Evolution of male pregnancy and immune remodeling
Seahorses (Hippocampus abdominalis) swimming in an aquarium. Image credit: Sarah Kaehlert (GEOMAR Helmholtz Centre for Ocean Research Kiel, Kiel, Germany).
In vertebrates, a developing embryo must avoid being recognized as foreign tissue by an immune system attuned to attack foreign antigens. Olivia Roth et al. (pp. 9431–9439) performed genomic analysis of seahorses and pipefishes to uncover links between the evolution of pregnancy and modification of the adaptive immune system. The authors analyzed the genomes of 12 species of seahorses and pipefishes representing a gradient of male pregnancy types, from external egg carrying to full internal gestation with a placenta-like structure. The comparative analysis of genomes along this gradient revealed divergent genomic rearrangements in the major histocompatibility complex class II (MHC II) pathway of species that become fully pregnant; the MHC II pathway is an immune system component implicated in immunological tolerance. In seahorses, a portion of the MHC II molecule, CD74, was significantly different from mammals, likely affecting its binding ability. In pipefish, the authors found that the pathway was interrupted, likely preventing the molecules from presenting foreign antigens to immune cells. According to the authors, this natural inactivation of the MHC II pathway could provide a helpful model for studying immune deficiencies, given that pipefishes survive with a drastically altered adaptive immune system. — T.H.D.
Pilot study of convalescent plasma therapy for COVID-19
No specific antiviral treatments exist for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19), creating a need for alternative treatment strategies. Kai Duan, Bende Liu, Huanjun Zhang, Ting Yu, Jieming Qu, Min Zhou, Li Chen, et al. (pp. 9490–9496) explored the feasibility of convalescent plasma (CP) therapy for COVID-19 treatment in a pilot study of 10 severe COVID-19 patients, aged 34–78 years. The enrolled patients received transfusion of one dose of 200 ml CP derived from recently recovered donors, containing high levels of SARS-CoV-2–neutralizing antibody. Within 3 days of CP transfusion, clinical symptoms, such as fever, cough, shortness of breath, and chest pain, significantly improved, and patients exhibited increased lymphocyte counts, improved liver and lung function, and reduced inflammation. Neutralizing antibody levels increased or remained high after CP transfusion. Within 7 days of transfusion, varying degrees of reabsorption of lung lesions were observed on chest CT scans. In addition, no serious adverse reactions were observed after CP transfusion. The results, though preliminary, suggest that CP therapy might be a safe and promising treatment for severe COVID-19 patients and support further investigation in randomized controlled clinical trials, according to the authors. — B.D.
Australian bats as retrovirus reservoirs
Electron micrograph of HPG following release from a human cell.
Bats serve as reservoirs for diverse types of viruses, but little is known about retrovirus circulation in bat populations. Retroviruses can integrate into the genetic material of host cells, often leaving a footprint of exposure in host genomes. Joshua Hayward, Mary Tachedjian, et al. (pp. 9529–9536) report koala retrovirus-related (KoRV-related) viruses circulating in eastern Australian bats and identified a novel retrovirus, suggesting that bats are reservoirs of the mammalian retroviruses. From 2007 to 2014, the authors collected 479 samples of feces, oral swabs, blood, and/or urine from bats along the east coast of Australia. Metagenomic analysis revealed the presence of KoRV-related viruses in samples from several bat species. Phylogenetic analysis of the bat viruses suggested that they are an early ancestor of KoRV-related viruses. The authors also isolated a novel KoRV-related virus, the Hervey pteropid gammaretrovirus (HPG), from one feces sample. Subsequent testing showed that the virus is capable of reproducing in vitro. The authors note that the identification of HPG demonstrates that retroviruses can actively reproduce in bats. Together with the footprints of the other KoRV-related viruses in the samples, the results suggest that bats are reservoirs of KoRV-related viruses, according to the authors. — T.H.D.
Model of mouse striatum could illuminate motor behavior
The striatum is a brain structure that plays a critical role in decision-making. Simulations that integrate multiple levels of biological detail are important for understanding striatal function, but previously developed computational models have focused on limited aspects of striatal anatomy. J. Johannes Hjorth, Alexander Kozlov, et al. (pp. 9554–9565) reconstructed a nearly full-scale model of the mouse striatum. More than 98% of striatal neurons were represented in the simulations, which spanned from the molecular, subcellular, and cellular levels to the large-scale network level. The simulations were based on experimental results providing detailed information on the morphology, density, ion channels, electrophysiological properties, synaptic connectivity, and short-term dynamics of most types of striatal neurons. The model represented five major cellular subtypes, including direct striatal projection neurons, indirect striatal projection neurons, fast-spiking interneurons, cholinergic interneurons, and low-threshold spiking interneurons. The authors used this information to simulate a microcircuit of 10,000 striatal neurons in action, driven by input from other brain regions, including the dopamine system, the thalamus, and cortex. According to the authors, the model could be used to shed light on the role of the striatum in normal behavior as well as psychiatric and neurological disorders such as Parkinson’s disease. — J.W.
Assessing risk of viral zoonoses
The propensity of a virus to spread to humans is thought to vary across nonhuman animal groups that act as reservoir hosts. However, the notion that certain animal groups disproportionately maintain and transmit viruses to humans is debated. To test this idea, Nardus Mollentze and Daniel Streicker (pp. 9423–9430) conducted literature searches and constructed a large dataset of 415 species of RNA and DNA viruses from 30 viral families that have infected three avian and eight mammalian orders. The authors found that the proportion of viruses that are zoonotic does not vary substantially across taxonomic orders. Compared with orders that consist of fewer animal species, species-rich orders harbor more human-infecting viruses, but this number scales proportionately with the total number of viruses. Bats and rodents, which are widely considered to be special reservoirs, harbor close to the number of human-infecting viruses expected from their species richness. The findings suggest that certain features of virus biology, rather than physiological or ecological traits associated with reservoir hosts, are responsible for viral transmission to humans. The current practice of focusing virus discovery, research, and surveillance efforts on host reservoirs thought to pose a high risk should be broadened to be proportionate with local biodiversity, according to the authors. — J.W.