The extraordinary evolutionary history of the reticuloendotheliosis viruses

The reticuloendotheliosis viruses (REVs) comprise several closely related amphotropic retroviruses isolated from birds. These viruses exhibit several highly unusual characteristics that have not so far been adequately explained, including their extremely close relationship to mammalian retroviruses, and their presence as endogenous sequences within the genomes of certain large DNA viruses. We present evidence for an iatrogenic origin of REVs that accounts for these phenomena. Firstly, we identify endogenous retroviral fossils in mammalian genomes that share a unique recombinant structure with REVs—unequivocally demonstrating that REVs derive directly from mammalian retroviruses. Secondly, through sequencing of archived REV isolates, we confirm that contaminated Plasmodium lophurae stocks have been the source of multiple REV outbreaks in experimentally infected birds. Finally, we show that both phylogenetic and historical evidence support a scenario wherein REVs originated as mammalian retroviruses that were accidentally introduced into avian hosts in the late 1930s, during experimental studies of P. lophurae, and subsequently integrated into the fowlpox virus (FWPV) and gallid herpesvirus type 2 (GHV-2) genomes, generating recombinant DNA viruses that now circulate in wild birds and poultry. Our findings provide a novel perspective on the origin and evolution of REV, and indicate that horizontal gene transfer between virus families can expand the impact of iatrogenic transmission events

Structure of a highly conserved domain of rock1 required for shroom-mediated regulation of cell morphology

Rho-associated coiled coil containing protein kinase (Rho-kinase or Rock) is a well-defined determinant of actin organization and dynamics in most animal cells characterized to date. One of the primary effectors of Rock is non-muscle myosin II. Activation of Rock results in increased contractility of myosin II and subsequent changes in actin architecture and cell morphology. The regulation of Rock is thought to occur via autoinhibition of the kinase domain via intramolecular interactions between the N-terminus and the C-terminus of the kinase. This autoinhibited state can be relieved via proteolytic cleavage, binding of lipids to a Pleckstrin Homology domain near the C-terminus, or binding of GTP-bound RhoA to the central coiled-coil region of Rock. Recent work has identified the Shroom family of proteins as an additional regulator of Rock either at the level of cellular distribution or catalytic activity or both. The Shroom-Rock complex is conserved in most animals and is essential for the formation of the neural tube, eye, and gut in vertebrates. To address the mechanism by which Shroom and Rock interact, we have solved the structure of the coiled-coil region of Rock that binds to Shroom proteins. Consistent with other observations, the Shroom binding domain is a parallel coiled-coil dimer. Using biochemical approaches, we have identified a large patch of residues that contribute to Shrm binding. Their orientation suggests that there may be two independent Shrm binding sites on opposing faces of the coiled-coil region of Rock. Finally, we show that the binding surface is essential for Rock colocalization with Shroom and for Shroom-mediated changes in cell morphology. © 2013 Mohan et al

Buffered memory: a hypothesis for the maintenance of functional, virus-specific CD8(+) T cells during cytomegalovirus infection.

Chronic infections have been a major topic of investigation in recent years, but the mechanisms that dictate whether or not a pathogen is successfully controlled are incompletely understood. Cytomegalovirus (CMV) is a herpesvirus that establishes a persistent infection in the majority of people in the world. Like other herpesviruses, CMV is well controlled by an effective immune response and induces little, if any, pathology in healthy individuals. However, controlling CMV requires continuous immune surveillance, and thus, CMV is a significant cause of morbidity and death in immune-compromised individuals. T cells in particular play an important role in controlling CMV and both CD4(+) and CD8(+) CMV-specific T cells are essential. These virus-specific T cells persist in exceptionally large numbers during the infection, traffic into peripheral tissues and remain functional, making CMV an attractive vaccine vector for driving CMV-like T cell responses against recombinant antigens of choice. However, the mechanisms by which these T cells persist and differentiate while remaining functional are still poorly understood, and we have no means to promote their development in immune-compromised patients at risk for CMV disease. In this review, I will briefly summarize our current knowledge of CMV-specific CD8(+) T cells and propose a mechanism that may explain their maintenance and preservation of function during chronic infection

Alternative futures for global biological invasions

Scenario analysis has emerged as a key tool to analyze complex and uncertain future socio-ecological developments. However, currently existing global scenarios (narratives of how the world may develop) have neglected biological invasions, a major threat to biodiversity and the economy. Here, we use a novel participatory process to develop a diverse set of global biological invasion scenarios spanning a wide range of plausible global futures through to 2050. We adapted the widely used “two axes” scenario analysis approach to develop four families of four scenarios each, resulting in 16 scenarios that were later clustered into four contrasting sets of futures. Our analysis highlights that socioeconomic developments and technological innovation have the potential to shape biological invasions, in addition to well-known drivers, such as climate and human land use change and global trade. Our scenarios partially align with the shared socioeconomic pathways created by the climate change research community. Several factors that drive differences in biological invasions were underrepresented in the shared socioeconomic pathways; in particular, the implementation of biosecurity policies. We argue that including factors related to public environmental awareness and technological and trade development in global scenarios and models is essential to adequately consider biological invasions in global environmental assessments and thereby obtain a more integrative picture of future social–ecological developments

Biodiversity impacts of the 2019-2020 Australian megafires.

With large wildfires becoming more frequent1,2, we must rapidly learn how megafires impact biodiversity to prioritize mitigation and improve policy. A key challenge is to discover how interactions among fire-regime components, drought and land tenure shape wildfire impacts. The globally unprecedented3,4 2019-2020 Australian megafires burnt more than 10 million hectares5, prompting major investment in biodiversity monitoring. Collated data include responses of more than 2,000 taxa, providing an unparalleled opportunity to quantify how megafires affect biodiversity. We reveal that the largest effects on plants and animals were in areas with frequent or recent past fires and within extensively burnt areas. Areas burnt at high severity, outside protected areas or under extreme drought also had larger effects. The effects included declines and increases after fire, with the largest responses in rainforests and by mammals. Our results implicate species interactions, dispersal and extent of in situ survival as mechanisms underlying fire responses. Building wildfire resilience into these ecosystems depends on reducing fire recurrence, including with rapid wildfire suppression in areas frequently burnt. Defending wet ecosystems, expanding protected areas and considering localized drought could also contribute. While these countermeasures can help mitigate the impacts of more frequent megafires, reversing anthropogenic climate change remains the urgent broad-scale solution

Varicella zoster virus glycoprotein C increases chemokine-mediated leukocyte migration

Varicella zoster virus (VZV) is a highly prevalent human pathogen that establishes latency in neurons of the peripheral nervous system. Primary infection causes varicella whereas reactivation results in zoster, which is often followed by chronic pain in adults. Following infection of epithelial cells in the respiratory tract, VZV spreads within the host by hijacking leukocytes, including T cells, in the tonsils and other regional lymph nodes, and modifying their activity. In spite of its importance in pathogenesis, the mechanism of dissemination remains poorly understood. Here we addressed the influence of VZV on leukocyte migration and found that the purified recombinant soluble ectodomain of VZV glycoprotein C (rSgC) binds chemokines with high affinity. Functional experiments show that VZV rSgC potentiates chemokine activity, enhancing the migration of monocyte and T cell lines and, most importantly, human tonsillar leukocytes at low chemokine concentrations. Binding and potentiation of chemokine activity occurs through the C-terminal part of gC ectodomain, containing predicted immunoglobulin-like domains. The mechanism of action of VZV rSgC requires interaction with the chemokine and signalling through the chemokine receptor. Finally, we show that VZV viral particles enhance chemokine-dependent T cell migration and that gC is partially required for this activity. We propose that VZV gC activity facilitates the recruitment and subsequent infection of leukocytes and thereby enhances VZV systemic dissemination in humans

Chronic Viral Infection and Primary Central Nervous System Malignancy

Primary central nervous system (CNS) tumors cause significant morbidity and mortality in both adults and children. While some of the genetic and molecular mechanisms of neuro-oncogenesis are known, much less is known about possible epigenetic contributions to disease pathophysiology. Over the last several decades, chronic viral infections have been associated with a number of human malignancies. In primary CNS malignancies, two families of viruses, namely polyomavirus and herpesvirus, have been detected with varied frequencies in a number of pediatric and adult histological tumor subtypes. However, establishing a link between chronic viral infection and primary CNS malignancy has been an area of considerable controversy, due in part to variations in detection frequencies and methodologies used among researchers. Since a latent viral neurotropism can be seen with a variety of viruses and a widespread seropositivity exists among the population, it has been difficult to establish an association between viral infection and CNS malignancy based on epidemiology alone. While direct evidence of a role of viruses in neuro-oncogenesis in humans is lacking, a more plausible hypothesis of neuro-oncomodulation has been proposed. The overall goals of this review are to summarize the many human investigations that have studied viral infection in primary CNS tumors, discuss potential neuro-oncomodulatory mechanisms of viral-associated CNS disease and propose future research directions to establish a more firm association between chronic viral infections and primary CNS malignancies

Expanding the protected area network in Antarctica is urgent and readily achievable

The terrestrial protected areas of Antarctica are generally small, unrepresentative of the continent's biodiversity, and at risk from a range of pressures. While some consider the whole Antarctic region as a protected area, we demonstrate that the evidence does not support this view. The Protocol on Environmental Protection to the Antarctic Treaty recognizes that a systematic environmental-geographical framework provides a quantitative approach to inform expansion of the current Antarctic Specially Protected Area (ASPA) network. We review the progress thus far and challenges facing the establishment of protected areas in terrestrial Antarctica when adopting best practice approaches, an assessment that is lacking for the region to date. Encouragingly, because of the historical investment in Antarctic biodiversity science, and the existence and implementation of defined processes to identify and designate ASPAs, the opportunity exists to rapidly expand the current ASPA network. However, challenges remain. Foremost amongst these is the adoption of a comprehensive systematic conservation plan by stakeholders. We outline a strategy for the Antarctic Treaty Parties to provide the equitable, effective, transparent and scientifically founded expansion of protected areas that Antarctica urgently requires. We also highlight where opportunities for co-learning may lie in conservation planning and policy development in the Antarctic and other commons or commons-like areas

Surprising results on phylogenetic tree building methods based on molecular sequences

BACKGROUND: We analyze phylogenetic tree building methods from molecular sequences (PTMS). These are methods which base their construction solely on sequences, coding DNA or amino acids. RESULTS: Our first result is a statistically significant evaluation of 176 PTMSs done by comparing trees derived from 193138 orthologous groups of proteins using a new measure of quality between trees. This new measure, called the Intra measure, is very consistent between different groups of species and strong in the sense that it separates the methods with high confidence. The second result is the comparison of the trees against trees derived from accepted taxonomies, the Taxon measure. We consider the NCBI taxonomic classification and their derived topologies as the most accepted biological consensus on phylogenies, which are also available in electronic form. The correlation between the two measures is remarkably high, which supports both measures simultaneously. CONCLUSIONS: The big surprise of the evaluation is that the maximum likelihood methods do not score well, minimal evolution distance methods over MSA-induced alignments score consistently better. This comparison also allows us to rank different components of the tree building methods, like MSAs, substitution matrices, ML tree builders, distance methods, etc. It is also clear that there is a difference between Metazoa and the rest, which points out to evolution leaving different molecular traces. We also think that these measures of quality of trees will motivate the design of new PTMSs as it is now easier to evaluate them with certainty