Research brief

Abstract

Results of a phase 1 study in 12 aviraemic HIV-positive patients receiving antiretroviral therapy (ART) suggest that it might be possible to use gene editing to induce genetic resistance to HIV infection. Researchers used a targeted zinc-finger nuclease to inactivate the chemokine (C-C motif) receptor 5 gene (CCR5), which encodes a coreceptor for HIV entry, in autologous CD4 T cells. The modified cells persisted well after adoptive transfer into the patients. In six patients in whom ART was interrupted, the decline of modified cells was less than that of unmodified cells during the resultant viraemia. Moreover, the viral load in four of these six patients subsequently decreased. Could permafrost thawing as a result of climate change threaten human health? Researchers have isolated a new giant DNA virus (pithovirus sibericum) from a sample of Siberian permafrost more than 30 000 years old. The virus, which is visible under a light microscope, was isolated using acanthamoeba as bait and is the third type of giant virus to be isolated. Its revival suggests that other ancient viruses, some of which could be pathogenic to people, might be revived as increasing global temperatures melt the permafrost. A temporal and geographical survey of camels in Saudi Arabia suggests that the Middle East respiratory syndrome (MERS) coronavirus, which first emerged in this region, is widespread in dromedary camels (but is absent in sheep and goats) and has been circulating in camels in this country since 1992. Investigators of a second study report that viruses very similar to those implicated in human outbreaks of MERS in the Arabian Peninsula are infecting dromedary camels in Egypt, a region where no MERS cases have been reported yet. Antibiotic molecules bind to bacterial cell walls and induce stress, which contributes to cell wall breakdown. Competing molecules such as serum proteins affect the binding of antibiotics to bacteria, thereby reducing antibiotic efficacy in vivo. Now, researchers report that nanomechanical cantilevers can be used as surface-stress tensors to measure the concentration of free active vancomycin and oritavancin (which is in clinical development for the treatment of vancomycin-resistant infections) in human serum. This approach could be used diagnostically to determine how much and which antibiotic to give to individual patients. Because both the malaria parasite and its insect vectors are sensitive to temperature, cold temperatures slow down the transmission rate of malaria. Experts predict, therefore, that the altitudinal range of malaria should increase in response to global warming. An examination of the association between the spatial distribution of malaria and the interannual variability of temperature in the heavily populated highlands of Ethiopia and Columbia reveals that, as predicted, more cases of malaria occurred at higher altitudes in warmer years. Thus, climate change is likely to increase the malaria burden substantially in these regions. The emergence of metabolic resistance to insecticides in malaria vectors poses a large threat to global malaria control efforts, but its molecular basis is poorly characterised. Researchers now report that a single mutation in the gene encoding an upregulated glutathione S-transferase gene (GSTe2) confers a high level of resistance to both dichlorodiphenyltrichoroethane (DDT) and pyrethroids in the malaria vector Anopheles funestus. The identification of the mutation, which causes an aminoacid change that enlarges the binding site for DDT in GSTe2, provides a method by which vector control programmes could track the emergence of metabolically based insecticide resistance. During malaria transmission, plasmodium parasites switch from an asexual form that replicates in mammalian erythrocytes into non-dividing gametocytes that are transmitted through mosquitoes. New research describes a transcriptional switch that underlies this process. One study identifies PfAP2-G, a conserved member of the apicomplexan AP2 (ApiAP2) family of DNA-binding proteins, as a master regulator of sexual development in Plasmodium falciparum. A second study reports that a cascade of ApiAP2 proteins that includes PbAP2-G is required for sexual development in P berghei. Interference with this conserved transcriptional switch could provide new ways to break the malaria transmission cycle.