Recent outbreaks of Ebola virus (EBOV) and SARS-CoV-2 have exposed our limited therapeutic options and poor understanding of cellular mechanisms that block viral infections. Using a transposon-mediated gene-activation screen in human cells, we identify that the MHC class II transactivator (CIITA) has antiviral activity against EBOV. CIITA induces resistance by activating expression of the p41 isoform of invariant chain CD74, which inhibits viral entry by blocking cathepsin-mediated processing of the Ebola glycoprotein (EboGP). We further show that CD74 p41 can block the endosomal entry pathway of coronaviruses, including SARS-CoV-2. These data therefore implicate CIITA and CD74 in host defense against a range of viruses, and identify an additional function of these proteins beyond their canonical roles in antigen presentation.

Contrary to dogma, evolutionarily young and dynamic genes can encode essential functions. We find that evolutionarily dynamic ZAD-ZNF genes, which encode the most abundant class of insect transcription factors, are more likely to encode essential functions in Drosophila melanogaster than ancient, conserved ZAD-ZNF genes. We focus on the Nicknack ZAD-ZNF gene, which is evolutionarily young, poorly retained in Drosophila species, and evolves under strong positive selection. Yet we find that it is necessary for larval development in D. melanogaster. We show that Nicknack encodes a heterochromatin-localizing protein like its paralog Oddjob, also an evolutionarily dynamic yet essential ZAD-ZNF gene. We find that the divergent D. simulans Nicknack protein can still localize to D. melanogaster heterochromatin and rescue viability of female but not male Nicknack-null D. melanogaster. Our findings suggest that innovation for rapidly changing heterochromatin functions might generally explain the essentiality of many evolutionarily dynamic ZAD-ZNF genes in insects.

Background:Two million people in the UK had a cancer diagnosis at the end of 2008. Understanding the number of people diagnosed with cancer with and without health needs is valuable information that can be used to inform service planning, treatment provision and support for people at the right time in the right place as demand grows over time.Methods:Using available data and clinically led assumptions about patient need and outcomes, we make indicative estimates. We quantify, for three common cancers, the number of people in each of the five main identified phases of the cancer care pathway.Results:Estimates are provided for each phase of the pathway for breast, colorectal and lung cancers. We estimate that there are nearly 575 000 women a year with breast cancer in the care pathway at some point in the year, 8% are in the rehabilitation phase and 4% in the progressive illness phase. This compares to nearly 270 000 with colorectal and around 95 000 with lung cancer.Conclusion:Using readily available data, we estimate the numbers of patients with different health needs. These numbers could inform the targeting of resources for service providers.

ObjectivesThe aim of this study is to categorise cancers into broad groups based on clusters of common treatment aims, experiences and outcomes to provide a numerical framework for understanding the services required to meet the needs of people with different cancers. This framework will enable a high-level overview of care and support requirements for the whole cancer population.Setting and participantsPeople in the UK with 1 of 20 common cancers; an estimated 309 000 diagnoses in 2014, 1 679 000 people diagnosed in a 20-year period and still living in 2010 and 135 000 cancer deaths in 2014.Primary and secondary outcome measuresSurvival and stage at diagnosis data were reviewed alongside clinically led assumptions to identify commonalities and cluster cancer types into three groups. The three cancer groups were then described using incidence, prevalence and mortality data collected and reported by UK cancer registries. This was then reviewed, validated and refined following consultation.ResultsGroup 1 includes cancers with the highest survival; 5-year survival is over 80%. Group 3 cancers have shorter term survival. Five-year survival is not >20% for any cancer in this group and many do not survive over a year. Group 2 includes cancers where people typically live more than a year but are less likely to live >5 years. We estimate that the majority (64%) of people living with cancer (20 year prevalence) have a cancer type in group 1 ‘longer term survival’, but significant minorities of people have cancers in group 2 ‘intermediate survival’ (19%) and group 3 ‘shorter term survival’ (10%).ConclusionsEvery person with cancer has unique needs shaped by a multitude of factors including comorbidities, treatment regimens, patient preferences, needs, attitudes and behaviours. However, to deliver personalised care, there needs to be a high-level view of potential care requirements to support service planning.

In most eukaryotes, centromeric histone (CenH3) proteins mediate mitosis and meiosis and ensure epigenetic inheritance of centromere identity. We hypothesized that disparate chromatin environments in soma versus germline might impose divergent functional requirements on single CenH3 genes, which could be ameliorated by gene duplications and subsequent specialization. Here, we analyzed the cytological localization of two recently identified CenH3 paralogs, Cid1 and Cid5, in Drosophila virilis using specific antibodies and epitope-tagged transgenic strains. We find that only ancestral Cid1 is present in somatic cells, whereas both Cid1 and Cid5 are expressed in testes and ovaries. However, Cid1 is lost in male meiosis but retained throughout oogenesis, whereas Cid5 is lost during female meiosis but retained in mature sperm. Following fertilization, only Cid1 is detectable in the early embryo, suggesting that maternally deposited Cid1 is rapidly loaded onto paternal centromeres during the protamine-to-histone transition. Our studies reveal mutually exclusive gametic specialization of divergent CenH3 paralogs. Duplication and divergence might allow essential centromeric genes to resolve an intralocus conflict between maternal and paternal centromeric requirements in many animal species.