In 1967, the first reported filovirus hemorrhagic fever outbreak took place in Germany and the former Yugoslavia. The causative agent that was identified during this outbreak, Marburg virus, is one of the most deadly human pathogens. This article provides a comprehensive overview of our current knowledge about Marburg virus disease ranging from ecology to pathogenesis and molecular biology.

As obligate intracellular parasites, viruses expertly modify cellular processes to facilitate their replication and spread, often by encoding genes that mimic the functions of cellular proteins while lacking regulatory features that modify their activity. We show that the human cytomegalovirus UL97 protein has activities similar to cellular cyclin–cyclin-dependent kinase (CDK) complexes. UL97 phosphorylated and inactivated the retinoblastoma tumor suppressor, stimulated cell cycle progression in mammalian cells, and rescued proliferation of Saccharomyces cerevisiae lacking CDK activity. UL97 is not inhibited by the CDK inhibitor p21 and lacks amino acid residues conserved in the CDKs that permit the attenuation of kinase activity. Thus, UL97 represents a functional ortholog of cellular CDKs that is immune from normal CDK control mechanisms.

Although a well-regulated inflammatory response is a vital defense mechanism against viral infection, too much inflammation can be detrimental. Excessive inflammatory responses, which are characterized by elevated levels of a broad array of pro-inflammatory cytokines and chemokines, have been observed in a wide variety of viral diseases associated with serious morbidity and mortality. Examples of this include acute lung injury caused by infections with respiratory syncytial virus (RSV), influenza A virus (IAV), or severe acute respiratory syndrome coronavirus (SARS-CoV). Excessive inflammatory responses induced by viral infections are not restricted to the lung but can be systemic, as reported for Ebola virus (EBOV) disease and severe dengue [1-5]. The reasons leading to an unbalanced inflammatory response in certain viral infections are not well understood and are most likely multifactorial. Here, we explore the role of toll-like receptor 4 (TLR4) in the induction of damaging inflammatory responses during acute viral infections.

The CIITAdel keeps viruses at bay: A better understanding of cellular mechanisms involved in viral resistance is needed for the next generation of antiviral therapies. Bruchez et al. used a transposon-mediated gene-activation screen to search for previously unreported host restriction factors for Ebola virus (see the Perspective by Wells and Coyne). The authors found that a transcription factor, major histocompatibility complex class II transactivator (CIITA), induces resistance in human cell lines by directing the expression of the p41 isoform of the invariant chain (CD74). CD74 p41 then disrupts cathepsin-mediated Ebola glycoprotein processing, which prevents viral fusion and entry. CD74 p41 can also stymie the endosomal entry of coronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This work should inform future treatments against cathepsin-dependent viruses such as filoviruses and coronaviruses. Additionally, the screening strategy used may serve as a blueprint for uncovering resistance mechanisms against other dangerous pathogens. Science , this issue p. 241 see also p. 167