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Two different forms of Ebola glycoprotein mediate viral entry into endotheiial cells and block activation of neutrophils resulting in hemorrhage and an impaired immune response.

Intranasal inoculation of BALB/c and C57BL/6J mice with the bovine H5N1 clade 2.3.4.4b virus  results in rapid fatal disease characterized with high viral titers in lung and brain. Interestingly, only the C57BL/6J mice develop neurologic disease.

The Middle East respiratory syndrome coronavirus (MERS-CoV) has killed ∼50% of individuals known to be infected, making understanding its mechanisms of transmission and pathogenesis and identifying candidate treatments a high priority. Heinz Feldmann, Vincent J. Munster and Michael G. Katze and their colleagues now report that treating MERS-CoV-infected rhesus macaques with interferon-α2b and ribavirin reduced virus replication and infection severity, suggesting the potential use of this combination for the clinical treatment of infected humans.

During an ongoing Ebola virus outbreak, infection before onset of protective immunity from vaccination is a possible scenario. Here the authors show in non-human primates that vaccination shortly before treatment with a monoclonal antibody does not negatively affect effectiveness of the antibody therapy.

Concerns have been raised regarding potential increase in the virulence of the Ebola virus during the current West African outbreak. Here the authors show that the ability to inhibit interferon response, one of the aspects of Ebola virus virulence, does not differ between the prototype Mayinga and isolates from the current outbreak.

While vaccines protecting against SARS-CoV-2 infection are approved, currently, there are no drugs suitable for high-risk exposure use against SARS-CoV-2. Here, Rosenke et al. provide evidence that orally delivered MK-4482, a nucleoside analog, inhibits SARS-CoV-2 replication in the Syrian hamster model.

Here the authors show that a replicating RNA vaccine encoding the hemagglutinin (HA) of contemporary H5N1 strains confers single shot protection against lethal H5N1 challenge in mice, while an RNA encoding the HA of a historical strain H5N1 confers only partial protection.

Routes of infection with bovine highly pathogenic avian influenza virus H5N1 clade 2.3.4.4b in cynomolgus macaques are investigated, and in contrast to orogastric inoculation, intranasal or intratracheal inoculation could cause systemic infection resulting in mild and severe respiratory disease, respectively.

The efficacy of T-cell-based cancer immunotherapies can be compromised by T cell exhaustion. Here the authors develop a human ex vivo exhaustion model and, based on a CRISPR-Cas9 screen, identify SNX9 as a regulator of T cell exhaustion, showing that SNX9 knockout is associated with improved T cell function and anti-tumor activity in preclinical cancer models.

A DNA-based vaccine elicits humoral and cellular immunity and provides protection against Crimean-Congo haemorrhagic fever virus-mediated disease in a non-human primate model.

Non-neutralizing antibodies against the nucleoprotein (NP) of Crimean-Congo hemorrhagic fever virus are protective against lethal challenge in mice. Here, the authors show that these anti-NP antibodies protect through the intracellular antibody receptor TRIM21 and that protection is independent of T cells.

Comparing infection routes and subsequent transmission of MPXV in the multimammate rat (Mastomys natalensis) indicates increased susceptibility, shedding and transmission via the genital mucosae.

Laboratory and clinical strains of Crimean–Congo haemorrhagic fever virus use LDLR to bind and enter host cells in blood vessel organoids and mice. Infection can also occur through ApoE, possibly present on virus particles.

Host factors involved in filovirus infection are incompletely understood. Here, the authors used a haploid cell screening system to unveil CCZ1’s crucial role in regulating endosomal trafficking thus virus movement within cells and thereby impacting Marburg and Ebola infection.

This study describes the development of a primate model for Crimean–Congo haemorrhagic fever, the first immunocompetent animal model, which will be instrumental in developing and testing medical countermeasures for this serious disease.

Crimean–Congo haemorrhagic fever (CCHF) is a severe and often lethal tick-borne illness that is caused by infection with the CCHF virus (CCHFV). In this Review, Hawman and Feldmann explore recent insights into the function of viral proteins in CCHFV pathogenesis, our current understanding of CCHF and the state of treatments and vaccines for CCHFV.

Concern over Ebola becoming endemic in West Africa has appeared in the medical and lay media. Routes of transmission, rates of viral evolution, suitability of humans as hosts and rarity of spillover events make this very unlikely. Without evidence that endemic Ebola is likely, ending epidemics should remain the focus.

Andrade, Cashman et al. evaluate varying immunization regimens of INO-4500, a DNA-based vaccine for Lassa fever, in non-human primates. INO-4500 induces humoral and cellular immune responses, conferring short- and long-term protection from lethal Lassa Virus challenge.

In this Review, Hoenen, Groseth and Feldmann address strategies that have shown promise in interfering with the filovirus life cycle, including the entry process, viral RNA synthesis and gene expression, as well as morphogenesis and budding.

Severe haemorrhagic fever is a feature of infection with both Ebola and Lassa viruses, but differences in the immune responses induced by infection in each case may have important implications for the development of specific therapies and vaccines.

Efforts towards developing post-exposure therapies for infections with filoviruses, particularly Ebola and Marburg viruses, increased substantially during the Ebola virus outbreak of 2013–2016. Geisbert and colleagues review the progress made on this front and discuss the challenges and opportunities for developing post-exposure therapies in the future.

In a recent study published in Nature, Warren et al. describe the generation of a novel synthetic adenosine analogue, BCX4430, a synthetic drug-like small molecule that provides protection from Ebola and Marburg virus infection in animal models.