- Volume 106, Issue 6, 2025

Avian influenza viruses can cause severe disease when they spill over into mammalian and human hosts. H5N1 clade 2.3.4.4b has spread globally since 2021, decimating avian species, and has spilled over into mammalian species, causing sporadic infections and fatal outbreaks in sea lions, cats, mink and dairy cattle. Increased human cases of H5N1 are fuelling concern that H5N1 could soon adapt to become a new pandemic virus. Adaptive mutations have emerged following spillover, which support H5N1 outbreaks in mammalian populations and include changes to the PB2 such as E627K, D701N, M631L and T271A. Further changes to haemagglutinin, altering binding preference to human-like α2,6 sialic acid receptors have yet to be seen. Here, we review the adaptations that have emerged in mammals throughout the 2.3.4.4b outbreak and the molecular mechanisms behind these mutations to assess the pandemic risk of this virus.

Norovirus is a major cause of acute gastroenteritis in all age groups, with recent surges of cases in Europe and the USA reinforcing the influence of this virus on human health. Despite its societal impact, no vaccine or antiviral drug is available. The development of these countermeasures has been impaired at least in part by the extreme genetic and antigenic diversity of noroviruses. Here, we reviewed historical norovirus outbreaks, including the pandemics of GII.4 norovirus that were first documented in the mid-1990s, sporadic increases of non-GII.4 norovirus (e.g. GII.17 and GII.2) during the 2010s and, most recently, the ongoing large outbreaks caused by a new cluster of GII.17 noroviruses. This five-decade-long journey of tracking noroviruses in the human population illustrates the importance and challenges of battling this evolving virus.

Tembusu virus (TMUV) is an emerging mosquito-borne flavivirus, primarily transmitted by Culex spp. mosquitoes. The 2010 outbreak of TMUV in ducks revealed that the virus had acquired direct contact and aerosol transmission routes, enabling its rapid spread in duck farms. Recently, cluster 3 TMUV has increasingly been isolated from chickens, ducks and geese. In this study, we examined the pathogenicity and transmission routes of the cluster 3 TMUV Shandong 2021 (SD) strain in ducks and chickens. Our results show that TMUV SD can infect both species, but only in ducks could TMUV be detected in throat and cloacal swabs. In ducks, the virus can spread without mosquito involvement to co-housed naïve birds, demonstrating direct transmission capability. Conversely, no virus shedding and direct transmission were observed in chickens, suggesting that mosquitoes are required for virus transmission between chickens. Indeed, Culex pipiens mosquitoes could become infected by biting chickens infected with the TMUV SD and transmit the virus to naïve chickens. Our results, for the first time, provide direct evidence that TMUV can be transmitted by mosquitoes in a laboratory setting. Furthermore, our findings indicate that viral excretion through the respiratory tract and/or digestive tract is essential for direct contact transmission of TMUV, which is a critical factor in the epidemic spread of TMUV. These insights into the transmission dynamics of a cluster 3 TMUV emphasize the importance of effective vector control and biosecurity measures in managing and preventing outbreaks.

Group A rotavirus (RVA) infections are a leading cause of neonatal diarrhoea in foals. Neonatal mice could serve as a useful tool to study the pathogenesis of equine RVA (ERVA) as well as a preclinical model for assessment of vaccine efficacy. This study aimed to comparatively evaluate the clinical, virological and pathological features of ERVA G3P[12] and G14P[12] infection in neonatal mice and compare them with porcine OSU G5P[7] and bovine UK G6P[5] RVA reference strains. Neonatal mice orally inoculated with equine, bovine and porcine RVA developed short-lived diarrhoea at variable rates, G14P[12] (61%) and G3P[12] (88%). Viral replication kinetics for all strains were characterized by a gradual decline in viral load to levels below the limit of detection by 72–96 h post-infection (hpi), in line with the reduction in the number of infected enterocytes demonstrated via RNAscope® in situ hybridization. Importantly, the clinical and viral replication kinetics correlated with significant microscopic intestinal alterations characterized by enterocyte vacuolation, scalloping and hyperplasia with a peak occurring at 48 hpi and persisting until at least 96 hpi. Overall, neonatal mice develop a disease phenotype of short duration following infection with equine, porcine and bovine RVA strains characterized by diarrhoea and pronounced histological alterations in the intestinal villi. The limited intestinal viral replication is likely associated with host restriction. The clinical and pathological phenotypes developed by neonatal mice following experimental infection could serve as a preclinical tool to assess vaccine efficacy and for pathogenesis studies involving RVA of equine, porcine and bovine origin.

Entry of Zaire ebolavirus (EBOV) into a host cell is a complex process requiring interactions between the viral glycoproteins (GPs) and cellular factors. These entry factors are cell-specific and can include cell surface lectins and phosphatidylserine receptors. Niemann–Pick type C1 is critical to the late stage of the entry process. Entry has been demonstrated to be enhanced by interactions between the virion and surface-expressed lectins, which interact with carbohydrate moieties attached to the GP. In addition, soluble lectins, including mannose-binding lectin, can enhance entry in vitro. However, the mechanism of lectin-mediated enhancement remains to be defined. This study investigated the possibility that plant lectins, Wisteria floribunda agglutinin (WFA), soybean agglutinin (SBA) and Galanthus nivalis agglutinin (GNA), which possess different carbohydrate-binding specificities, influence EBOV entry. WFA was observed to potently enhance entry of lentiviral pseudotype viruses (PVs) expressing the GP of three Ebolavirus species [Zaire, Sudan (Sudan ebolavirus) and Reston (Reston ebolavirus)], with the greatest impact on EBOV. SBA had a modest enhancing effect on entry that was specific to EBOV, whilst GNA had no impact on the entry of any of the Ebolavirus species. None of the lectins enhanced the entry of control PVs expressing the surface proteins of other RNA viruses tested. WFA was demonstrated to bind directly with the EBOV-GP via the glycans, and mutational analysis implicated N238 as contributing to the interaction. Furthermore, enhancement was observed in both human and bat cell lines, indicating a highly conserved mechanism of action. We conclude that the binding of WFA to EBOV-GP through interactions including the glycan at N238 results in GP alterations that enhance entry, providing evidence of a mechanism for lectin-mediated virus entry enhancement. Targeting lectin-ligand interactions presents a potential strategy for restricting Ebolavirus entry.

Aedes aegypti is the primary vector for the transmission of dengue virus (DENV), Zika virus (ZIKV), and chikungunya virus (CHIKV). While Burkina Faso has been facing an increase in DENV epidemics, no ZIKV or CHIKV outbreaks have been reported. Here, we, therefore, assessed the vector competence of Ae. aegypti mosquitoes from Burkina Faso for ZIKV and CHIKV transmission. Ae. aegypti mosquitoes from urban and peri-urban sites of Ouagadougou were orally infected via blood meal with different titres of a West African CHIKV strain and ZIKV strains of the Asian and African lineage. The infection rate for mosquitoes from both sites was ~65% for CHIKV, whereas the dissemination was 85% and 45%, respectively, in urban and peri-urban mosquitoes. The CHIKV transmission rates ranged between 14 and 18%. For the African lineage of ZIKV, the infection rate was higher for urban mosquitoes than peri-urban mosquitoes (100% vs. 80%), whereas the dissemination rate was 100% in mosquitoes from both sites. The transmission rates for African ZIKV ranged between 12 and 18% for both urban and peri-urban mosquitoes. In contrast to ZIKV of the African lineage, low infection rates (10–30%) and dissemination rates (14–50%) were observed with the Asian lineage of ZIKV. Additionally, mosquitoes from both sites could not transmit the ZIKV strain of the Asian lineage. This study demonstrates, for the first time, the capability of Ae. aegypti mosquitoes from Burkina Faso to transmit chikungunya virus and the pre-epidemic strain of Zika virus in their saliva, highlighting the importance of establishing surveillance for these viruses in Burkina Faso.