Estrogen mediates innate and adaptive immune alterations to influenza infection in pregnant mice

Pregnancy is a leading risk factor for severe complications during an influenza virus infection. Women infected during their second and third trimesters are at increased risk for severe cardiopulmonary complications, premature delivery, and death. Here, we establish a murine model of aerosolized influenza infection during pregnancy. We find significantly altered innate antiviral responses in pregnant mice, including decreased levels of IFN-β, IL-1α, and IFN-γ at early time points of infection. We also find reduced cytotoxic T cell activity and delayed viral clearance. We further demonstrate that pregnancy levels of the estrogen 17-β-estradiol are able to induce key anti-inflammatory phenotypes in immune responses to the virus independently of other hormones or pregnancy-related stressors. We conclude that elevated estrogen levels result in an attenuated anti-viral immune response, and that pregnancy-associated morbidities occur in the context of this anti-inflammatory phenotype.     

Effect of vaccination against pneumococcal infection and influenza in children with asthma

Assessment of clinical course of asthma and IgG response in children with asthma immunized with pneumococcal polysaccharide vaccine (Pneumo 23) and influenza vaccine (Vaxigrip). 78 children aged 4 - 17 years old were allocated to two groups. Children from the 1st group were immunized against pneumococcal infection and influenza; children from 2nd group were immunized against pneumococcal infection only. Rate of asthma exacerbations in the 1st group of children decreased by 1.7 times compared with the period before vaccination, whereas the same rate in the 2nd group of children decreased by 1.5 times. It was accompanied by the increase of IgG level to antigens of pneumococcalvaccine in blood, which was observed in both groups. Vaccination did not result in increase of IgE levels. Immunization of children with asthma against pneumococcal infection with polysaccharide vaccine or combined immunization against pneumococcal infection and influenza reduced rate of asthma exacerbations and led to formation of immunity to vaccine strains of Streptococcus pneumoniae. Vaccination did not lead to sensitization of children.     

Sociodemographic factors and clinical conditions associated to hospitalization in influenza A (H1N1) 2009 virus infected patients in Spain, 2009-2010

The emergence and pandemic spread of a new strain of influenza A (H1N1) virus in 2009 resulted in a serious alarm in clinical and public health services all over the world. One distinguishing feature of this new influenza pandemic was the different profile of hospitalized patients compared to those from traditional seasonal influenza infections. Our goal was to analyze sociodemographic and clinical factors associated to hospitalization following infection by influenza A(H1N1) virus. We report the results of a Spanish nationwide study with laboratory confirmed infection by the new pandemic virus in a case-control design based on hospitalized patients. The main risk factors for hospitalization of influenza A (H1N1) 2009 were determined to be obesity (BMI≥40, with an odds-ratio [OR] 14.27), hematological neoplasia (OR 10.71), chronic heart disease, COPD (OR 5.16) and neurological disease, among the clinical conditions, whereas low education level and some ethnic backgrounds (Gypsies and Amerinds) were the sociodemographic variables found associated to hospitalization. The presence of any clinical condition of moderate risk almost triples the risk of hospitalization (OR 2.88) and high risk conditions raise this value markedly (OR 6.43). The risk of hospitalization increased proportionally when for two (OR 2.08) or for three or more (OR 4.86) risk factors were simultaneously present in the same patient. These findings should be considered when a new influenza virus appears in the human population.     

Influenza vaccine effectiveness in the elderly based on administrative databases: change in immunization habit as a marker for bias

Background

Administrative databases provide efficient methods to estimate influenza vaccine effectiveness (IVE) against severe outcomes in the elderly but are prone to intractable bias. This study returns to one of the linked population databases by which IVE against hospitalization and death in the elderly was first assessed. We explore IVE across six more recent influenza seasons, including periods before, during, and after peak activity to identify potential markers for bias.

Methods and Findings

Acute respiratory hospitalization and all-cause mortality were compared between immunized/non-immunized community-dwelling seniors ≥65years through administrative databases in Manitoba, Canada between 2000-01 and 2005-06. IVE was compared during pre-season/influenza/post-season periods through logistic regression with multivariable adjustment (age/sex/income/residence/prior influenza or pneumococcal immunization/medical visits/comorbidity), stratification based on prior influenza immunization history, and propensity scores. Analysis during pre-season periods assessed baseline differences between immunized and unimmunized groups. The study population included ∼140,000 seniors, of whom 50–60% were immunized annually. Adjustment for key covariates and use of propensity scores consistently increased IVE. Estimates were paradoxically higher pre-season and for all-cause mortality vs. acute respiratory hospitalization. Stratified analysis showed that those twice consecutively and currently immunized were always at significantly lower hospitalization/mortality risk with odds ratios (OR) of 0.60 [95%CI0.48–0.75] and 0.58 [0.53–0.64] pre-season and 0.77 [0.69–0.86] and 0.71 [0.66–0.77] during influenza circulation, relative to the consistently unimmunized. Conversely, those forgoing immunization when twice previously immunized were always at significantly higher hospitalization/mortality risk with OR of 1.41 [1.14–1.73] and 2.45 [2.21–2.72] pre-season and 1.21 [1.03–1.43] and 1.78 [1.61–1.96] during influenza circulation.

Conclusions

The most pronounced IVE estimates were paradoxically observed pre-season, indicating bias tending to over-estimate vaccine protection. Change in immunization habit from that of the prior two years may be a marker for this bias in administrative data sets; however, no analytic technique explored could adjust for its influence. Improved methods to achieve valid interpretation of protection in the elderly are needed.     

Lymphotoxin-alpha-deficient mice make delayed,but effective,T and B cell responses to influenza

Lymphotoxin-alpha(-/-) (LTalpha(-/-)) mice are thought to be unable to generate effective T and B cell responses. This is attributed to the lack of lymph nodes and the disrupted splenic architecture of these mice. However, despite these defects we found that LTalpha(-/-) mice could survive infection with a virulent influenza A virus. LTalpha(-/-) mice and normal wild-type mice infected with influenza A generated similar numbers of influenza-specific CD8 T cells that were able to produce IFN-gamma and kill target cells presenting influenza peptides. Furthermore influenza-infected LTalpha(-/-) mice produced high titers of influenza-specific IgM, IgG, and IgA. However, both CD8 and B cell immune responses were delayed in LTalpha(-/-) mice by 2-3 days. The delayed cellular and humoral immune response was sufficient to mediate viral clearance in LTalpha(-/-) mice that were infected with relatively low doses of influenza virus. However, when LTalpha(-/-) mice were infected with larger doses of influenza, they succumbed to infection before the immune response was initiated. These results demonstrate that neither LTalpha nor constitutively organized lymphoid tissues, such as lymph nodes and spleen, are absolutely required for the generation of effective immunity against the respiratory virus influenza A. However, the presence of LTalpha and/or lymph nodes does accelerate the initiation of immune responses, which leads to protection from larger doses of virus.     

Outcomes of Influenza A(H1N1)pdm09 Virus Infection: Results from Two International Cohort Studies

Background

Data from prospectively planned cohort studies on risk of major clinical outcomes and prognostic factors for patients with influenza A(H1N1)pdm09 virus are limited. In 2009, in order to assess outcomes and evaluate risk factors for progression of illness, two cohort studies were initiated: FLU 002 in outpatients and FLU 003 in hospitalized patients.

Methods and Findings

Between October 2009 and December 2012, adults with influenza-like illness (ILI) were enrolled; outpatients were followed for 14 days and inpatients for 60 days. Disease progression was defined as hospitalization and/or death for outpatients, and hospitalization for >28 days, transfer to intensive care unit (ICU) if enrolled from general ward, and/or death for inpatients. Infection was confirmed by RT-PCR. 590 FLU 002 and 392 FLU 003 patients with influenza A (H1N1)pdm09 were enrolled from 81 sites in 17 countries at 2 days (IQR 1–3) and 6 days (IQR 4–10) following ILI onset, respectively. Disease progression was experienced by 29 (1 death) outpatients (5.1%; 95% CI: 3.4–7.2%) and 80 inpatients [death (32), hospitalization >28 days (43) or ICU transfer (20)] (21.6%; 95% CI: 17.5–26.2%). Disease progression (death) for hospitalized patients was 53.1% (26.6%) and 12.8% (3.8%), respectively, for those enrolled in the ICU and general ward. In pooled analyses for both studies, predictors of disease progression were age, longer duration of symptoms at enrollment and immunosuppression. Patients hospitalized during the pandemic period had a poorer prognosis than in subsequent seasons.

Conclusions

Patients with influenza A(H1N1)pdm09, particularly when requiring hospital admission, are at high risk for disease progression, especially if they are older, immunodeficient, or admitted late in infection. These data reinforce the need for international trials of novel treatment strategies for influenza infection and serve as a reminder of the need to monitor the severity of seasonal and pandemic influenza epidemics globally.

Trial Registration

ClinicalTrials.gov Identifiers: FLU 002- {"type":"clinical-trial","attrs":{"text":"NCT01056354","term_id":"NCT01056354"}}NCT01056354, FLU 003- {"type":"clinical-trial","attrs":{"text":"NCT01056185","term_id":"NCT01056185"}}NCT01056185.     

Total immunization of children against influenza decreases morbidity in a number of diseases among elderly persons during influenza epidemic

Immunization of children aged 3-6 years in kindergartens and school children aged 7-17 years against influenza with inactivated influenza vaccine was carried out in two districts of the Moscow region. The comparison of morbidity in influenza-like diseases among the immunized children with that among nonimmunized children in control districts revealed that the effectiveness of immunization was 60.9% in kindergartens and 68.8% in schools. The analysis of morbidity in a number of diseases among 158,451 elderly persons not immunized against influenza demonstrated that, in comparison with the control districts, in those districts where mass immunization of children was carried out morbidity in influenza-like diseases among elderly persons was 3.4 times lower and, out of other 10 diseases under study, morbidity in 8 diseases was 1.5-2.6 times lower. As indicated by the data obtained in this study, total anti-influenza immunization of children in organized groups not only essentially decreased influenza morbidity among children, but also greatly decreased morbidity in influenza and a number of diseases, appearing as complications of influenza infection, among nonimmunized elderly persons during influenza epidemic.     

Effectiveness of Trivalent Inactivated Influenza Vaccine in Children Estimated by a Test-Negative Case-Control Design Study Based on Influenza Rapid Diagnostic Test Results

We assessed vaccine effectiveness (VE) against medically attended, laboratory-confirmed influenza in children 6 months to 15 years of age in 22 hospitals in Japan during the 2013–14 season. Our study was conducted according to a test-negative case-control design based on influenza rapid diagnostic test (IRDT) results. Outpatients who came to our clinics with a fever of 38°C or over and had undergone an IRDT were enrolled in this study. Patients with positive IRDT results were recorded as cases, and patients with negative results were recorded as controls. Between November 2013 and March 2014, a total of 4727 pediatric patients (6 months to 15 years of age) were enrolled: 876 were positive for influenza A, 66 for A(H1N1)pdm09 and in the other 810 the subtype was unknown; 1405 were positive for influenza B; and 2445 were negative for influenza. Overall VE was 46% (95% confidence interval [CI], 39–52). Adjusted VE against influenza A, influenza A(H1N1)pdm09, and influenza B was 63% (95% CI, 56–69), 77% (95% CI, 59–87), and 26% (95% CI, 14–36), respectively. Influenza vaccine was not effective against either influenza A or influenza B in infants 6 to 11 months of age. Two doses of influenza vaccine provided better protection against influenza A infection than a single dose did. VE against hospitalization influenza A infection was 76%. Influenza vaccine was effective against influenza A, especially against influenza A(H1N1)pdm09, but was much less effective against influenza B.     

甲型流感病毒合并肺部感染与非病毒性肺部感染的表现及治疗分析

目的:通过与非病毒性肺部感染对比,分析甲型流感病毒合并肺部感染患者的常见临床实验检查及治疗效果,为经验性治疗甲型流感病毒提供一定依据。方法:选择2017年11月至2018年4月期间在我科接受治疗的已确诊存在甲型流病毒合并肺部感染(A组)及非病毒性肺感染(B组)各25例,对于确诊的甲型流感患者给予奥司他韦抗病毒治疗一周外,两组均正常给予常规抗感染治疗,对比两组患者的炎症指标白细胞计数、中性粒细胞比例、C-反应蛋白及治疗天数、住院天数、症状消失时间、不良反应发生率。结果:两组患者的CT检查表现无统计学差异(P0.05),A组患者的白细胞计数水平明显低于B组,差异有统计学意义(P0.05),而两组患者的中性粒细胞比例及C反应蛋白水平差异无统计学意义(P0.05)。两组患者的治疗天数及住院天数差异均无统计学意义(P0.05)。两组患者在体温恢复正常时间、咳嗽消失时间、肺部湿罗音消失时间、气促消失时间等比较差异无统计学意义(P0.05)。A组不良反应发生率为16.00%(4/25),B组不良反应发生率为12.00%(3/25),组间差异无统计学意义(P0.05)。结论:甲型病毒性肺部感染常表现为血常规未见异常,常伴发不同程度炎症反应,除常规抗感染治疗外,口服抗病毒药物奥司他韦可促进疾病转归。     

Risk Factors for Death from Influenza A(H1N1)pdm09, State of S?o Paulo,Brazil, 2009

This case-control study aimed to assess the risk factors for death from influenza A(H1N1)pdm09 in patients with laboratory confirmation, who had severe acute respiratory illness-SARI and were hospitalized between June 28^th and August 29^th 2009, in the metropolitan regions of São Paulo and Campinas, Brazil. Medical charts of all the 193 patients who died (cases) and the 386 randomly selected patients who recovered (controls) were investigated in 177 hospitals. Household interviews were conducted with those who had survived and the closest relative of those who had died. 73.6% of cases and 38.1% of controls were at risk of developing influenza-related complications. The 18-to-59-year age group (OR = 2.31, 95%CI: 1.31–4.10 (reference up to 18 years of age)), presence of risk conditions for severity of influenza (OR = 1.99, 95%CI: 1.11–3.57, if one or OR = 6.05, 95%CI: 2.76–13.28, if more than one), obesity (OR = 2.73, 95%CI: 1.28–5.83), immunosuppression (OR = 3.43, 95%CI: 1.28–9.19), and search for previous care associated with the hospitalization (OR = 3.35, 95%CI: 1.75–6.40) were risk factors for death. Antiviral treatment performed within 72 hours of the onset of symptoms (OR = 0.17, 95%CI: 0.08–0.37, if within 48hours, and OR = 0.30, 95%CI: 0.11–0.81, if between 48 and 72 hours) was protective against death. The identification of high-risk patients and early treatment are important factors for reducing morbi-mortality from influenza.     

Detecting early‐warning signals of influenza outbreak based on dynamic network marker

The seasonal outbreaks of influenza infection cause globally respiratory illness, or even death in all age groups. Given early‐warning signals preceding the influenza outbreak, timely intervention such as vaccination and isolation management effectively decrease the morbidity. However, it is usually a difficult task to achieve the real‐time prediction of influenza outbreak due to its complexity intertwining both biological systems and social systems. By exploring rich dynamical and high‐dimensional information, our dynamic network marker/biomarker (DNM/DNB) method opens a new way to identify the tipping point prior to the catastrophic transition into an influenza pandemics. In order to detect the early‐warning signals before the influenza outbreak by applying DNM method, the historical information of clinic hospitalization caused by influenza infection between years 2009 and 2016 were extracted and assembled from public records of Tokyo and Hokkaido, Japan. The early‐warning signal, with an average of 4‐week window lead prior to each seasonal outbreak of influenza, was provided by DNM‐based on the hospitalization records, providing an opportunity to apply proactive strategies to prevent or delay the onset of influenza outbreak. Moreover, the study on the dynamical changes of hospitalization in local district networks unveils the influenza transmission dynamics or landscape in network level.     

Varying immunological effects in mice of intranasal infection with different strains of influenza virus

Intranasal infection of CBA/Ca mice with a sublethal dose of A/2 Japan influenza virus 305/57 decreased the blastogenic response to concanavalin A and phytohemagglutinin, and less to lipopolysaccharide andEscherichia coli bacteria. This depression of the blastogenic responses could be transferred from infected donor mice by intravenous injection of 4×10⁷ spleen cells to otherwise untreated syngenic recipient mice. Similar infections with A/Victoria 3/75 and A/Texas 1/77 influenza virus strains caused less depressing effects. Less consistent results were seen with NMRI mice. No impairment of the antibody responses to unrelated protein antigen could be noted after such intranasal influenza infection. In contrast, the IgE antibody response was particularly increased after infection with Texas virus. Some deleterious effects of Victoria and Texas virus infections on the delayed hypersensitivity response to picryl chloride were seen in CBA mice but not in NMRI mice. This immune suppression by virus infection was not reflected by the defense against intraperitoneal infection withListeria monocytogenes andE. coli. In contrast, a small increase in resistance toListeria infection was recorded. The results of this study lend little support to the hypothesis that influenza infection impairs the immunological defense against a following bacterial infection, but may result in allergy.     

Increased risk for COVID‐19 breakthrough infection in fully vaccinated patients with substance use disorders in the United States between December 2020 and August 2021

Individuals with substance use disorders (SUDs) are at increased risk for COVID‐19 infection and for adverse outcomes of the infection. Though vaccines are highly effective against COVID‐19, their effectiveness in individuals with SUDs might be curtailed by compromised immune status and a greater likelihood of exposures, added to the waning vaccine immunity and the new SARS‐CoV‐2 variants. In a population‐based cohort study, we assessed the risk, time trends, outcomes and disparities of COVID‐19 breakthrough infection in fully vaccinated SUD patients starting 14 days after completion of vaccination. The study included 579,372 individuals (30,183 with a diagnosis of SUD and 549,189 without such a diagnosis) who were fully vaccinated between December 2020 and August 2021, and had not contracted COVID‐19 infection prior to vaccination. We used the TriNetX Analytics network platform to access de‐identified electronic health records from 63 health care organizations in the US. Among SUD patients, the risk for breakthrough infection ranged from 6.8% for tobacco use disorder to 7.8% for cannabis use disorder, all significantly higher than the 3.6% in non‐SUD population (p<0.001). Breakthrough infection risk remained significantly higher after controlling for demographics (age, gender, ethnicity) and vaccine types for all SUD subtypes, except for tobacco use disorder, and was highest for cocaine and cannabis use disorders (hazard ratio, HR=2.06, 95% CI: 1.30‐3.25 for cocaine; HR=1.92, 95% CI: 1.39‐2.66 for cannabis). When we matched SUD and non‐SUD individuals for lifetime comorbidities and adverse socioeconomic determinants of health, the risk for breakthrough infection no longer differed between these populations, except for patients with cannabis use disorder, who remained at increased risk (HR=1.55, 95% CI: 1.22‐1.99). The risk for breakthrough infection was higher in SUD patients who received the Pfizer than the Moderna vaccine (HR=1.49, 95% CI: 1.31‐1.69). In the vaccinated SUD population, the risk for hospitalization was 22.5% for the breakthrough cohort and 1.6% for the non‐breakthrough cohort (risk ratio, RR=14.4, 95% CI: 10.19‐20.42), while the risk for death was 1.7% and 0.5% respectively (RR=3.5, 95% CI: 1.74‐7.05). No significant age, gender and ethnic disparities for breakthrough infection were observed in vaccinated SUD patients. These data suggest that fully vaccinated SUD individuals are at higher risk for breakthrough COVID‐19 infection, and this is largely due to their higher prevalence of comorbidities and adverse socioeconomic determinants of health compared with non‐SUD individuals. The high frequency of comorbidities in SUD patients is also likely to contribute to their high rates of hospitalization and death following breakthrough infection.     

The Temporal Trend of Influenza-Associated Morbidity and the Impact of Early Appearance of Antigenic Drifted Strains in a Southeast Asian Country

Globally, influenza infection is a major cause of morbidity and mortality in the elderly, who are suggested to be the major target group for trivalent influenza vaccine (TIV) vaccination by World Health Organization. In spite of an increasing trend in vaccine coverage rates in many countries, the effect of vaccination among the elderly in reducing hospitalization and mortality remains controversial. In this study, we conducted a historical cohort study to evaluate the temporal pattern of influenza-associated morbidity among persons older than 64 years over a decade. The temporal patterns of influenza-associated morbidity rates among the elderly older than 64 years indicated that Taiwan''s elderly P&I outpatient visits have been decreasing since the beginning of the 1999–2000 influenza season; however, hospitalization has been increasing despite significant increases in vaccine coverage. The propensity score logistic regression model was implemented to evaluate the source of bias and it was found that the TIV-receiving group had a higher propensity score than the non-receiving group (P<0.0001). In order to investigate the major factors affecting the temporal pattern of influenza-associated morbidity, we then used the propensity score as a summary confounder in a multivariate Poisson regression model based on the trimmed data. Our final models suggested that the factors affected the temporal pattern of morbidity differently. The variables including co-morbidity, vaccination rate, influenza virus type A and B isolation rate were associated with increased outpatient visits and hospitalization (p<0.05). In contrast, variables including high propensity score, increased 1°C in temperature, matching vaccine strains of type A/H1N1 and type B were associated with decreased outpatient visits and hospitalization (p<0.05). Finally, we assessed the impact of early appearance of antigenic-drifted strains and concluded that an excess influenza-associated morbidity substantial trends toward higher P&I hospitalization, but not outpatient visits, during the influenza season with early appearance of antigenic-drifted strains.     

Prophylactic and therapeutic efficacies of Ingavirin, a novel Russian chemotherapeutic, with respect to influenza pathogen A (H5N1)

The experimental study of the Ingavirin efficacy against the influenza virus A (H5N1) on intranasally-infected albino mice vs. Tamiflue and Arbidol showed that when used for the prophylaxis, urgent prophylaxis and therapy it was effective in the protectiom of the animals from death. The efficient dose for the prophylaxis of the influenza infection was 5 mg/kg (protective efficacy of 46.7%) and for the urgent prophylaxis and therapy it was 15 mg/kg (protective efficacy of 40.0 and 35.0% respectively).     

Influence of multiplicity of immunizations of children with inactivated influenza vaccine on immune response and the effectiveness of protection

The formation of immunity and epidemiological effectiveness of inactivated influenza vaccines in children, regularly immunized against influenza for three years, were evaluated. The study revealed that a year after each immunization the number of children having antibodies in liters regarded as protective decreased 2-2.5 times. At the periods of epidemics morbidity rate among the vaccines dynamically decreased in these years 1.3, 2.0 and 2.8 times. Considering that a year after the second immunization a high immune stratum (60-78%) was retained in the group under study, we propose that annual immunization of the same children be limited by a period of three years, followed by an interval of one year.     

Effects of heat-killed <Emphasis Type="Italic">Lactobacillus plantarum</Emphasis> against influenza viruses in mice

The potential use of dietary measures to treat influenza can be an important alternative for those who lack access to influenza vaccines or antiviral drugs. Lactobacillus plantarum (Lp) is one of many lactic acid bacteria that grow in ‘kimchi’, an essential part of Korean meal, and several strains of Lp reportedly show protective effects against influenza. Using heat-killed Lp (nF1) isolated from kimchi, which is known for its immunomodulatory effects, we investigated whether regular oral intake of nF1 could influence the outcome of influenza virus infection in a mouse model. In a lethal challenge with influenza A (H1N1 and H3N2 subtypes) and influenza B (Yamagata lineage) viruses, daily oral administration of nF1 delayed the mean number of days to death of the infected mice and resulted in increased survival rates compared with those of the non-treated mice. Consistent with these observations, nF1 treatment also significantly reduced viral replication in the lungs of the infected mice. Taken together, our results might suggest the remedial potential of heatkilled Lactobacillus probiotics against influenza.     

Galectin-1 binds to influenza virus and ameliorates influenza virus pathogenesis

Innate immune response is important for viral clearance during influenza virus infection. Galectin-1, which belongs to S-type lectins, contains a conserved carbohydrate recognition domain that recognizes galactose-containing oligosaccharides. Since the envelope proteins of influenza virus are highly glycosylated, we studied the role of galectin-1 in influenza virus infection in vitro and in mice. We found that galectin-1 was upregulated in the lungs of mice during influenza virus infection. There was a positive correlation between galectin-1 levels and viral loads during the acute phase of viral infection. Cells treated with recombinant human galectin-1 generated lower viral yields after influenza virus infection. Galectin-1 could directly bind to the envelope glycoproteins of influenza A/WSN/33 virus and inhibit its hemagglutination activity and infectivity. It also bound to different subtypes of influenza A virus with micromolar dissociation constant (K(d)) values and protected cells against influenza virus-induced cell death. We used nanoparticle, surface plasmon resonance analysis and transmission electron microscopy to further demonstrate the direct binding of galectin-1 to influenza virus. More importantly, we show for the first time that intranasal treatment of galectin-1 could enhance survival of mice against lethal challenge with influenza virus by reducing viral load, inflammation, and apoptosis in the lung. Furthermore, galectin-1 knockout mice were more susceptible to influenza virus infection than wild-type mice. Collectively, our results indicate that galectin-1 has anti-influenza virus activity by binding to viral surface and inhibiting its infectivity. Thus, galectin-1 may be further explored as a novel therapeutic agent for influenza.