Thomas Siegmund Postler

In April 2024, following the annual International Committee on Taxonomy of Viruses (ICTV) ratification vote on newly proposed taxa, the phylum Negarnaviricota was expanded by 1 new order, 1 new family, 6 new subfamilies, 34 new genera and 270 new species. One class, two orders and six species were renamed. Seven families and 12 genera were moved; ten species were renamed and moved; and nine species were abolished. This article presents the updated taxonomy of Negarnaviricota as currently accepted by the ICTV, providing an essential annual update on the classification of members of this phylum that deepen understandings of their evolution, and supports critical public health measures for virus identification and tracking.

Background/Objectives: Orthoebolaviruses and orthomarburgviruses are filoviruses that can cause viral hemorrhagic fever and significant morbidity and mortality in humans. The evaluation and deployment of vaccines to prevent and control Ebola and Marburg outbreaks must be informed by an understanding of the transmission and natural history of the causative infections, but little is known about the burden of asymptomatic infection or undiagnosed disease. This systematic review of the published literature examined the seroprevalence of antibodies to orthoebolaviruses and orthomarburgviruses in sub-Saharan Africa. Methods: The review protocol was registered on PROSPERO (ID: CRD42023415358) and previously published. Eighty-seven articles describing 85 studies were included, of which seventy-six measured antibodies to orthoebolaviruses and forty-one measured antibodies to orthomarburgviruses. Results: The results highlight three central findings that may have implications for vaccine development and deployment. First, substantial antibody seropositivity to Ebola virus (EBOV) and Sudan virus (SUDV) was observed in populations from outbreak-affected areas (≤33% seroprevalence among general populations; ≤41% seroprevalence among healthcare workers and close contacts of disease cases). Second, antibody seropositivity to EBOV, SUDV, and Marburg virus (MARV) was observed among populations from areas without reported outbreaks, with seroprevalence ranging from <1 to 21%. Third, in Central and East Africa, MARV antibody seroprevalence was substantially lower than EBOV or SUDV antibody seroprevalence, even in outbreak-affected areas and in populations at a moderate or high risk of infection (with MARV seroprevalence mostly ranging from 0 to 3%). Conclusions: Whilst gaps remain in our understanding of the significance of antibody seropositivity in some settings and contexts, these findings may be important in considering target indications for novel filovirus vaccines, in defining study designs and strategies for demonstrating vaccine efficacy or effectiveness, and in planning and evaluating vaccine deployment strategies to prevent and control outbreaks.

The outcome of cancer and autoimmunity is often dictated by the effector functions of CD4+ conventional T cells (Tconv). Although activation of the NF-κB signaling pathway has long been implicated in Tconv biology, the cell-autonomous roles of the separate NF-κB transcription-factor subunits are unknown. Here, we dissected the contributions of the canonical NF-κB subunits RelA and c-Rel to Tconv function. RelA, rather than c-Rel, regulated Tconv activation and cytokine production at steady-state and was required for polarization toward the TH17 lineage in vitro. Accordingly, RelA-deficient mice were fully protected against neuroinflammation in a model of multiple sclerosis due to defective transition to a pathogenic TH17 gene-expression program. Conversely, Tconv-restricted ablation of c-Rel impaired their function in the microenvironment of transplanted tumors, resulting in enhanced cancer burden. Moreover, Tconv required c-Rel for the response to PD-1-blockade therapy. Our data reveal distinct roles for canonical NF-κB subunits in different disease contexts, paving the way for subunit-targeted immunotherapies.

Little is known about the pathobiology of SARS-CoV-2 infection in sub-Saharan Africa, where severe COVID-19 fatality rates are among the highest in the world and the immunological landscape is unique. In a prospective cohort study of 306 adults encompassing the entire clinical spectrum of SARS-CoV-2 infection in Uganda, we profile the peripheral blood proteome and transcriptome to characterize the immunopathology of COVID-19 across multiple phases of the pandemic. Beyond the prognostic importance of myeloid cell-driven immune activation and lymphopenia, we show that multifaceted impairment of host protein synthesis and redox imbalance define core biological signatures of severe COVID-19, with central roles for IL-7, IL-15, and lymphotoxin-α in COVID-19 respiratory failure. While prognostic signatures are generally consistent in SARS-CoV-2/HIV-coinfection, type I interferon responses uniquely scale with COVID-19 severity in persons living with HIV. Throughout the pandemic, COVID-19 severity peaked during phases dominated by A.23/A.23.1 and Delta B.1.617.2/AY variants. Independent of clinical severity, Delta phase COVID-19 is distinguished by exaggerated pro-inflammatory myeloid cell and inflammasome activation, NK and CD8⁺ T cell depletion, and impaired host protein synthesis. Combining these analyses with a contemporary Ugandan cohort of adults hospitalized with influenza and other severe acute respiratory infections, we show that activation of epidermal and platelet-derived growth factor pathways are distinct features of COVID-19, deepening translational understanding of mechanisms potentially underlying SARS-CoV-2-associated pulmonary fibrosis. Collectively, our findings provide biological rationale for use of broad and targeted immunotherapies for severe COVID-19 in sub-Saharan Africa, illustrate the relevance of local viral and host factors to SARS-CoV-2 immunopathology, and highlight underemphasized yet therapeutically exploitable immune pathways driving COVID-19 severity.

The NF-κB family of transcription factors and the Ras family of small GTPases are important mediators of proproliferative signaling that drives tumorigenesis and carcinogenesis. The κB-Ras proteins were previously shown to inhibit both NF-κB and Ras activation through independent mechanisms, implicating them as tumor suppressors with potentially broad relevance to human cancers. In this study, we have used two mouse models to establish the relevance of the κB-Ras proteins for tumorigenesis. Additionally, we have utilized a pan-cancer bioinformatics analysis to explore the role of the κB-Ras proteins in human cancers. Surprisingly, we find that the genes encoding κB-Ras 1 ( NKIRAS1 ) and κB-Ras 2 ( NKIRAS2 ) are rarely down-regulated in tumor samples with oncogenic Ras mutations. Reduced expression of human NKIRAS1 alone is associated with worse prognosis in at least four cancer types and linked to a network of genes implicated in tumorigenesis. Our findings provide direct evidence that loss of NKIRAS1 in human tumors that do not carry oncogenic RAS mutations is associated with worse clinical outcomes.

In April 2023, following the annual International Committee on Taxonomy of Viruses (ICTV) ratification vote on newly proposed taxa, the phylum Negarnaviricota was amended and emended. The phylum was expanded by one new family, 14 new genera, and 140 new species. Two genera and 538 species were renamed. One species was moved, and four were abolished. This article presents the updated taxonomy of Negarnaviricota as now accepted by the ICTV.

This review provides a summary of the recently ratified changes to genus and species nomenclature within the virus family Flaviviridae along with reasons for these changes. First, it was considered that the vernacular terms “flaviviral”, “flavivirus”, and “flaviviruses” could under certain circumstances be ambiguous due to the same word stem “flavi” in the taxon names Flaviviridae and Flavivirus; these terms could either have referred to all viruses classified in the family Flaviviridae or only to viruses classified in the included genus Flavivirus. To remove this ambiguity, the genus name Flavivirus was changed to Orthoflavivirus by the International Committee on Taxonomy of Viruses (ICTV). Second, all species names in the family were changed to adhere to a newly ICTV-mandated binomial format (e.g., Orthoflavivirus zikaense, Hepacivirus hominis) similar to nomenclature conventions used for species elsewhere in biology. It is important to note, however, that virus names remain unchanged. Here we outline the revised taxonomy of the family Flaviviridae as approved by the ICTV in April 2023.

The International Committee on Taxonomy of Viruses recently adopted, and is gradually implementing, a binomial naming format for virus species. Although full Latinization of these names remains optional, a standardized nomenclature based on Latinized binomials has the advantage of comparability with all other biological taxonomies. As a language without living native speakers, Latin is more culturally neutral than many contemporary languages, and words built from Latin roots are already widely used in the language of science across the world. Conversion of established species names to Latinized binomials or creation of Latinized binomials de novo may seem daunting, but the rules for name creation are straightforward and can be implemented in a formulaic manner. Here, we describe approaches, strategies and steps for creating Latinized binomials for virus species without prior knowledge of Latin. We also discuss a novel approach to the automated generation of large batches of novel genus and species names. Importantly, conversion to a binomial format does not affect virus names, many of which are created from local languages.