al., 2013) illustrating the sorts of unanticipated types of mutations found for broadly neutralizing antibodies against HIV. Lanzavecchia and colleagues have now identified antibodies reactive with antigens encoded by different isolates of Plasmodium falciparum and expressed on infected erythrocytes (Nature, 2015). They find an unexpected source for the heavy chain variable domain amino acid sequences that confer the broad anti-malarial reactivity against proteins in the RIFIN family.
Category: Infection (Page 1 of 5)
Clinical organ transplantation is now a large medical enterprise, with more than 29,000 organ transplants performed in 2014 in the United States alone (https://www.unos.org/data/transplant-trends/#transplants_by_organ_type+year+2014). Nevertheless, the number of organ donors is insufficient to meet the demand for new organs. For example, in the U.S. during 2014, there were 17,104 kidney transplants but 101,035 individuals on the waiting list for such transplants. Therefore, a recent study in Science (Yang et al., 2015) offers an important proof of principle for a necessary but not necessarily sufficient step on the path to safely using pig organs to substitute for failing human organs.
Last month, Murphy and colleagues (Cell, 2015) published a fascinating report about a patient with an immunodeficiency syndrome that underwent spontaneous resolution. The mechanism for this remarkable outcome points to the importance of somatic cell selection and evolution in the origins, pathogenesis, and most dramatically in this case, elimination of disease.
Iron is a critical metal for essential cellular processes, such as respiration, in both human and microbial cells. Thus, in the context of infection, iron is a high-value cellular commodity and an evolutionist might reasonably expect a metallic tug-of-war between host and pathogen iron-binding proteins or other iron-binding molecules (siderophores). This speculation is impressively supported in a paper published this month (Barber and Elde, 2014). These authors provide strong evidence for positive selection affecting several sites in host (transferrin, Tf) and pathogen (transferrin binding protein A) iron-binding proteins based on a combination of genetic, structural, and functional experimental methods.
An article published online at the Nature web site on November 24 (Chou et al., 2014) presents a fascinating study of examples in which bacterial genes have found their way to a number of distinct eukaryotic lineages including ticks and mites, gastropod (e.g., snails and slugs) and bivalve mollusks (e.g. clams and oysters), and choanoflagellates (a subset of ptotozoans). Type VI secretion amidase effector (Tae) molecules (encoded by tae genes) can kill rival bacteria by degrading their cells walls when delivered into those competing cells. The eukaryotes cited above all have “domesticated amidase effectors” (dae) genes, all of which are extremely similar to one of the four extant bacterial tae genes. Of the four tae genes found in bacterial species, three have been transferred to one or another eukaryotic genome.
After posting my last commentary on the ongoing Ebola outbreak in West Africa, I listened to the netcast, This Week in Virology (www.twiv.tv), for September 14, 2014. TWiV sessions, hosted by Vincent Racaniello, a well-known virologist at Columbia University, are generally highly informative, typically offering thoughtful discussions about recently published studies pertaining to viruses or addressing broad areas of virus-related research.