ETIDIOH - NEW

  Abstract The MERS-COV virus is a zoonotic coronavirus that emerged in 2012 in KSA and caused viral illness with a case fatality rate up to 35 %. Over a decade later, the virus is still evolving and circulating . The aim of this review is to discuss the current epidemiology of MERS-COV both in humans and animals, during and post the COVID-19 pandemic. We have found that MERS-COV is still evolving in camels with new lineages being detected in Saudi Arabia . Although the number of human cases has decreased , there is a gradual resurgence in the number of cases. Furthermore, many cases are being reported without exposure to camels and/or raw products, nor contact with known human cases . This necessitates global efforts in the surveillance of asymptomatic carriers in the community, role of unknown animal reservoirs in the virus spread if any, as well as extensive genomic surveillance of the virus. This is in order to unveil and assess the genetic changes that the virus is undergoing ...

  Abstract Avian influenza H5N1 clade 2.3.4.4b viruses caused a global panzootic and, unexpectedly, widespread outbreaks in dairy cattle , therefore representing a pandemic threat . To inform control strategies, it is critical to determine whether the potential to adapt to bovine cells is a general feature of H5N1 viruses , is specific to viruses of clade 2.3.4.4b, or narrowly restricted to some genotypes within this clade. Using a large panel of recombinant viruses representing >60 years of H5N1 history and other IAVs for comparison, we demonstrate replicative fitness in bovine cells is: (i) highly variable across 2.3.4.4b genotypes, (ii) limited in viruses predating the global expansion of this clade , (iii) determined by the internal gene cassette, and (iv) not restricted to udder epithelial cells. Mutations in the PB2 polymerase subunit emerge as key determinants of adaptation , although their phenotypic effects are context dependent. Bovine B3.13 and some avian genotypes ex...

  Abstract SARS-CoV-2 rapidly adapts to new hosts following cross-species transmission; this is highly relevant as unique within-host variants have emerged following infection of susceptible wild and domestic animal species . Furthermore, SARS-CoV-2 transmission from animals (e.g., white-tailed deer, mink, domestic cats, and others) back to humans has been observed , documenting the potential of animal-derived variants to infect humans. Here, we investigate SARS-CoV-2 evolution and host-specific adaptation during an outbreak in Amur tigers (Panthera tigris altaica), African lions (Panthera leo), and spotted hyenas (Crocuta crocuta) at Denver Zoo in 2021 . SARS-CoV-2 genomes from longitudinal samples from 16 individuals are evaluated for within-host variation and genomic signatures of selection, and we determine that the outbreak was likely initiated by a single spillover of a rare Delta sublineage . Within-host virus populations rapidly expand and diversify, and we detect signature...

  Abstract Genomic sequencing of reemerging highly pathogenic avian influenza A(H5N1) virus detected in Argentina in February 2025 revealed novel triple-reassortant viruses containing gene segments from Eurasian H5N1 and low pathogenicity viruses from South and North American lineages . Our findings highlight continued evolution and diversification of clade 2.3.4.4b H5N1 in the Americas. Source:  Link:  https://wwwnc.cdc.gov/eid/article/31/12/25-0783_article ____

  Abstract I nterspecies transmission of human influenza A viruses (FLUAV) to swine occurs frequently, yet the molecular factors driving adaptation remain poorly understood . Here we investigated how vaccine-induced immunity shapes the evolution of a human-origin H3N2 virus in pigs using an in vivo sustained transmission model . Pigs (seeders) were vaccinated with a commercial inactivated swine vaccine and then infected with an antigenically distinct FLUAV containing human-origin HA/NA . Contact pigs were introduced two days later. After 3 days, seeder pigs were removed, and new contacts introduced. This was repeated for a total of 4 contacts. Sequencing of nasal swab samples showed the emergence of mutations clustered near the HA receptor binding site , enabling immune escape and abolishing binding to N-glycolylneuraminic acid. Mutant viruses recognized α2,6-sialosides with 3 N-acetyllactosamine repeats , which are rare in swine lungs, while the parental virus bound structures wit...

  Abstract Highly pathogenic avian influenza H5N1 rarely infects mammals. In 2024-2025, however, genotypes B3.13 and D1.1 caused two independent spillovers into U.S. dairy cattle . By analysing 26,930 complete H5N1 genomes from global surveillance , we identified 73 major viral groups , most of which show continent-specific distribution in Europe, Asia, Africa , and North America . North American viruses exhibit higher genetic diversity in specific viral segments , including variants potentially associated with mammalian adaptation . Both dairy-cattle-associated B3.13 and D1.1 genotypes originate from the same geographic macro-area , suggesting a possible regional hotspot where avian-mammalian interfaces may facilitate viral adaptation. Our findings place the U.S. outbreaks in a global framework and indicate that North American H5N1 may be predisposed to cross-species transmission. Competing Interest Statement The authors have declared no competing interest. Funder Information Decl...

  Abstract Efficient replication of influenza A viruses (IAVs) requires balanced activities of hemagglutinin (HA), neuraminidase (NA), and the RNA polymerase complex, whose functions are strongly influenced by PB2 mutations . We previously revealed three distinct evolutionary pathways for PB2 mutations, with two pathways leading to the emergence of viral strains responsible for human seasonal infections and the 2009 pandemic , and a third pathway giving rise to H5Nx highly pathogenic avian influenza viruses (HPAIVs) defined by a triad of mutations (I147T, K339T, and A588T) that occasionally spill over to humans . Here, we investigated the zoonotic risk posed by this triad and elucidated its evolutionary relationship with HA, NA, and vaccination . Recombinant PR8 and clade 2.3.2.1c H5N1 viruses carrying the triad replicated efficiently in embryonated chicken eggs and had moderate replication efficiency in mammalian cells ; moreover, mice infected with these viral strains exhibited m...

  Abstract Avian influenza viruses (AIVs) pose a significant zoonotic threat, with the emerging H3N8 subtype raising increasing concern due to sporadic human infections . Current strategies for risk assessment of novel AIVs primarily rely on genetic surveillance and isolated case reports, which provide limited insight into their cross-species transmission potential . However, these approaches may overlook critical phenotypic determinants , such as pathogenicity, transmissibility, and environmental persistence , that directly influence zoonotic risk . This study investigates the evolutionary relationships , receptor-binding properties, replication dynamics, pathogenicity in mice, transmission efficiency in guinea pigs, and environmental persistence of three H3N8 strains isolated from a live poultry market . All three H3N8 strains bound exclusively to α-2,3 sialic acid receptor and achieved 100% transmissibility among guinea pigs through direct contact . Notably, the environment-orig...

  Abstract Increase in human H5N1 spillover infections resulting from dissemination of highly pathogenic avian influenza (HPAI) virus into bird and mammal populations raises concerns about HPAI gaining human transmissibility . Studies identified hemagglutinin (HA) acid stability and receptor preference as essential traits that shape host tropism. Mutations that increase HA stability and affinity for α−2,6-linked sialic acids have been shown to confer airborne transmissibility in a ferret model , however mechanisms of activation of H5 subtype HA are poorly understood and the effect of adaptive mutations on HA function has been largely inferred from static structures. Here, we use hydrogen/deuterium-exchange mass spectrometry to dissect activation dynamics for two ancestral H5 HPAI HA , their transmission-adapted HA , and a contemporary HA . We identify variation in receptor binding site flexibility and demonstrate that adaptive mutations result in suppression of fusion peptide dynam...

  Abstract Importance Since the early 2000s, companion animals emerged as unexpected players in influenza A virus ecology . Canine influenza viruses and the increasing detection of highly pathogenic avian influenza viruses in cats have raised concerns about their potential role as intermediate hosts for pandemic emergence . Their unique position at human-animal interface creates unprecedented opportunities for viral evolution and bidirectional transmission between humans and animals. Observations This review examined the transmission pathways and molecular adaptations of influenza A virus in companion animals. Cats primarily acquire infections through alimentary routes , including consumption of raw poultry and unpasteurized milk , as well as environmental exposure through hunting. Dogs transmit influenza viruses via respiratory droplets in high-density settings such as shelters and kennels . Canine influenza viruses demonstrate successful mammalian adaptation through accumulated m...

  Abstract Highly pathogenic avian influenza (HPAI) H5 viruses have recently been documented in mammals including humans , posing a major threat to global public health . To prevent a potential H5 pandemic , it is critical to elucidate the antigenic evolutionary pattern and identify key drivers underlying its evolution . In this work, we construct a comprehensive antigenic map of H5 influenza viruses spanning their evolutionary history and classified three antigenic clusters with no cross-neutralization . The first corresponds to ancestral clades, the second to 2.3.4.4* clades being predominant since 2010, and the third to 2.3.4.4 h clade. Despite the gradually increasing genetic distances from ancestral to 2.3.4.4* to 2.3.4.4 h, their antigenic evolution does not follow the same progressive pattern: the antigenic distance between 2.3.4.4 h and ancestral is smaller than that between 2.3.4.4* and ancestral . This divergence is associated with two distinct mutation patterns at six ke...

  Abstract Three critically ill or fatal avian influenza A(H5N1) human infections have been reported in North America since November 2024 . Notably, all were infected with genotype D1.1 instead of B3.13, the dominant genotype before November 2024. Here, we demonstrated that D1.1 could replicate to higher titers in human nasal and airway organoid-derived transwell monolayers from 6 donors . D1.1 exhibited a better binding to α2,3- and α2,6-linked SA than B3.13. No significant differences in most inflammatory or antiviral cytokines/chemokines was observed. These observations suggest that D1.1 is better adapted to both the upper and lower human respiratory tract epithelium than B3.13. Source:  Link:  https://academic.oup.com/jid/advance-article/doi/10.1093/infdis/jiaf598/8341570#google_vignette ____

  Abstract The evolutionary divergence of the A(H5) hemagglutinin (HA) gene of high pathogenicity avian influenza (HPAI) viruses (A/goose/Guangdong/96 lineage) was analyzed by phylogenetic and average pairwise distance methods to identify clades that merit nomenclature updates . Based on this assessment, 12 new clade designations were recommended based on division of clade 2.3.2.1c and 2.3.4.4 viruses, which were reported in Africa, Antarctica, Asia, Europe, the Middle East, the Americas and Oceania since the most recent WHO/WOAH/FAO H5 Evolution Working Group update. Competing Interest Statement The authors have declared no competing interest. Source:  Link:  https://www.biorxiv.org/content/10.1101/2025.11.23.690055v1 ____

  Abstract Dipeptidyl peptidase-4 (DPP4) is an established receptor for Middle East respiratory syndrome-related coronaviruses (MERSr-CoVs), while recent studies have identified angiotensin-converting enzyme 2 (ACE2) usage in multiple merbecovirus clades . Yet, receptor usage of many genetically diverse bat MERSr-CoVs remains unclear . Here we show that broadly distributed HKU25 clade merbecoviruses use ACE2 , rather than DPP4, as their receptor. Cryo-electron microscopy revealed that HsItaly2011 and VsCoV-a7 strains engage ACE2 similarly to HKU5 but with remodelled interfaces and distinct orthologue selectivity, suggesting a shared evolutionary origin of ACE2 recognition . EjCoV-3, a close relative of the DPP4-using BtCoV422, showed broad multi-species ACE2 tropism and preadaptation to human ACE2 . Several ACE2 glycans and residues within or near the binding interface were identified as determinants of orthologue selectivity. These viruses remain sensitive to several broadly neutr...

  ABSTRACT Subtype H3N2 influenza A viruses (IAVs), which emerged in 1968 to cause a pandemic, have shown continual circulation and adaptation that has necessitated frequent updates of candidate vaccine viruses . Here, we sought to determine how genetic changes in the hemagglutinin (HA) and neuraminidase of 21 antigenically distinct H3N2 IAVs isolated from 1968 to 2019 correlate with mammalian fitness and adaptation. We found a surge of adaptation between 1997 and 2002 , resulting in the emergence of A/Fujian/411/2002 (H3N2) and poor vaccine efficacy , leading to an epidemic during the 2003–2004 season. This surge was characterized by a large reduction in binding to mammalian-type α2,6-linked sialic acids and increased infectivity and replication kinetics in humanized Madin-Darby canine kidney cells. HA glycosylation also increased most rapidly from 1968 to 2004 and then plateaued. Symptomatic infections were only evident in mice following inoculation with viruses isolated in the 1...

  ABSTRACT Systemic spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to extrapulmonary tissues has been observed following acute infections. Autopsy studies further indicate tissue-specific virus diversity, including in immune-privileged sites . Questions remain on the viral dynamics leading to the tissue tropism of SARS-CoV-2, including evolutionary trajectories and functional adaptations that could impact persistence and transmission . In this study, we characterized SARS-CoV-2 genomes from 27 distinct tissues collected from an autopsy case where the patient had a primary immune deficiency . We identified tissue-specific virus genotypes , in some instances coexisting within the same sites, with mutations primarily in the receptor-binding domain of the spike protein. Protein simulations and isolation of infectious virus indicate combinations of spike substitutions that would lead to increased protein stability and stronger binding of the virus to host cells. ...

  Abstract Avian influenza viruses (AIVs) are a global public health risk; human infection is typically associated with high mortality . While the relationship between several mammalian adaptive mutations and host factors have been described, it is unknown whether additional uncharacterised mutations lead to adaptation. Here, we combine phylogenetic analysis and complementary experimental methods to quantify the impact of novel mutations that emerge at the avian-mammal interface . We constructed phylogenetic trees of mammalian and avian influenza sequences for the polymerase (PA, PB1, PB2) and nucleoprotein (NP) segments and identified potential avian to mammal spillover events. We found >6500 mutations across the polymerase and NP, including known signatures of mammalian adaptation such as PB2 E627K and D701N which occurred independently in mammals 143 and 56 times respectively. We selected 95 mutations which were mostly undescribed and emerged independently multiple times in a...

  Abstract The H7N9 influenza viruses, which are capable of causing severe respiratory syndrome in humans , were first discovered to infect humans in 2013 and continue to pose a persistent public health threat . Quail has been proposed as a potential intermediate host that may facilitate the emergence of novel reassorted influenza A viruses with the capacity to infect humans across species barriers; however, information on the biological characterization of quail H7N9 remains limited. In this study, we isolated and identified an avian H7N9 influenza virus from quails , designated as A/quail/Hebei/CH06-07/2018 (H7N9) and abbreviated as CH06-07, in Hebei, China . Phylogenetic analyses revealed that both the HA gene and the NA gene of CH06-07 were clustered in the Eurasian lineage . Furthermore, CH06-07 exhibited binding affinity for both α2,3-linked and α2,6-linked sialic acid receptors and demonstrated high pathogenicity in both quails and mice . Notably, transmission studies reveal...

  Abstract SARS-like betacoronaviruses (sarbecoviruses) endemic in bats pose a significant zoonotic threat to humans . Genetic pathways associated with spillover of bat sarbecoviruses into humans are incompletely understood. We previously showed that the wild-type spike of the rhinolophid bat coronavirus SHC014-CoV has poor entry activity and uncovered two distinct genetic pathways outside the receptor-binding domain (RBD) that increased spike opening, ACE2 binding , and cell entry. Herein, we show that the widely studied bat sarbecovirus WIV1-CoV is likely a cell culture-adapted variant whose progenitor bears a spike resembling that of Rs3367-CoV, which was sequenced from the same population of rhinolophid bats as SHC014-CoV. Our findings suggest that the acquisition of a single amino-acid substitution in the ‘630-loop’ of the S1 subunit was the key spike adaptation event during the successful isolation of WIV1-CoV, and that it enhances spike opening, virus-receptor recognition, a...

  Abstract Biodiversity loss is one of the greatest challenges facing Earth today. The most direct information on species losses comes from recent extinctions . However, our understanding of these recent, human-related extinctions is incomplete across life, especially their causes and their rates and patterns among clades, across habitats and over time. Furthermore, prominent studies have extrapolated from these extinctions to suggest a current mass extinction event . Such extrapolations assume that recent extinctions predict current extinction risk and are homogeneous among groups, over time and among environments. Here, we analyse rates and patterns of recent extinctions (last 500 years). Surprisingly, past extinctions did not strongly predict current risk among groups. Extinctions varied strongly among groups , and were most frequent among molluscs and some tetrapods , and relatively rare in plants and arthropods . Extinction rates have increased over the last five centuries , b...