病毒学

SA

论文Science Advances·2026年10月23日

Interferon-λ signaling to maternal dendritic cells protects against congenital Zika virus infection

Interferon-λ (IFN-λ, type III IFN) mediates antiviral immunity at anatomic barriers, including the maternal-fetal interface. To investigate the effects of IFN-λ during congenital Zika virus (ZIKV) infection, we infected mice lacking the IFN-αβ receptor ( Ifnar1 −/− ) or both the IFN-αβ and IFN-λ receptors ( Ifnar1 −/− Ifnlr1 −/− ) at embryonic day 9 and found that loss of maternal IFN-λ signaling resulted in greater transplacental transmission, highlighting a protective effect of IFN-λ at the maternal-fetal interface. To investigate the spatial relationship between ZIKV infection and antiviral responses, we used HiPlex RNAscope on the entire gravid uterus and found that IFN-λ was expressed more proximal to the site of ZIKV infection in Ifnar1 −/− dams compared to Ifnar1 −/− Ifnlr1 −/− dams. We performed immunophenotyping of the placenta and uterus by flow cytometry and found a decrease in dendritic cells and natural killer (NK) cells in the uterus of Ifnar1 −/− Ifnlr1 −/− dams compared to Ifnar1 −/− dams, but NK cell depletion did not affect fetal infection. Using conditional knockout mice, we identified maternal dendritic cells as the key IFN-λ–responsive cell type mediating protection against ZIKV congenital infection. Together, our data support a model in which IFN-λ signaling to maternal dendritic cells increases dendritic cell accumulation in the uterus, which facilitates a protective antiviral response that restricts ZIKV congenital infection.

JOV

论文Journal of Virology·2026年10月20日

Changes in the translational landscape during red clover necrotic mosaic virus infection

ABSTRACT Viruses alter host gene expression to create a proviral environment, while the host simultaneously regulates gene expression to restrict viral spread. Owing to RNA viruses’ complete reliance on the host translational machinery, it is important to assess translational control during virus infection. Therefore, we used ribosome profiling (Ribo-seq) paired with RNA-seq to observe how red clover necrotic mosaic virus (RCNMV) infection of Arabidopsis plants alters cellular gene expression at the levels of mRNA abundance and translation efficiency. We determined that at 5 days post-inoculation (dpi), the translational response to RCNMV infection is enriched in genes of the innate immune system. Expression of a tumor necrosis factor receptor-associated factor (TRAF)-like protein, a regulator of development and immune response, was translationally but not transcriptionally upregulated early in systemic infection. By 8 dpi, many pathways were regulated/dysregulated, and unfolded protein response (UPR) genes were transcriptionally upregulated but with reduced translation efficiency. Ribosome profiling of RCNMV RNAs revealed (i) −1 programmed ribosomal frameshifting at 7.5%–8.0%, the first direct measurement of frameshift efficiency in infected cells for any plant virus; (ii) that coat protein is translated at extremely high efficiency, while the RNA-dependent RNA polymerase is translated least efficiently; and (iii) an unexpected extremely strong ribosomal pause site in the open reading frame that encodes the movement protein. To our knowledge, this is the first genome-wide study that assesses the translational control of gene expression in plants infected with a virus from the large and diverse Tombusviridae family. IMPORTANCE Positive-strand RNA viruses usurp the host’s translation machinery to synthesize viral proteins. Moreover, translation of host mRNAs is altered by virus infection, both as part of the host immune response and by the virus to inhibit host defenses. To assess all these changes globally, we used ribosome profiling of plants infected with a member of the large and ubiquitous Tombusviridae family. We identified key host genes and pathways that were differentially altered in translation efficiency, giving us an understanding of host responses not detectable by conventional RNA sequencing. Moreover, ribosome profiling revealed (i) the most accurate calculation of the efficiency of ribosomal frameshifting during infection for any plant virus, (ii) the extremely high level of translation of viral coat protein, and (iii) an unexpectedly strong ribosomal pause site in the movement protein gene. This work provides an understanding of a new dimension of gene expression control in plant-virus interactions.

JOV

论文Journal of Virology·2026年10月12日

Temporal dissection of hepatitis C virus and orthoflavivirus infections by continuous luminescence monitoring

ABSTRACT Virus infection is a dynamic process consisting of rapidly evolving viral and host events, yet conventional endpoint assays provide only fragmented snapshots of these processes. Here, we established a unified temporal framework for dissecting virus–host interactions by integrating continuous bioluminescence monitoring with molecular and functional analyses. Real-time monitoring of hepatitis C virus (HCV) single-round infectious particles (SRIPs) revealed a biphasic replication profile consisting of an initial transient phase, followed by replication-dependent amplification. This transition was independently validated by similar HCV RNA kinetics observed after infection with HCV SRIPs or fully infectious HCV. Extension of this approach to dengue, Zika, and yellow fever virus SRIPs demonstrated that infection kinetics are determined by virus-specific replication programs and are modulated by the combination of viral replicons/capsids and prM/E proteins. This temporal framework enabled the identification of virus–host interactions that are difficult to resolve by conventional endpoint analyses. Early-phase cytoplasmic proteomics, combined with functional screening, identified the dynein light chain component DYNLRB2 as a previously unrecognized negative regulator of early HCV infection. Continuous monitoring also distinguished phase-specific antiviral activities, revealing distinct kinetic inhibition profiles for daclatasvir, acetylsalicylic acid, and interferon-α. Furthermore, delayed activation of the ER stress sensor ATF6 was first detected 40–47 h after HCV infection, and transcriptomic analysis at reporter-defined time points characterized the accompanying transition in host gene expression. Together, our study establishes continuous temporal monitoring as a general strategy for resolving dynamic virus–host interactions and for uncovering molecular events that remain obscured by conventional endpoint analyses. IMPORTANCE Viral infection is a dynamic process in which entry, genome amplification, host-factor requirements, antiviral effects, and cellular responses occur on different timescales. Conventional endpoint assays can identify changes in these processes but provide limited information about when they emerge or transition from one stage to another. Here, we show that continuous monitoring, when combined with direct molecular and functional measurements, can place these otherwise separate observations within a common temporal framework. Using HCV and related orthoflavivirus SRIPs, we resolved early and replication-associated phases, identified host factors with stage-dependent effects, and distinguished profiles of antiviral inhibition. We further showed that ATF6-mediated ER stress activation emerged later than early HCV infection and viral RNA amplification. Thus, continuous temporal monitoring provides a general strategy for resolving dynamic virus–host interactions by defining the temporal relationships among viral processes, pharmacological effects, and host responses that remain obscured by conventional endpoint analyses.

JOV

论文Journal of Virology·2026年10月6日

Infection and transmission dynamics of bovine and human influenza A H5N1 viruses in mouse and hamster models

ABSTRACT Here we investigated the pathogenesis and contact transmission of bovine- and human-derived highly pathogenic avian influenza (HPAI) H5N1 clade 2.3.4.4b genotype B3.13 viruses in mammalian models. Using reverse genetics, we rescued three naturally occurring viruses, rTX2/24 (bovine-derived), rTexas/37, and rMichigan/90 (both human-derived), and compared their infection dynamics, replication, and pathogenicity with the wild-type bovine TX2/24 strain in vitro and in vivo . All four viruses demonstrated comparable replication kinetics in four mammalian cell lines. However, the rMichigan/90 strain exhibited smaller plaques in bovine and human cells. In vivo studies showed that mice infected with any of the viruses succumbed to infection within 4–5 days; however, mice infected with the rMichigan/90 virus exhibited slightly lower viral replication and shedding compared with the other strains. The hamster model showed a milder infection phenotype than mice in which all viruses induced body weight loss and oral shedding, with robust virus replication observed in tissues, but the rMichigan/90 virus presented reduced replication and shedding. Contact transmission studies in hamsters revealed limited transmissibility for these viruses, with only one out of four animals inoculated with the rMichigan/90 virus transmitting it to a naïve contact. These findings indicate that both bovine- and human-derived H5N1 genotype B3.13 viruses present high pathogenicity in rodent models, though the overall respiratory transmissibility remains low in the hamster model. IMPORTANCE Influenza A H5N1 virus spilled over from wild birds into dairy cattle in the United States in 2024. Since then, an increased number of human infections—with at least 71 confirmed cases—have been confirmed. In the present study, we evaluated and compared the pathogenicity and transmissibility of a bovine and two human H5N1 viruses of the genotype B3.13. Our results show that while all viruses are pathogenic in mouse and hamster models, the bovine isolate TX2/24 presents a broader tissue tropism than the human-derived viruses. Contact transmission studies revealed a limited ability of these viruses to transmit in the hamster contact transmission model. These findings highlight the high pathogenicity of H5N1 viruses in mammals and demonstrate that their respiratory transmissibility potential remains low in the hamster model.

JOV

论文Journal of Virology·2026年10月20日

Non-neutralizing antibody responses control acute Crimean-Congo hemorrhagic fever virus infection in naïve mice

ABSTRACT Crimean-Congo hemorrhagic fever virus (CCHFV) is the cause of a sometimes-severe viral hemorrhagic fever, CCHF. Severe cases of CCHF often have little-to-no CCHFV-specific antibody responses prior to death. However, it is unclear if the failure to mount an antibody response is the cause of a poor outcome or a correlate of a failed host response. Here, we used a mouse-adapted strain of CCHFV (MA-CCHFV) to investigate the requirement of humoral immunity in control of acute CCHFV infection in immunocompetent mice. We found that mice infected with MA-CCHFV develop a rapid non-neutralizing antibody response, consistent with humans infected with CCHFV. Further, we found that the absence of humoral immunity in male but not female mice resulted in near-uniform mortality. Lastly, we determined that complement but not activating Fc-receptors nor the cytoplasmic Fc-receptor tripartite motif containing protein 21 contributed to antibody-mediated control of MA-CCHFV infection. Together, our findings identify rapid humoral immune responses as a critical component of the host response to acute CCHFV infection in naive hosts. IMPORTANCE Crimean-Congo hemorrhagic fever virus (CCHFV) is the cause of a serious viral hemorrhagic fever in humans. Severe disease and poor outcomes are correlated with little-to-no CCHFV-specific antibody. However, it is unknown if the lack of CCHFV-specific antibody is a direct cause or merely a correlate of a poor outcome. Here, we investigated the contribution of humoral immunity in control of acute CCHFV infection in naive immunocompetent mice. We found that mice develop a rapid, non-neutralizing antibody response that is crucial for control of the acute infection. Further, we found that loss of complement but not activating Fc receptors or the cytoplasmic Fc receptor TRIM21 worsened disease. Together, our findings suggest that lack of CCHFV-specific antibody responses may directly contribute to poor outcomes in CCHFV-infected humans.

JOV

论文Journal of Virology·2026年10月20日

BTX-A51 treatment modulates host innate immune responses via NF-κB and β-catenin signaling during Rift Valley fever virus infection in vitro

ABSTRACT Rift Valley fever virus (RVFV) is a zoonotic and mosquito-borne hemorrhagic pathogen of high pandemic potential, endemic to most countries in Africa. It most severely causes disease in small domestic ruminants and is transmitted to humans. RVFV has been declared a priority pathogen by the World Health Organization for vaccine and therapeutic development. Outbreaks of this virus are known to cause great disturbances to the economy, agriculture, food availability, and healthcare system of local communities. No U.S. FDA-approved vaccines or therapeutics exist for the prevention or treatment of RVFV. Here, we used BTX-A51, an anticancer drug and casein kinase-1 (CK1) inhibitor, as a pharmacological tool to investigate the role of CK1 in regulating innate immune signaling during RVFV infection. The results show that CK1 inhibition via BTX-A51 dampened NF-κB-mediated signaling by blocking different steps in the cascade that require CK1 phosphorylation for signal progression. Consequently, this reduced translocation of p65 to the nucleus and transcriptional activation of pro-inflammatory cytokines and enzymes. Additionally, BTX-A51 treatment influenced the β-catenin pathway, resulting in a significant increase in β-catenin protein levels and β-catenin colocalization with p65. Delayed BTX-A51 treatment retained its impact on cytokine gene expression and partially rescued cells from RVFV-induced cell death. Our data suggest that CK1 inhibition influences both RVFV replication and host innate immune signaling, suggesting a relationship between the NF-κB and β-catenin pathways during RVFV infection. These findings identify CK1-mediated signaling as a potential target for host-directed therapeutic strategies aimed at limiting excessive virus-induced inflammation. IMPORTANCE Rift Valley fever virus (RVFV) is a zoonotic and mosquito-borne pathogen of high pandemic risk, affecting ruminants and humans. Disease outbreaks cause great health and economic disruptions to communities across the African continent, being famously known for its “abortion storms.” Casein kinase 1 (CK1) is a host kinase ubiquitously present in eukaryotic cells and involved in multiple pathways, such as NF-κB-mediated inflammation and β-catenin signaling. Both NF-κB and β-catenin signaling are altered in RVFV-infected cells. This manuscript tests the ability of BTX-A51, a CK1 inhibitor, to limit viral replication and inflammatory signaling. BTX-A51 acted concomitantly on the NF-κB and β-catenin pathways to reduce proinflammatory signaling in RVFV-infected cells. Due to many mechanisms of infection being conserved across the Bunyavirales order, these findings also create the potential for BTX-A51 treatment to be tested against different viruses as a tool for pandemic preparedness.

SA

论文Science Advances·2026年10月9日

Exposure route, not dose, is the primary driver of infection patterns for a respiratory virus

Infectious disease severity, shedding, and within-host kinetics can vary substantially with exposure dose, inoculation route, and host factors. However, the relative contributions of these variables to infection heterogeneity remain poorly quantified because small sample sizes in controlled in vivo experiments limit their statistical power and scientific scope. Here, by compiling and jointly analyzing the largest published database of nonhuman primate challenge experiments (107 studies; 721 animals), we show that exposure route drives SARS-CoV-2 infection kinetics more strongly than dose, age, sex, or species. Aerosol inoculation yields kinetics distinct from all other respiratory exposure routes. Route and dose jointly determine which tissues become infected, and 50% infectious doses vary greatly depending on the route of exposure and on the tissue sampled. Our findings underscore the central role of exposure route in pathogenesis and transmission, and highlight the untapped potential for quantitative, cross-study syntheses to extract additional insights from costly animal experiments.

SA

论文Science Advances·2026年10月9日

Influenza A virus infection induces immune dysregulation in the placenta and fetus without vertical transmission in nonhuman primates

Influenza A virus (IAV) infection during pregnancy is associated with stillbirth and preterm birth. We hypothesized that maternal IAV infection disrupts placental and fetal immune networks in ways that correlate with disease severity. Pregnant pigtail macaques were inoculated with IAV [A/California/07/2009 (H1N1)] and underwent delivery and fetal necropsy 5 days postinfection ( N = 11), with comparison to uninfected controls ( N = 16). Stillbirth occurred in 18% of infected pregnancies and in no controls. Although vertical transmission was not observed, low levels of viral RNA were detected in two placentas. Maternal infection was associated with induction of a type I interferon response in the placenta and altered innate and adaptive immune cell populations in the fetus. Maternal disease metrics (e.g., lung viral load and interferon-α) were rarely associated with placental immune perturbations but frequently linked to fetal immune cell populations (CD4 + and CD8 + T cells and monocyte subsets). Collectively, these data indicate that maternal IAV disease severity is associated with dysregulated fetal immunity.

JOV

论文Journal of Virology·2026年10月7日

Repurposing tretinoin, a vitamin A derivative, against Chikungunya virus infection

ABSTRACT Chikungunya virus (CHIKV) has reemerged as a global pathogen causing serious public health threat, particularly due to the absence of specific antivirals. Retinoids, vitamin A derivatives, have demonstrated antiviral potential against different viral infections, yet their efficacy against alphaviruses has never been investigated. In this study, tretinoin (TR), or all-trans retinoic acid (ATRA), was evaluated for its anti-CHIKV activity using in vitro , in vivo , and ex vivo models. TR abrogated CHIKV infection efficiently in Vero and C2C12 cells, with a marked reduction (>90%) in viral RNA, proteins, and progeny formation. The IC 50 of TR against CHIKV was estimated to be 20.05 µM and 19.71 µM in Vero and C2C12 cells, respectively. Additionally, TR showed remarkable virucidal activity and effective inhibition during entry, as well as in the early stages of post-CHIKV infection. Next, the global transcriptome profile demonstrated that the “signaling by retinoic acid” pathway was significantly enriched after CHIKV infection, and retinoic acid receptors (RARs), specifically RAR-β, are the key mediators for the anti-CHIKV effect of TR. Further, the drug alters phosphorylated mitogen-activated protein kinases (MAPKs), NF-κB, and proinflammatory cytokines during CHIKV infection in RAW 264.7 cells. Interestingly, TR protected C57BL/6 mice from CHIKV challenge by diminishing viral burden, leading to reduced clinical scores and better survival. Similar observations were also noticed in the ex vivo models of CHIKV-infected primary human skeletal muscle myoblasts (HSMMs). In conclusion, this work demonstrated the repurposing potential of TR against CHIKV infection for the first time, encouraging its clinical validation toward future therapeutics. IMPORTANCE Chikungunya virus (CHIKV) is an arbovirus causing Chikungunya fever (CHIKF), leading to debilitating arthralgia and myalgia. The unavailability of licensed antivirals against CHIKV encourages extensive research to find a therapeutic cure. Retinoids, the derivatives of vitamin A, have been repurposed as antiviral agents against a broad range of viruses; however, their potency against alphaviruses remains unexplored. Accordingly, tretinoin (TR), also known as all-trans retinoic acid (ATRA), was validated for anti-CHIKV efficacy in this investigation. Significant perturbations of CHIKV titer, RNA, and protein levels were observed in the presence of TR following infection, and its antiviral effect was mediated through RAR-β. Moreover, the anti-CHIKV potential of TR was evaluated in the mouse model and primary human skeletal muscle myoblasts, indicating strong preclinical efficacy. Finally, this is the first study to report the antiviral property of TR against CHIKV infection using in vitro , in vivo , and ex vivo approaches, suggesting its repurposing potential.

JOV

论文Journal of Virology·2026年10月22日

Antagonism of PRDX1 and Japanese encephalitis virus via the autophagy pathway

ABSTRACT Japanese encephalitis virus (JEV) is a mosquito-borne zoonotic infectious agent and causes animal and human illness of the central nervous system. Japanese encephalitis virus inflicts severe harm, yet even with an approved vaccine, prevention and control remain daunting, and the molecular mechanism underlying the virus-host interplay remains incompletely understood. In this study, we found that the host peroxiredoxin 1 (PRDX1) protein inhibits JEV replication. PRDX1 targets nonstructural protein 1 (NS1) of JEV and mediates its degradation via the proteasome and autophagy pathways, thus inhibiting viral replication. By targeting TRAF6, an E3 ligase, the PRDX1 protein catalyzes the ubiquitination of NS1, leading to its recognition by NDP52, a cargo receptor, along with lysosomal degradation. We also found that the JEV NS3 protein can target and degrade PRDX1 to decrease the antiviral function of PRDX1, which is a tactic by which viruses confront the host. In conclusion, these findings showed that selective autophagy has dual functions in the host and JEV: it can degrade viral proteins to inhibit viral replication and host antiviral proteins to promote viral replication. IMPORTANCE Japanese encephalitis virus (JEV) is a flavivirus capable of inducing human encephalitis and dysgenesis in gestating sows. It has an extraordinary ability to hijack cellular systems and evade defenses, establishing infection and spreading it throughout the body to cause disease. During viral infection, the host initiates several antiviral responses and activates various host-restricted factors to resist viral invasion. In this study, we identified PRDX1 as a novel host restrictor that inhibits viral multiplication by binding to TRAF6 (an E3 ubiquitin ligase) and NDP52 (a cargo receptor) to degrade nonstructural protein 1 (NS1) of JEV. We also found that JEV infection can downregulate intracellular PRDX1 expression via nonstructural protein 3 (NS3), thus promoting viral replication. These results revealed that the virus-host interaction is a complex and dynamic process in which viruses restrict and compete with each other.

JOV

论文Journal of Virology·2026年10月21日

Infection-specific long-chain fatty acid metabolism as a broad anti-enterovirus target

ABSTRACT Enteroviruses are arguably the most numerous group of viruses infecting humans. While most enterovirus infections are benign and self-resolving, their sheer number inevitably increases the chances of multiple complications. The diversity of enteroviruses means that the development of vaccines is only economically feasible against a select few, and no direct-acting or host-targeted anti-virals are approved to treat enteroviral infections, largely due to the rapid development of resistance against all experimental drugs. Here, we explored a universal property of enterovirus infection—a massive upregulation of phospholipid synthesis as a target for anti-viral interventions. The increased phospholipid synthesis consumes endogenously and exogenously derived long-chain fatty acids (LCFA). We demonstrate that polyunsaturated LCFAs can have a broad anti-enteroviral effect, affecting multiple steps of the virus life cycle. The anti-viral activity of LCFAs did not strictly depend on the degree of unsaturation or their capacity to induce lipid peroxidation, but significantly correlated with their conformation. This suggests that their incorporation into the phospholipid molecules makes the replication organelle membranes incapable of properly accommodating viral replication machinery. Accordingly, the inhibition of neutral lipid synthesis promoted LCFAs retargeting to the membranes in infected cells and increased their anti-viral potency. We show that this approach is effective against diverse enteroviruses in different cell types, including differentiated primary cells, and that attempts to establish viruses resistant to such treatment were unsuccessful. IMPORTANCE Humans are hosts to more than 300 distinct enteroviruses. Enterovirus infections can induce multiple short-term and long-term complications, including such serious conditions as paralysis, myocarditis, aseptic meningitis, and others. Yet, licensed vaccines are available only against poliovirus and enterovirus A71, and no specific anti-enterovirus drugs are approved for clinical practice. These viruses rapidly develop resistance to either virus- or host-acting experimental compounds. We explored a shared feature of enterovirus infection, a strong upregulation of phospholipid synthesis in infected cells, as a tool to control enterovirus replication. By altering the long-chain fatty acids composition available to infected cells, replication of diverse enteroviruses can be similarly suppressed, and the selection of resistant mutants was not successful. Thus, targeting infection-induced changes in cellular lipid metabolism, rather than individual viral or host factors, may offer a promising approach for controlling enterovirus infections.

SA

论文Science Advances·2026年10月9日

Long-term immunoprophylaxis by TLR9 ligand mediates macrophage-ILC cross-talk against respiratory viral infection

Rapid development of host immunity is critical during the emergence of viral outbreaks when vaccines are not yet available. Here, we demonstrate that CpG oligodeoxynucleotide-schizophyllan complex (K3-SPG) induces antigen-independent, long-term protection against lethal respiratory virus infection. A single intranasal administration successfully enhanced host resistance to infection for as long as 100 days posttreatment. Mechanistically, we observed a lung-restricted biphasic innate activation of macrophages and innate lymphoid cells. Early protection was mediated by CD11b + CD11c + macrophages (DP MΦ) and monocyte-derived interstitial macrophages (IMΦ). Late protection was mediated by innate lymphoid cells that were epigenetically reprogrammed, suggesting that two distinct innate immune subsets contribute to the maintenance of disease tolerance in the lung microenvironment. Deficiency of TLR9 or TNF-α abrogated innate activation and protective immunity. Collectively, these findings demonstrate that adjuvant-induced prophylaxis is a promising approach to enhancing host resistance against respiratory virus infection, involving the biphasic cooperation between innate immune cells in the local tissue.

SA

论文Science Advances·2026年10月9日

Herpes simplex virus pUL56 abolishes neuronal activity by removing voltage-gated ion channels from the plasma membrane

Herpes simplex virus 1 (HSV-1) infections of the central nervous system cause encephalitis and are associated with increased risk of neurodegeneration, yet the molecular consequences of lytic infection in human neurons remain incompletely defined. We map the transcriptomic, proteomic, and surface-proteome changes induced by HSV-1 across the lytic infection cycle in human induced pluripotent stem cell–derived cortical glutamatergic neurons. HSV-1 drives extensive plasma-membrane remodeling, including the removal of voltage-gated sodium, potassium, and calcium channels, resulting in a profound loss of synchronous calcium signaling. We identify the viral ubiquitin-ligase adaptor pUL56 as the principal effector of this process: pUL56-dependent degradation of ion channels abolishes coordinated calcium signaling, whereas mutation of its E3-ligase–binding motifs preserves synchrony. Furthermore, expression of pUL56 alone is sufficient to abolish neuronal electrical activity. These findings establish pUL56 as a potent viral suppressor of neuronal excitability.

SA

论文Science Advances·2026年10月23日

Opposing cell-type preferences for binding and replication shape influenza A virus infection in human airways

Influenza A viruses (IAVs) pose a threat to human health. Although receptor specificity, polymerase adaptation, and airway tropism have been studied extensively, it remains unresolved how they combine to shape tropism in airway epithelia. Here, we show that avian IAVs infect ciliated and secretory cells but preferentially bind to ciliated cells because of higher apical α2,3-linked sialic acid levels. As replication levels are comparable between cell types, this translates into overall preference for ciliated cells. Human IAVs also preferentially bind to ciliated cells despite comparable α2,6-linked sialic acid abundance. Instead, they show higher viral RNA and protein levels in secretory cells, linked to their compatibility with human ANP32 proteins and modestly higher ANP32A/B expression in this cell type, resulting in equal infection levels across cell types. Our findings redefine IAV tropism in the human airway as a stage-resolved process shaped by the interplay between apical glycans, viral binding, polymerase cofactor compatibility, and cell-type–specific replication capacity, moving beyond receptor-centric models.

EP

论文Europe PMC·2026年10月31日

Epidemiology and spillover risk of SFTSV in animals across East Asia.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick‑borne zoonosis in East Asia, yet the contribution of animals to virus maintenance and spillover remains incompletely characterized. This review synthesizes current evidence of SFTS virus (SFTSV) infection across domestic livestock, companion animals, wildlife, and captive species, focusing on host range, geographic distribution, diagnostics, and reports of viral RNA and virus isolation. Available data indicate that SFTSV exposure and infection occur across a broad range of animal hosts, supporting a multi-host ecological framework rather than a simple single-reservoir interpretation. Domestic ruminants frequently exhibit high seroprevalence and may function as sentinels of enzootic activity, while occasional virus isolation from cattle demonstrates that viable virus can be recovered from naturally infected livestock, although this does not establish reservoir or amplification competence. Companion animals are considered a potential interface for interspecies transmission, as some studies have documented severe clinical disease, high viral loads, and cat-associated human transmission events supported by varying levels of epidemiological and genomic evidence. Studies in wildlife further document exposure and natural infection across diverse taxa, although their specific roles in viral maintenance remain unresolved. Interpretation of these findings depends heavily on the diagnostic modality: serology primarily indicates prior exposure, RNA detection supports current or recent infection, and virus isolation demonstrates that viable virus was present in the sampled material. Integrating animal infection data within an ecological framework reveals major knowledge gaps related to reservoir competence, infectious shedding, phylogenetic connections among animal, tick, and human cases, and implications for prevention. The review underscores the need for One Health surveillance that incorporates clinical data from companion animals and applies evidence‑based interpretation to improve recognition of animal-human interfaces associated with potential spillover risk.