Genomic Characterization of a Relative of Mumps Virus in Lesser Dawn Bats of Southeast Asia.

The importance of genomic surveillance on emerging diseases continues to be highlighted with the ongoing SARS-CoV-2 pandemic. Here, we present an analysis of a new bat-borne mumps virus (MuV) in a captive colony of lesser dawn bats (Eonycteris spelaea). This report describes an investigation of MuV-specific data originally collected as part of a longitudinal virome study of apparently healthy, captive lesser dawn bats in Southeast Asia (BioProject ID PRJNA561193) which was the first report of a MuV-like virus, named dawn bat paramyxovirus (DbPV), in bats outside of Africa. More in-depth analysis of these original RNA sequences in the current report reveals that the new DbPV genome shares only 86% amino acid identity with the RNA-dependent RNA polymerase of its closest relative, the African bat-borne mumps virus (AbMuV). While there is no obvious immediate cause for concern, it is important to continue investigating and monitoring bat-borne MuVs to determine the risk of human infection.

Boosting Convolution with Efficient MLP-Permutation for Volumetric Medical Image Segmentation (preprint)

Recently, the advent of vision Transformer (ViT) has brought substantial advancements in 3D dataset benchmarks, particularly in 3D volumetric medical image segmentation (Vol-MedSeg). Concurrently, multi-layer perceptron (MLP) network has regained popularity among researchers due to their comparable results to ViT, albeit with the exclusion of the resource-intensive self-attention module. In this work, we propose a novel permutable hybrid network for Vol-MedSeg, named PHNet, which capitalizes on the strengths of both convolution neural networks (CNNs) and MLP. PHNet addresses the intrinsic isotropy problem of 3D volumetric data by employing a combination of 2D and 3D CNNs to extract local features. Besides, we propose an efficient multi-layer permute perceptron (MLPP) module that captures long-range dependence while preserving positional information. This is achieved through an axis decomposition operation that permutes the input tensor along different axes, thereby enabling the separate encoding of the positional information. Furthermore, MLPP tackles the resolution sensitivity issue of MLP in Vol-MedSeg with a token segmentation operation, which divides the feature into smaller tokens and processes them individually. Extensive experimental results validate that PHNet outperforms the state-of-the-art methods with lower computational costs on the widely-used yet challenging COVID-19-20 and Synapse benchmarks. The ablation study also demonstrates the effectiveness of PHNet in harnessing the strengths of both CNNs and MLP.

SARS-CoV-2 ORF3a inhibits cGAS-STING-mediated autophagy flux and antiviral function.

Recognizing aberrant cytoplasmic dsDNA and stimulating cGAS-STING-mediated innate immunity is essential for the host defense against viruses. Recent studies have reported that SARS-CoV-2 infection, responsible for the COVID-19 pandemic, triggers cGAS-STING activation. cGAS-STING activation can trigger IRF3-Type I interferon (IFN) and autophagy-mediated antiviral activity. Although viral evasion of STING-triggered IFN-mediated antiviral function has been well studied, studies concerning viral evasion of STING-triggered autophagy-mediated antiviral function are scarce. In the present study, we have discovered that SARS-CoV-2 ORF3a is a unique viral protein that can interact with STING and disrupt the STING-LC3 interaction, thus blocking cGAS-STING-induced autophagy but not IRF3-Type I IFN induction. This novel function of ORF3a, distinct from targeting autophagosome-lysosome fusion, is a selective inhibition of STING-triggered autophagy to facilitate viral replication. We have also found that activation of bat STING can induce autophagy and antiviral activity despite its defect in IFN induction. Furthermore, ORF3a from bat coronaviruses can block bat STING-triggered autophagy and antiviral function. Interestingly, the ability to inhibit STING-induced autophagy appears to be an acquired function of SARS-CoV-2 ORF3a, since SARS-CoV ORF3a lacks this function. Taken together, these discoveries identify ORF3a as a potential target for intervention against COVID-19.

SARS-CoV-2, HIV, and HPV: Convergent evolution of selective regulation of cGAS-STING signaling.

Recognizing aberrant cytoplasmic double-stranded DNA and stimulating innate immunity is essential for the host's defense against viruses and tumors. Cyclic GMP-AMP (cGAMP) synthase (cGAS) is a cytosolic DNA sensor that synthesizes the second messenger 2'3'-cGAMP and subsequently activates stimulator of interferon genes (STING)-mediated activation of TANK-binding kinase 1 (TBK1)/interferon regulatory factor 3 (IRF3) and the production of type I interferon (IFN-I). Both the cGAS-STING-mediated IFN-I antiviral defense and the countermeasures developed by diverse viruses have been extensively studied. However, recent studies have revealed a convergent evolutionary feature of severe acute respiratory syndrome coronavirus 2 and human immunodeficiency virus (HIV) viral proteins in terms of the selective regulation of cGAS-STING-mediated nuclear factor-κB (NF-κB) signaling without any effect on cGAS-STING-mediated TBK1/IRF3 activation and IFN production. The potential beneficial effect of this cGAS-STING-mediated, NF-κB-dependent antiviral effect, and the possible detrimental effect of IFN-I in the pathogenesis of coronavirus disease 2019 and HIV infection deserve more attention and future investigation.

DNA virus oncoprotein HPV18 E7 selectively antagonizes cGAS-STING-triggered innate immune activation.

Cellular infections by DNA viruses trigger innate immune responses mediated by DNA sensors. The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon gene (STING) signaling pathway has been identified as a DNA-sensing pathway that activates interferons in response to viral infection and, thus, mediates host defense against viruses. Previous studies have identified oncogenes E7 and E1A of the DNA tumor viruses, human papillomavirus 18 (HPV18) and adenovirus, respectively, as inhibitors of the cGAS-STING pathway. However, the function of STING in infected cells and the mechanism by which HPV18 E7 antagonizes STING-induced Interferon beta production remain unknown. We report that HPV18 E7 selectively antagonizes STING-triggered nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation but not IRF3 activation. HPV18 E7 binds to STING in a region critical for NF-κB activation and blocks the nuclear accumulation of p65. Moreover, E7 inhibition of STING-triggered NF-κB activation is related to HPV pathogenicity but not E7-Rb binding. HPV18 E7, severe acute respiratory syndrome coronavirus-2 open reading frame 3a, human immunodeficiency virus-2 viral protein X, and Kaposi's sarcoma-associated herpesvirus KSHV viral interferon regulatory factor 1 selectively inhibited STING-triggered NF-κB or IRF3 activation, suggesting a convergent evolution among these viruses toward antagonizing host innate immunity. Collectively, selective suppression of the cGAS-STING pathway by viral proteins is likely to be a key pathogenic determinant, making it a promising target for treating oncogenic virus-induced tumor diseases.

Altered gut microbiota composition in children and their caregivers infected with the SARS-CoV-2 Omicron variant.

BACKGROUND: Gut microbiota alterations have been implicated in the pathogenesis of coronavirus disease 2019 (COVID-19). This study aimed to explore gut microbiota changes in a prospective cohort of COVID-19 children and their asymptomatic caregivers infected with the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) Omicron variant. METHODS: A total of 186 participants, including 59 COVID-19 children, 50 asymptomatic adult caregivers, 52 healthy children (HC), and 25 healthy adults (HA), were recruited between 15 April and 31 May 2022. The gut microbiota composition was determined by 16S rRNA gene sequencing in fecal samples collected from the participants. Gut microbiota functional profiling was performed by using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) software. RESULTS: The gut microbiota analysis of beta diversity revealed that the fecal microbial community of COVID-19 children remained far distantly related to HC. The relative abundances of the phyla Actinobacteria and Firmicutes were decreased, whereas Bacteroidetes, Proteobacteria, and Verrucomicrobiota were increased in COVID-19 children. Feces from COVID-19 children exhibited notably lower abundances of the genera Blautia, Bifidobacterium, Fusicatenibacter, Streptococcus, and Romboutsia and higher abundances of the genera Prevotella, Lachnoclostridium, Escherichia-Shigella, and Bacteroides than those from HC. The enterotype distributions of COVID-19 children were characterized by a high prevalence of enterotype Bacteroides. Similar changes in gut microbiota compositions were observed in asymptomatic caregivers. Furthermore, the microbial metabolic activities of KEGG (Kyoto Encyclopedia of Genes and Genomes) and COG (cluster of orthologous groups of proteins) pathways were perturbed in feces from subjects infected with the SARS-CoV-2 Omicron variant. CONCLUSION: Our data reveal altered gut microbiota compositions in both COVID-19 children and their asymptomatic caregivers infected with the SARS-CoV-2 Omicron variant, which further implicates the critical role of gut microbiota in COVID-19 pathogenesis.

The support dilemma of stroke inpatients and family caregivers under COVID-19 prevention and control: a qualitative study in China.

China has implemented a strict isolation system in hospitals since the COVID-19 pandemic, that adversely affected the psychology of inpatients and their caregivers. Face-to-face, semi-structured interviews with 22 stroke inpatients from two municipal hospitals were conducted to explore the psychological, emotional and related support needs of stroke inpatients and their family caregivers under this environment. Results which showed that external support for stroke inpatients and their family caregivers was insufficient highlight the necessity for developing specific nursing interventions that meet the psychological and emotional needs of inpatients and the caregivers.

Phaeohyphomycosis in China.

Background: Due to more attentions paid to melanized fungi over the past few decades and under the background of the global coronavirus disease 2019 pandemic (COVID-19) the fact that the virus itself and the immunosuppressive agents such as glucocorticoids can further increase the risk of infections of deep mycoses, the number of patients with phaeohyphomycosis (PHM) has a substantial increase. Their spectrum is broad and the early diagnosis and treatments are extremely sticky. This study aims to more comprehensively understand the clinical features of phaeohyphomycosis in China over 35 years and to establish a more applicable systematical classification and severity grades of lesions to guide treatments and prognosis. Methods: We reviewed 174 cases of proven phaeohyphomycosis reported in Chinese and English language literature from 1987 to 2021 and we also made the accurate classification definitions and detailed information about the epidemiology, species of clinical dematiaceous fungi, minimum inhibitory concentration values, clinical features, treatments, and prognosis. Results: The mortality of cerebral, disseminated and pulmonary phaeohyphomycosis are 55%, 36%, and 25%. Nearly 19% of patients had poor quality of life caused by the complications such as disability, disfigurements, and blindness. The overall misdiagnosis rate of phaeohyphomycosis was 74%. Moderate to severe rashes are accounting for 82% of subcutaneous phaeohyphomycosis. The areas of the head and face are mostly affected accounting for 16% of severe rashes. Nearly 30% of invasive infections of phaeohyphomycosis are triggered by recurrent lesions. Voriconazole, itraconazole, amphotericin B deoxycholate (AmB-DOC), and terbinafine were most commonly used but diagnosis and treatments of phaeohyphomycosis remain challenging in reality. Conclusions: Our classifications are likely to be more practical and easier to popularize, and there are still also plenty of characteristics in these non-specific lesions. There're no significant variations in cure rates, or death rates between three grades of lesions. But patients with severe rashes have longer courses and lower effective rates.

New-onset COVID-19-related diabetes: an early indicator of multi-organ injury and mortally of SARS-CoV-2 infection.

Objective: The pandemic of 2019 coronavirus (SARS-CoV-2) disease (COVID-19) has imposed a severe public health burden worldwide. Most patients with COVID-19 were mild. Severe patients progressed rapidly to critical condition including acute respiratory distress syndrome (ARDS), multi-organ failure and even death. This study aims to find early multi-organ injury indicators and blood glucose for predicting mortality of COVID-19. Methods: Fasting blood glucose (FBG) ≥7.0 mmol/L for two times during hospitalization and without a history of diabetes were defined as new-onset COVID-19-related diabetes (CRD). Indicators of injuries for multiple organs, including the lung, heart, kidney and liver, and glucose homeostasis were specifically analyzed for predicting death. Results: A total of 120 patients with a severity equal to or greater than Moderate were hospitalized. After excluding patients with history of diabetes, chronic heart, kidney, and liver disease, 69 patients were included in the final analysis. Of the 69 patients, 23 were Moderate, 20 were Severe, and 26 were Critical (including 16 deceased patients). Univariable analysis indicated that CRD, lactate dehydrogenase (LDH), hydroxybutyrate dehydrogenase (HBDH), creatine kinase (CK) and creatinine (Cr) were associated with death. Multivariable analysis indicated that CRD was an independent predictor for death (HR = 3.75, 95% CI 1.26-11.15). Abnormal glucose homeostasis or CRD occurred earlier than other indicators for predicting poor outcomes. Indicators of multiple organ injury were in parallel with the expression patterns of ACE2 (the SARS-CoV-2 receptor) in different organs including pancreatic islet. Conclusions: New-onset COVID-19-related diabetes is an early indicator of multi-organ injury and predictor for poor outcomes and death in COVID-19 patients. As it is easy to perform for clinical practices and self-monitoring, glucose testing will be helpful for predicting poor outcomes to facilitate appropriate intensive care.

Insights on the potential of natural deep eutectic solvents (NADES) to fine-tune durian seed gum for use as edible food coating

Approximately 75,000 tonnes of durian seeds are disposed to the environment every year and the amount will continue to increase due to the escalating demand for durians. The long-term accumulation of the wastes will lead to destruction of the ecological environment, and the disposal requires considerable effort. In fact, valuable products including durian seed gum and flour could be processed from the discarded durian seeds and hence, they should not be regarded as wastes. At the same time, the value of food wasted every year exceeds 1 trillion USD, of which 20% is caused by storage or shelf-life issues. After the outbreak of COVID-19, consumers tend to reduce the number of trips required to get fresh foods from the markets. Eventually, storage of larger amount of foods at extended period time is crucial. Thus, safe and effective food preservation materials extracted from these biomasses could potentially help in reducing food wastes. Natural deep eutectic solvent (NADES) is a green solvent composed of primary metabolites (PRIM). When combined with gum into the form of eutectogel, the characteristics are tunable indicating that the properties of natural durian seed gum can be further improved for specific application. This paper discusses the potential of eutectogels formulated using NADES and durian seed gum for use as food coating. Since the coated gel is edible, potentially low in cost, and strongly sustainable, the food preservation period can be lengthened at higher commercial value.

Health care worker occupational experiences during the COVID-19 outbreak: A cross-sectional study.

BACKGROUND: Health care workers treating coronavirus disease 2019 (COVID-19) patients experience burnout and stress due to overwork and poor working conditions. AIM: To investigate the work experiences of frontline health care workers in Wuhan city and Qinghai province, China, during the COVID-19 outbreak. METHODS: In this cross-sectional descriptive study, a self-reported questionnaire was designed to evaluate work experiences of medical staff throughout the course of the COVID-19 pandemic. A total of 178 health care workers responded to the questionnaire between February 19 and 29, 2020. Higher questionnaire dimen-sional score confirmed dimensional advantage. RESULTS: Of all dimensions evaluated by this questionnaire, the occupational value dimension had the highest mean score of 2.61 (0.59), followed by the support/security dimension score of 2.30 (0.74). Occupational protection scored lowest at 1.44 (0.75), followed by work environment at 1.97 (0.81). The social relationships dimension had an intermediate score of 2.06 (0.80). Significant differences in working conditions were observed across hospital departments, with the fever ward scoring lowest. Total scores also differed significantly across workplaces; the fever outpatient department scored lowest (P < 0.01). This phenomenon was likely due to the fact that work in the fever outpatient department, where many patients present to hospital, necessitates constant contact with a large number of individuals with insufficient provision of resources (such as protective equipment and social support). Medical workers in the fever outpatient department were burdened with a fear of COVID-19 infection and a lower sense of professional value as compared to workers in other hospital departments. Medical staff in Wuhan worked longer hours (P < 0.01) as compared to elsewhere. The mean support/security dimension score was higher for tertiary hospital as compared to secondary hospital medical staff as well as for Wuhan area as compared to Qinghai region staff (P < 0.01). Staff in Wuhan had a lower mean work environment score as compared to staff in Qinghai (P < 0.05). CONCLUSION: Medical staff treating COVID-19 patients in China report poor occupational experiences strongly affected by work environment, occupational protection and social relationships. Health care managers must address the occupational needs of medical staff by ensuring a supportive and safe work environment.

Prolonged fecal shedding of SARS-CoV-2 in a young immunocompetent COVID-19 patient: A case report and literature overview.

Clinicians are facing several challenges in tackling coronavirus disease 2019 (COVID-19); one issue is prolonged detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA. Here, we describe a case of SARS-CoV-2 infection in a young immunocompetent patient with a virological course lasting for 71 days. Following antiviral treatment, but no additional glucocorticoid or interferon therapy, the patient recovered from COVID-19 pneumonia (moderate). Detection of viral RNA via throat swabs showed negative results. However, the viral RNA reappeared and persisted in stool samples for an additional 27 days, while the patient remained asymptomatic and exhibited no abnormal signs. This case indicates that SARS-CoV-2 can result in a prolonged fecal RNA shedding, even in an immunocompetent patient with zero exposure to immunosuppressive therapies.

Response time analysis of a manufacturing supply chain with performance evaluation process algebra

The supply and demand shocks brought on by the Covid-19 crisis are forcing manufacturers everywhere to reassess or even reorganise their supply chains. This paper proposes a general framework that can achieve fast compositional modelling with stochastic performance evaluation process algebra (PEPA) for supply chain systems. The key feature of such a framework is the PEPA-based quantitative analysis approach which includes a new method for calculating response time based on compositional PEPA models. The framework aims to provide an efficient modelling prototype for supply chain systems while supporting accurate response time-based quantitative analysis. To our knowledge, this is the first work using process algebra-based compositional modelling to quantitatively analyse supply chain systems.

Presence of Recombinant Bat Coronavirus GCCDC1 in Cambodian Bats.

Bats have been recognized as an exceptional viral reservoir, especially for coronaviruses. At least three bat zoonotic coronaviruses (SARS-CoV, MERS-CoV and SARS-CoV-2) have been shown to cause severe diseases in humans and it is expected more will emerge. One of the major features of CoVs is that they are all highly prone to recombination. An extreme example is the insertion of the P10 gene from reoviruses in the bat CoV GCCDC1, first discovered in Rousettus leschenaultii bats in China. Here, we report the detection of GCCDC1 in four different bat species (Eonycteris spelaea, Cynopterus sphinx, Rhinolophus shameli and Rousettus sp.) in Cambodia. This finding demonstrates a much broader geographic and bat species range for this virus and indicates common cross-species transmission. Interestingly, one of the bat samples showed a co-infection with an Alpha CoV most closely related to RsYN14, a virus recently discovered in the same genus (Rhinolophus) of bat in Yunnan, China, 2020. Taken together, our latest findings highlight the need to conduct active surveillance in bats to assess the risk of emerging CoVs, especially in Southeast Asia.

Severity Assessment and Progression Prediction of COVID-19 Patients Based on the LesionEncoder Framework and Chest CT

Automatic severity assessment and progression prediction can facilitate admission, triage, and referral of COVID-19 patients. This study aims to explore the potential use of lung lesion features in the management of COVID-19, based on the assumption that lesion features may carry important diagnostic and prognostic information for quantifying infection severity and forecasting disease progression. A novel LesionEncoder framework is proposed to detect lesions in chest CT scans and to encode lesion features for automatic severity assessment and progression prediction. The LesionEncoder framework consists of a U-Net module for detecting lesions and extracting features from individual CT slices, and a recurrent neural network (RNN) module for learning the relationship between feature vectors and collectively classifying the sequence of feature vectors. Chest CT scans of two cohorts of COVID-19 patients from two hospitals in China were used for training and testing the proposed framework. When applied to assessing severity, this framework outperformed baseline methods achieving a sensitivity of 0.818, specificity of 0.952, accuracy of 0.940, and AUC of 0.903. It also outperformed the other tested methods in disease progression prediction with a sensitivity of 0.667, specificity of 0.838, accuracy of 0.829, and AUC of 0.736. The LesionEncoder framework demonstrates a strong potential for clinical application in current COVID-19 management, particularly in automatic severity assessment of COVID-19 patients. This framework also has a potential for other lesion-focused medical image analyses.

Outcomes of atrial fibrillation in patients with COVID-19 pneumonia: A systematic review and meta-analysis.

BACKGROUND: Recently, emerging evidence has suggested that atrial fibrillation (AF) has an epidemiological correlation with coronavirus disease 2019 (COVID-19). However, the clinical outcomes of AF in COVID-19 remain inconsistent and inconclusive. The aim of this study was to provide a comprehensive description of the impact of AF on the prognosis of patients with COVID-19 pneumonia. METHODS: Three electronic databases (PubMed, Embase, and Web of Science) were searched for eligible studies as of March 1, 2021. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the associations between AF (preexisting and new-onset) and in-hospital mortality, post-discharge mortality, and ventilator use. RESULTS: A total of 36 individual studies were incorporated into our meta-analysis. The combined results revealed that preexisting AF was associated with increased in-hospital mortality (pooled OR: 2.07; 95% CI: 1.60-2.67; p < 0.001), post-discharge mortality (pooled OR: 2.69; 95% CI: 1.24-5.83; p < 0.05), and ventilator utilization (pooled OR: 4.53; 95% CI: 1.33-15.38; p < 0.05) in patients with COVID-19. In addition, our data demonstrated that new-onset AF during severe acute respiratory syndrome coronavirus 2 infection was significantly correlated with increased mortality (pooled OR: 2.38; 95% CI: 2.04-2.77; p < 0.001). CONCLUSIONS: The presence of AF is correlated with adverse outcomes in patients with COVID-19 pneumonia, which deserves increased attention and should be managed appropriately to prevent adverse outcomes.

Orthogonal genome-wide screens of bat cells identify MTHFD1 as a target of broad antiviral therapy.

Bats are responsible for the zoonotic transmission of several major viral diseases, including those leading to the 2003 SARS outbreak and likely the ongoing COVID-19 pandemic. While comparative genomics studies have revealed characteristic adaptations of the bat innate immune system, functional genomic studies are urgently needed to provide a foundation for the molecular dissection of the viral tolerance in bats. Here we report the establishment of genome-wide RNA interference (RNAi) and CRISPR libraries for the screening of the model megabat, Pteropus alecto. We used the complementary RNAi and CRISPR libraries to interrogate P. alecto cells for infection with two different viruses: mumps virus and influenza A virus, respectively. Independent screening results converged on the endocytosis pathway and the protein secretory pathway as required for both viral infections. Additionally, we revealed a general dependence of the C1-tetrahydrofolate synthase gene, MTHFD1, for viral replication in bat cells and human cells. The MTHFD1 inhibitor, carolacton, potently blocked replication of several RNA viruses, including SARS-CoV-2. We also discovered that bats have lower expression levels of MTHFD1 than humans. Our studies provide a resource for systematic inquiry into the genetic underpinnings of bat biology and a potential target for developing broad-spectrum antiviral therapy.

HA of H1N1 enhanced the expression of ICAM-1 and IL-6 in HUVECs and pathological injury in the lungs in mice.

OBJECTIVE: Both COVID-19 and influenza are viral respiratory tract infections and the epidemics of viral respiratory tract infections remain highly prevalent with lethal consequences in susceptible individuals. Expression of ICAM-1 on vascular endothelium recruits leukocytes which initiates inflammation. IL-6 induces ICAM-1. Both ICAM-1 and IL-6 can be enhanced in influenza virus infection and COVID-19 patients. Besides initiation of virus entry host cells, whether HA alone, instead of whole virus, of influenza has the effects on expression of ICAM-1 and IL-6 in vascular endothelium with injury in the lungs, remains to be demonstrated. METHODS: RT-qPCR and Western blot as well as histopathologic examination were used to examine mRNA and protein of ICAM-1 and IL-6 as well as pathological injury in the lung tissues, respectively. RESULTS: After incubation of the Human Umbilical Vein Endothelial Cells (HUVECs) with HA of H1N1 for 24 h, the mRNA and protein of ICAM-1 and IL-6 in HUVECs were increased in group of 5 µg/ml concentration with statistical significance (p < 0.05). Pathological injury in lung tissues of the mice was shown 12 h after tail intravenous injection with 100 µl of HA (50 µg/ml and 100 µg/ml in normal saline), including widened alveolar spaces with angiotelectasis in alveolar wall, alveolar luminal and interstitial inflammatory infiltrates, alveolar luminal erythrocyte effusion. CONCLUSIONS: HA alone, instead of whole H1N1 virus, induced more expression of ICAM-1 and IL-6, two molecules involving in pathological and inflammatory responses, in HUVECs and pathological injury in lung tissues of the mice. This knowledge provides a new HA-targeted potential direction for prevention and treatment of disease related to H1N1 infection.