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This study identifies regulators of the RNA sensor RIG-I. Diverse processes, including the unfolded protein response, Wnt signalling and RNA metabolism, modulate this pathway. The splicing regulator KHSRP is identified as a negative regulator of RIG-I that affects influenza replication in vivo.

A human–SARS-CoV-2 protein interaction map highlights cellular processes that are hijacked by the virus and that can be targeted by existing drugs, including inhibitors of mRNA translation and predicted regulators of the sigma receptors.

Influenza A viruses continuously circulate and change in several animal hosts, and the emergence of novel strains that are capable of causing human epidemics or pandemics is a serious possibility. Here, Medina and García-Sastre discuss the importance of surveillance in identifying viruses with a potential risk to humans, and describe new developments in our understanding of viral host tropism and virulence.

Vaccination against one viral strain can result in cross-reactive antibodies against another viral strain. In this study, the vaccination of mice against the 2009 H1N1 virus is shown to protect mice from the 1918 Spanish influenza virus, which resulted in millions of deaths worldwide.

Monoclonal antibodies show great promise in treating Covid-19 patients. Here, Maisonnasse, Aldon and colleagues report pre-clinical results for COVA1-18 and demonstrate that it reduces viral infectivity in three animal models with over 95% efficacy in macaques upper respiratory tract.

Alternative splicing of influenza A virus (IAV) M transcript is regulated by hnRNP K and NS1-BP, but mechanistic details are unknown. Here, Thompson et al. show how hnRNP K and NS1-BP bind M mRNA and that these proteins regulate splicing of host transcripts in both the absence and presence of IAV infection.

Zika and Dengue virus non-structural protein 5 can antagonise STAT2 modulating the host response and this interaction is involved in determining tropism. Here the authors show mammals independently evolved resistance to flavivirus NS5 multiple times, involving complex genetic changes in STAT2 which balance viral defence whilst maintaining STAT2’s critical functions.

The 1997 flu in Hong Kong infected only 18 patients, but killed 6 of them. Now, reverse genetics experiments have pinpointed the NS1 gene as a primary culprit.

Recent work highlights the requirement for 2′-O-methylation of capped mRNA to prevent recognition by the antiviral host response.

Using a multi-OMICS approach, Haas et al identify 54 human genes and 16 host-targeting chemical compounds that regulate influenza A virus infection in lung epithelial cells, including AHNAK and COBP1 which are also essential for SARS-CoV-2 infection.

To thwart the antimicrobial responses of their hosts, pathogens have evolved diverse mechanisms, including autophagy. Knowledge of such mechanisms has now led to a pro-autophagy peptide that may be of therapeutic value. See Article p.201

Influenza A virus (IAV) infection induces transcription termination defects in host cells, an effect modulated by SUMOylation of an intrinsically disordered region of the influenza NS1 protein expressed by the 1918 pandemic IAV strain.

The 3CL protease of SARS-CoV-2 is inhibited by PF-00835231 in vitro. Here, the authors show that the prodrug PF-07304814 has broad spectrum activity, inhibiting SARS-CoV and SARS-CoV-2 in mice and its ADME and safety profile support clinical development.

This work identified immune signatures of COVID-19 including broad Interferon signatures that are unique to infants. Compared with infected adults, infants display similar Interferon signatures in monocytes but enhanced signatures in T and B cells.

Here, Rathnasinghe et al. characterize the pathogenesis of a mouse-adapted SARS-CoV-2 in infected obese and aged mice, and identify mutations that are present in SARS-CoV-2 variants of concern, associated with higher transmissibility.

A strategy exploiting species-specific miRNA expression may provide another layer of biosafety in gain-of-function influenza experiments.

A crystal structure of the Zika virus NS3 RNA helicase reveals similarities to the RNA helicase from Dengue virus, with variability in loops typically involved in binding ATP and RNA, and aids in identification of potentially druggable hotspots.

Genetic disposition can impact response to virus infection. Here, the authors used a reinfection approach with antigenically distinct SARS-CoV-2 variants Omicron and Beta and show that differences in the immune response correlate with disease outcome in mouse models with different genetic background upon reinfection.

The 2023 monkeypox outbreak was caused by a subclade IIb monkeypox virus (MPXV). Here, using advanced sequencing techniques, the authors identify variations on low-complexity regions of the MPXV genome and describe their potential as evolutionary drivers.

In addition to SARS-CoV-2, other coronaviruses also infect human, but whether consecutive infections cross-modulate the induced immune response is still unclear. Here the authors show that SARS-CoV-2 infection boosts pre-existing responses to other coronaviruses, yet such back-boosting hampers the induction of specific antibodies against SARS-CoV-2.

MHC class II proteins from humans, pigs, ducks, swans and chickens can serve as alternative receptor for virus entry of H2N2 influenza A viruses. This trait is conserved in Eurasian avian H2 IAV.

Here, Bhat et al. show that Influenza A virus mRNAs are exported from the nucleus via the nucleoporin Tpr and the mRNA export complex TREX-2. These mRNAs have low exon number, high mean exon length, and low GC content. A 45-nucleotide RNA signal can mediate export via TREX-2.

The SARS-CoV-2 Alpha variant suppresses innate immune responses more effectively than isolates of first-wave SARS-CoV-2, and this is a result of mutations outside of the spike coding region that lead to upregulation of viral innate immune antagonists.

Zika virus infection of human brain pericytes triggers maturation of an osteogenic factor, thereby resulting in osteogenic gene expression and calcification.

Here the authors show that a Newcastle disease virus based COVID-19 vaccine expressing a stabilized spike protein induces protective immunity in small animal models and reduces replication of variants of concerns. This vaccine candidate can be produced by influenza virus vaccine manufactures around the world.

A collaborative study demonstrates that, compared with previous SARS-CoV-2 variants, B.1.1.529 isolates cause less infection and disease in mice and hamsters, in agreement with preliminary data from studies in humans.

Iliev et al. report that increased Candida albicans accumulation in the mycobiota of patients with severe COVID-19 might be a contributing factor to the immunopathology of severe COVID-19 and have long-lasting effects on the hematopoietic stem cell compartment.

Influenza A virus (IAV) infection can be exacerbated by bacterial co-infections but the effect of IAV on the upper respiratory tract (URT) microbiome remains unclear. Here, the authors compare the dynamics of the UTR microbiome in IAV-infected ferrets and humans, finding similar trends at the ecosystem and individual taxon level in both hosts.

RIG-I is an RNA helicase that senses viral infections and triggers innate and adaptive immune mechanisms. Recent studies have identified RNAs bearing 5′-triphosphates as ligands of RIG-I and have suggested a mechanism for how RIG-I distinguishes viral RNA from host RNA.

The canonical BRG1/BRM-associated factor (cBAF) complex is recruited by HNF1A/B to angiotensin-converting enzyme 2 (ACE2) enhancers, promoting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Inhibition of the catalytic activity of SMARCA4 precludes ACE2 expression and reduces susceptibility to SARS-CoV-1 and major SARS-CoV-2 variants.

An uncharacterized influenza A-like virus (H17N10) has been detected in bats. Here the authors show that flu viruses containing certain H17N10 genes can infect human cells and mice, but do not exchange genes with other viruses, indicating that H17N10 transmission to humans is not very likely.

Strategies to advance T cell based immune therapies are mostly focusing on the improvement of CD8 T cell effector functions, such as cytotoxicity or recruitment to the tumor. Here authors show that by combining in situ vaccination with oncolytic Newcastle Disease Virus and Flt3L-driven dendritic cell expansion, the anti-tumor T cell response is amplified via increased antigen cross-presentation.

Viral pathogens frequently target host cell antigen-processing pathways, including MHC-I–TAP peptide transporters, to evade host immunity. Blander and colleagues describe how MHC-I molecules can still cross-present antigen by re-routing ERGIC-resident MHC molecules to phagosomal vesicles, where phagolysosomal proteases act to shape the peptide repertoire for MHC-I presentation.

Virus-induced senescence is a central pathogenic feature in COVID-19, and senolytics, which promote apoptosis of senescent cells, can reduce disease severity in hamsters,mice, as well as humans infected with SARS-CoV-2.

A distinct class of broadly neutralizing antibodies to the influenza virus target a membrane-proximal anchor epitope of the haemagglutinin stalk domain.

The authors do a CRISPR-knockout selection to investigate host factors required for influenza replication. They identified IFIT2 as being repurposed by influenza to promote replication.

Analysis of the genetic stability and replication potential of bat H18N11 influenza A viruses reveals that they are poorly adapted to ferrets and mice and that they transmit among bats only in presence of the full-length neuraminidase-like protein N11.

In a mouse model of influenza virus infection, inflammatory dendritic cells are recruited to the infected trachea. Their activation through the C-type lectin receptor SIGN-R1 stimulates recruitment of natural killer cells and contributes to the control of viral replication.

A screen of the ReFRAME library of approximately 12,000 known drugs for antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) identified several candidate compounds with suitable activities and pharmacological profiles, which could potentially expedite the deployment of therapies for coronavirus disease 2019 (COVID-19).