Influenza and dengue virus co‐infection impairs monocyte recruitment to the lung,increases dengue virus titers,and exacerbates pneumonia

Co‐infections of influenza virus and bacteria are known to cause severe disease, but little information exists on co‐infections with other acute viruses. Seasonal influenza and dengue viruses (DENV) regularly co‐circulate in tropical regions. The pandemic spread of influenza virus H1N1 (hereafter H1N1) in 2009 led to additional severe disease cases that were co‐infected with DENV. Here, we investigated the impact of co‐infection on immune responses and pathogenesis in a new mouse model. Co‐infection of otherwise sublethal doses of a Nicaraguan clinical H1N1 isolate and two days later with a virulent DENV2 strain increased systemic DENV titers and caused 90% lethality. Lungs of co‐infected mice carried both viruses, developed severe pneumonia, and expressed a unique pattern of host mRNAs, resembling only partial responses against infection with either virus alone. A large number of monocytes were recruited to DENV‐infected but not to co‐infected lungs, and depletion and adoptive transfer experiments revealed a beneficial role of monocytes. Our study shows that co‐infection with influenza and DENV impairs host responses, which fail to control DENV titers and instead, induce severe lung damage. Further, our findings identify key inflammatory pathways and monocyte function as targets for future therapies that may limit immunopathology in co‐infected patients.     

An early ‘classical’ swine H1N1 influenza virus shows similar pathogenicity to the 1918 pandemic virus in ferrets and mice

The 1918 pandemic influenza virus has demonstrated significant pathogenicity in animal models and is the progenitor of ‘classical’ swine and modern seasonal human H1N1 lineages. Here we characterize the pathogenicity of an early ‘classical’ swine H1N1 influenza A virus isolated in 1931 compared to the pathogenicity of the 1918 pandemic virus and a seasonal H1N1 virus in mice and ferrets. A/Swine/Iowa/31 (Sw31) and the 1918 influenza viruses were uniformly lethal in mice at low doses and produced severe lung pathology. In ferrets, Sw31 and 1918 influenza viruses caused severe clinical disease and lung pathology with necrotizing bronchiolitis and alveolitis. The modern H1N1 virus caused little disease in either animal model. These findings revealed that in these models the virulence factors of the 1918 influenza virus are likely preserved in the Sw31 virus and suggest that early swine viruses may be a good surrogate model to study 1918 virulence and pathogenesis.     

Pulmonary cell susceptibility in mice and rats to influenza virus when infected in vivo and in vitro

The purpose of the case study was to evaluate comparatively the relative contribution of cell susceptibility and the inhibiting effect of factors of pulmonary epithelial lining in mice and rats to influenza virus A/Aichi/2/68 (H3N2) adapted to mice as related with the development of infection process in the lungs of experimental animals when infected in vivo and in vitro. Mice and rats were infected aerogenically with different doses of influenza virus. The primary cell-culture suspensions sampled from the lungs of mice and rats were used to study the adsorption and dynamics of influenza virus production in infection by different dose of influenza virus in vitro. The cell suspensions were shown to be able to produce the influenza virus for as long as 48 hours after infection. It was for the first time that the results denoted the identical susceptibility of primary pulmonary cells in mice and rats to influenza virus. A lower pulmonary susceptibility to influenza virus in rats versus mice could be indicative of that the surface factors of epithelial lining contribute essentially to shaping the pulmonary susceptibility to influenza virus since there is no difference of the susceptibility of pulmonary cells to influenza virus between the two above animals' species.     

NK cells exacerbate the pathology of influenza virus infection in mice

NK cells offer a first line of defense against viruses and are considered beneficial to the host during infection. Nevertheless, little is understood regarding the phenotype and function of NK cells in the lung during influenza virus infection. We found that the frequency of NK cells in mouse lung increased during influenza infection, with the majority of a mature phenotype. Cell surface CD107a and intracellular IFN‐γ were detected in cells expressing multiple NK‐cell receptors in infected lung, suggesting that NK cells were activated during infection. The activating receptor NKp46 was predominantly negative on such cells, possibly as a result of encountering influenza HA. Depletion of NK cells in vivo with anti‐asialo GM1 or anti‐NK1.1 reduced mortality from influenza infection and surviving mice recovered their body weight. Pathology induced by NK cells was only observed with high, not medium or low‐dose influenza infection, indicating that the severity of infection influences NK‐cell‐mediated pathology. Furthermore, adoptive transfer of NK cells from influenza‐infected lung, but not uninfected lung, resulted in more rapid weight loss and increased mortality of influenza‐infected mice. Our results indicate that during severe influenza infection of the lung, NK cells have a deleterious impact on the host, promoting mortality.     

Critical role of CXCL4 in the lung pathogenesis of influenza (H1N1) respiratory infection

Annual epidemics and unexpected pandemics of influenza are threats to human health. Lung immune and inflammatory responses, such as those induced by respiratory infection influenza virus, determine the outcome of pulmonary pathogenesis. Platelet-derived chemokine (C-X-C motif) ligand 4 (CXCL4) has an immunoregulatory role in inflammatory diseases. Here we show that CXCL4 is associated with pulmonary influenza infection and has a critical role in protecting mice from fatal H1N1 virus respiratory infection. CXCL4 knockout resulted in diminished viral clearance from the lung and decreased lung inflammation during early infection but more severe lung pathology relative to wild-type mice during late infection. Additionally, CXCL4 deficiency decreased leukocyte accumulation in the infected lung with markedly decreased neutrophil infiltration into the lung during early infection and extensive leukocyte, especially lymphocyte accumulation at the late infection stage. Loss of CXCL4 did not affect the activation of adaptive immune T and B lymphocytes during the late stage of lung infection. Further study revealed that CXCL4 deficiency inhibited neutrophil recruitment to the infected mouse lung. Thus the above results identify CXCL4 as a vital immunoregulatory chemokine essential for protecting mice against influenza A virus infection, especially as it affects the development of lung injury and neutrophil mobilization to the inflamed lung.     

Pathological post‐mortem findings in lungs infected with SARS‐CoV‐2

Italy was the first European nation to be massively infected by SARS‐CoV‐2. Up to the end of May 2020, more than 33,000 deaths had been recorded in Italy, with a large prevalence among males, those over 75 years of age, and in association with co‐morbidities. We describe the lung pathological and immunohistochemical post‐mortem findings at the autopsy of nine patients who died of SARS‐CoV‐2‐associated disease. We found in the lung tissues of all patients histological changes consistent with diffuse alveolar damage in various evolution phases ranging from acute exudative to acute proliferative to fibrotic phase. Alveolar damage was associated with prominent involvement of the vascular component in both the interstitial capillaries and the mid‐size vessels, with capillary fibrin micro‐thrombi, as well as organized thrombi even in medium‐sized arteries, in most cases not related to sources of embolism. Eosinophilic infiltrate was also seen, probably reactive to pharmacological treatment. Viral RNA of SARS‐CoV‐2 was detected from the lung tissues of all the nine patients. Immunohistochemistry for the receptor of the SARS‐CoV‐2, ACE2, and its priming activator TMPRSS2 revealed that both proteins co‐localize in airway cells. In particular, the ACE2 protein was expressed in both endothelial cells and alveolar type I and II pneumocytes in the areas of histological diffuse alveolar damage (DAD). Pneumocytes, but not endothelial cells, also expressed TMPRSS2. There are no distinctive histological features of SARS‐CoV‐2 infection with respect to SARS‐CoV‐1 and other DAD with different aetiology. The identification of the cause of death in the course of SARS‐CoV‐2 infection is more likely multi‐factorial. © 2020 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Histopathological Evaluation of the Diversity of Cells Susceptible to H5N1 Virulent Avian Influenza Virus

Patients infected with highly pathogenic avian influenza A H5N1 viruses (H5N1 HPAIV) show diffuse alveolar damage. However, the temporal progression of tissue damage and repair after viral infection remains poorly defined. Therefore, we assessed the sequential histopathological characteristics of mouse lung after intranasal infection with H5N1 HPAIV or H1N1 2009 pandemic influenza virus (H1N1 pdm). We determined the amount and localization of virus in the lung through IHC staining and in situ hybridization. IHC used antibodies raised against the virus protein and antibodies specific for macrophages, type II pneumocytes, or proliferating cell nuclear antigen. In situ hybridization used RNA probes against both viral RNA and mRNA encoding the nucleoprotein and the hemagglutinin protein. H5N1 HPAIV infection and replication were observed in multiple lung cell types and might result in rapid progression of lung injury. Both type II pneumocytes and macrophages proliferated after H5N1 HPAIV infection. However, the abundant macrophages failed to block the viral attack, and proliferation of type II pneumocytes failed to restore the damaged alveoli. In contrast, mice infected with H1N1 pdm exhibited modest proliferation of type II pneumocytes and macrophages and slight alveolar damage. These results suggest that the virulence of H5N1 HPAIV results from the wide range of cell tropism of the virus, excessive virus replication, and rapid development of diffuse alveolar damage.Seasonal, pandemic, and zoonotic influenza A virus infections show substantial morbidity and mortality in humans. Seasonal influenza A virus infections in humans are usually mild and cause pneumonia only in a few infected individuals. Pandemic influenza virus infections vary in their disease outcome. Zoonotic influenza virus infections in humans vary from self-limiting conjunctivitis to severe, often fatal, pneumonia. Highly pathogenic avian influenza H5N1 virus (H5N1 HPAIV), implicated in poultry outbreaks,^1,2 can be transmitted zoonotically to humans, as has been observed in areas of Asia and Africa.^3–5 Fatal outcomes have been reported at approximately 60% in the sporadic transmission of this avian influenza H5N1 virus to humans.^5–7 There is no evidence that the avian influenza virus has become efficiently transmissible among humans, a change that could result in a new pandemic.⁸The outcome after infection with influenza virus can range from slight to severe illness, depending on the kinds of cells that are affected during lung tissue infection.^9–11 Events occurring early in infection determine the extent of damage, which can range from bronchitis to pneumonia. In the most severe cases, diffuse alveolar damage (DAD) may be induced during the early stages, and healing and/or scarring may ensue, depending on the persistence of disease. Occasionally, bacterial infection also may occur, with associated effects expressed mainly in the later stages of the disease. Pathological damage caused by influenza viruses in humans and in animal models depends on the virulence of the infective agent and on the host response. All influenza viruses infect the respiratory tract epithelium from the nasal passages to the bronchioles; however, highly virulent viruses (eg, H1N1 1918 and H5N1 HPAIV) tend to infect pneumocytes and resident macrophages in the alveoli. In susceptible individuals, inflammation of the alveolar walls results in DAD. In contrast, low-virulence viruses (seasonal H1N1) primarily cause inflammation, congestion, and epithelial necrosis of the trachea, bronchi, and bronchioles. Tissue tropism is an important factor, and depends largely on the ability of the virus to attach to the host cell.^12–14 We investigated virus replication and histopathological progression of lung tissue in mice infected with H5N1 HPAIV, particularly focusing on the lower respiratory tract and alveoli, with direct comparison to the histopathological characteristics of mice infected with H1N1 pandemic (pdm) influenza virus 2009 virus.     

Humoral immune responses during asthma and influenza co-morbidity in mice

Humoral immunity serve dual functions of direct pathogen neutralization and enhancement of leukocyte function. Antibody classes are determined by antigen triggers, and the resulting antibodies can contribute to disease pathogenesis and host defense. Although asthma and influenza are immunologically distinct diseases, since we have found that allergic asthma exacerbation promotes antiviral host responses to influenza A virus, we hypothesized that humoral immunity may contribute to allergic host protection during influenza. C57BL/6J mice sensitized and challenged with Aspergillus fumigatus (or not) were infected with pandemic influenza A/CA/04/2009 virus. Negative control groups included naïve mice, and mice with only ‘asthma’ or influenza. Concentrations of antibodies were quantified by ELISA, and in situ localization of IgA- and IgE-positive cells in the lungs was determined by immunohistochemistry. The number and phenotype of B cells in spleens and mediastinal lymph nodes were determined by flow cytometry at predetermined timepoints after virus infection until viral clearance. Mucosal and systemic antibodies remained elevated in mice with asthma and influenza with prominent production of IgE and IgA compared to influenza-only controls. B cell expansion was prominent in the mediastinal lymph nodes of allergic mice during influenza where most cells produced IgG₁ and IgA. Although allergy-skewed B cell responses dominated in mice with allergic airways inflammation during influenza virus infection, virus-specific antibodies were also induced. Future studies are required to identify the mechanisms involved with B cell activation and function in allergic hosts facing respiratory viral infections.     

Acute murine H5N1 influenza A encephalitis

Avian influenza A virus H5N1 has the proven capacity to infect humans through cross‐species transmission, but to date, efficient human‐to‐human transmission is limited. In natural avian hosts, animal models and sporadic human outbreaks, H5N1 infection has been associated with neurological disease. We infected BALB/c mice intranasally with H5N1 influenza A/Viet Nam/1203/2004 to study the immune response during acute encephalitis. Using immunohistochemistry and in situ hybridization, we compared the time course of viral infection with activation of immunity. By 5 days postinfection (DPI), mice had lost substantial body weight and required sacrifice by 7 DPI. H5N1 influenza was detected in the lung as early as 1 DPI, whereas infected neurons were not observed until 4 DPI. H5N1 infection of BALB/c mice developed into severe acute panencephalitis. Infected neurons lacked evidence of a perineuronal net and exhibited signs of apoptosis. Whereas lung influenza infection was associated with an early type I interferon (IFN) response followed by a reduction in viral burden concordant with appearance of IFN‐γ, the central nervous system environment exhibited a blunted type I IFN response.     

The ability of pandemic influenza virus hemagglutinins to induce lower respiratory pathology is associated with decreased surfactant protein D binding

Pandemic influenza viral infections have been associated with viral pneumonia. Chimeric influenza viruses with the hemagglutinin segment of the 1918, 1957, 1968, or 2009 pandemic influenza viruses in the context of a seasonal H1N1 influenza genome were constructed to analyze the role of hemagglutinin (HA) in pathogenesis and cell tropism in a mouse model. We also explored whether there was an association between the ability of lung surfactant protein D (SP-D) to bind to the HA and the ability of the corresponding chimeric virus to infect bronchiolar and alveolar epithelial cells of the lower respiratory tract. Viruses expressing the hemagglutinin of pandemic viruses were associated with significant pathology in the lower respiratory tract, including acute inflammation, and showed low binding activity for SP-D. In contrast, the virus expressing the HA of a seasonal influenza strain induced only mild disease with little lung pathology in infected mice and exhibited strong in vitro binding to SP-D.     

T cells and ILC2s are major effector cells in influenza‐induced exacerbation of allergic airway inflammation in mice

Influenza virus infection is an important cause of severe asthma exacerbations, but it remains unclear how a Th1‐mediated antiviral response triggers a prototypical Th2 disease. We investigated CD4⁺ T cells and group 2 innate lymphoid cells (ILC2s) in influenza virus‐infected mice. We found that ILC2s accumulated in the lung rapidly after influenza virus infection, but the induction of IL‐5 and IL‐13 secretion was delayed and concomitant with T cell activation. In an influenza‐induced exacerbation of allergic airway inflammation model we noticed an initial reduction of ILC2 numbers and cytokine production in broncho‐alveolar lavage compared to chronic house dust mite (HDM)‐mediated airway inflammation alone. ILC2s phenotype was characterized by low T1/ST2, ICOS, KLRG1, and CD25 expression, resembling naïve ILC2s. The contribution of ILC2s to type 2 cytokine production in the early stage of the influenza‐induced exacerbation was limited. In contrast, T cells showed increased IL‐4 and IL‐5 production when exposed to both HDM and influenza virus. Upon virus clearance, ILC2s regained an activated T1/ST2^highICOS^highKLRG1^highCD25^high phenotype paired with cytokine production and were major contributors to the type 2 cytokine milieu. Collectively, our data indicate that both T cells and ILC2s contribute to influenza‐induced exacerbation of allergic airway inflammation, but with different kinetics.     

Mechanistic perspective of the oxido‐immunopathologic resolution property of kolaviron in mice influenza pneumonitis

Implicated in influenza‐associated pathology are innate defence overzealousness and unabated secretion of oxidative tissue‐sensitive antimicrobial agents. At different time points, mice were pre‐treated with kolaviron (400 mg/kg), a natural antioxidant and anti‐inflammatory agent, and subsequently challenged with 2 LD₅₀ influenza A/H3N2/Perth/16/09 virus. After euthanasia at day 6, blood, lungs, liver and spleen were collected and processed for biochemical, immunohistochemical and flow cytometric assessment of redo‐inflammatory imbalance, cytokine storm indices and T helper 1 host response. Previously kolaviron was reported to delay mortality onset, improve morbidity and attenuate myeloperoxidase activity and nitric oxide production with minimal impact on viral clearance. This study additionally confirmed nitric oxide, but not hydrogen peroxide, as the major culprit implicated in influenza virus‐induced oxido‐pathology. Systemic effect of the sustained inflammation and nitrosative stress was more prominent in the spleen and lung than in the liver of mice infected with A/H3N2/Perth/16/09. Influential to immunopathology was heightened pulmonary expression of IL‐1β, RANTES, IL‐10, MCP‐1, NF‐κB, iNOS and COX‐2. However, kolaviron combated the influenza‐established nitrative stress, reversed the elicited cytokine storm and restored the oxidized environment to a reductive milieu. Our data also suggest that kolaviron administration early in infection may foster CD4⁺ response. These data indicate that kolaviron may confer disease‐dwindling properties during acute influenza infection via a system‐wide protective approach involving multiple targets especially at the early stage of the infection.     

Differential microRNA expression and virulence of avian, 1918 reassortant, and reconstructed 1918 influenza A viruses

Infections with highly pathogenic H5N1 avian (HPAI) and 1918 pandemic H1N1 influenza viruses cause uncontrolled local and systemic inflammation. The mechanism for this response is poorly understood, despite its importance as a determinant of virulence. Therefore we profiled cellular microRNAs of lung tissue from cynomolgus macaques (Macaca fascicularis) infected with a HPAI and a less pathogenic 1918 H1N1 reassortant virus to understand microRNA contribution to host response. We identified 23 microRNAs associated with the extreme virulence of HPAI, with expression patterns inversely correlated with that of predicted gene targets. Pathway analyses confirmed that these targets were associated with aberrant and uncontrolled inflammatory responses and increased cell death. Importantly, similar microRNAs were associated with lethal 1918 pandemic virus infections in mice. This study suggests that virulence of highly pathogenic influenza viruses may be mediated in part by cellular microRNA through dysregulation of genes critical to the inflammatory process.     

A single point mutation (Y89F) within the non-structural protein 1 of influenza A viruses limits epithelial cell tropism and virulence in mice

The nonstructural protein 1 (A/NS1) of influenza A viruses (IAV) harbors several src homology (SH)-binding motifs (bm) that mediate interactions with cellular proteins. In contrast to the sequence variability of the second SH3bm, tyrosine 89, within the SH2bm is a highly conserved residue among IAV strains. This prompted us to evaluate the necessity of this SH2bm for IAV virulence. In an in vivo mouse model, we observed drastic reductions in weight loss, mortality, and virus titers in lung and bronchoalveolar lavage fluid after infection with the mutant virus PR8 A/NS1-Y89F (PR8 Y89F) when compared with wild-type virus (PR8 wt). Concomitantly, we observed decreased inflammation and less severe pathologic changes, reflecting reduced levels of virus titers. At histologic analysis, lungs infected with PR8 wt virus showed widespread destruction of the bronchiolar epithelium, with extensive distribution of virus antigen within tracheal, bronchial, bronchiolar, and alveolar epithelium. In marked contrast, the bronchiolar epithelium after infection with the mutant PR8 Y89F virus was entirely intact, and the severity and extent of viral infection was reduced and strongly restricted to alveoli. These findings demonstrate that change of a single residue of the highly conserved SH2bm within the A/NS1 results in restricted virus spread in mouse lung and strongly reduced virulence, which illustrates the necessity of the SH2bm for IAV-induced pathogenicity.     

In Vivo Anti-Influenza Virus Activity of Kampo (Japanese Herbal) Medicine “Sho-Seiryu-To”—Effects on Aged Mice, Against Subtypes of a Viruses and B Virus, and Therapeutic Effect

When aged BALB/c mice (∼6 months old) were treated with a Kampo (Japanese herbal) medicine “Sho-seiryu-to (SST)” (1 g/kg, 10 times) orally from 7 days before to 4 days after the infection and infected with mouse-adapted influenza virus A/PR/8/34 (H1N1 subtype) by nasal site-restricted infection, replication of the virus in the broncho-alveolar cavity was efficiently inhibited at 5 days after infection in comparison with water-treated mice. The antiviral IgA antibody in the broncho-alveolar wash of the SST treated aged mice increased significantly. When mice (7 weeks old) were administered orally with SST (1 and 2 g/kg, 7 times) from 4 days before to 3 days after the infection and infected with mouse-adapted influenza virus A/Guizhou/54/89 (H3N2 subtype) or B/Ibaraki/2/85, replication of the viruses in the nasal cavity and lung were significantly inhibited at 4 days after infection in comparison with control mice. When mice infected with influenza virus A/Fukuoka/C29/85 (H3N2) before 14 days were secondary infected with A/PR/8 virus and administered orally with SST (1 g/kg, 5 times) from 2 h to 5 days after the secondary infection, replication of the virus in both nasal and broncho-alveolar cavities were significantly inhibited at 5 days after the secondary infection in comparison with water-treated control. Oral administration of SST (1 g/kg, 18 times) from 7 days before to 14 days after vaccination followed by secondary nasal inoculation of influenza HA vaccine (5 µglmouse) at 14 days after the first vaccination significantly augmented nasal antiviral IgA antibody and broncho-alveolar and serum antiviral IgG antibodies. These results suggest that SST is useful for influenza virus infection on aged persons and for cross-protection of subtypes of influenza A viruses and influenza B virus. SST is also useful for the treatment of influenza virus infection on human which has a history of influenza virus infection and/or influenza vaccination.     

Functional and antigenic analyses of the 1918 influenza virus haemagglutinin using a recombinant vaccinia virus expression system

The influenza pandemic of 1918 caused unprecedented levels of morbidity and mortality in its 12-month period of circulation around the globe. The haemagglutinin molecule has been shown to affect the pathogenicity of some subtypes of influenza A viruses. Using a recombinant vaccinia system that allowed expression of the 1918 influenza haemagglutinin, we performed functional assays to assess the glycoprotein's involvement in determining the high pathogenicity of the 1918 virus. We show that in respect of expression levels, proteolytic processing, receptor-binding, membrane fusion and antigenic properties, the haemagglutinin of the 1918 virus is unremarkable when compared with the haemagglutinins of other 'early' H1 influenza viruses. This suggests that whilst the 1918 haemagglutinin, as a new/novel antigen in the human population, was responsible for the influenza pandemic its functions per se were not responsible for the high mortality and acute symptoms experienced by patients infected with the 1918 influenza virus.     

The threat and prospects for control of an influenza pandemic

Influenza constitutes the most widespread and significant respiratory infectious disease in the world, resulting in increased morbidity, mortality and economic loss each epidemic year. Pandemic influenza is a worldwide epidemic usually caused by a new virus variant to which the majority of the population has no immunity. As demonstrated in the devastating pandemic of 1918 to 1919, a pandemic virus may infect 30 to 50% of the worlds population and kill 1 to 2% of those infected. Pandemic control must be a concerted and co-ordinated world strategy and under the auspices of the World Health Organization, pandemic preparedness plans have been formulated, including: intensified surveillance for more rapid identification of new reassortant viruses with potential human virulence and infectivity, laboratory characterization of the new viruses so that vaccine may be prepared, development of techniques for more rapid vaccine production and the manufacture and stock piling of antiviral drugs. The H5N1 outbreak of virulent chicken influenza in 1997 in Hong Kong which resulted in the deaths of six of 18 infected persons serves as a wake-up call. Should such a virus attain high transmissibility in humans, a pandemic of tragic proportions might ensue. Even though the timing of onset of the next pandemic cannot be precisely predicted, world governments must understand the urgency of the problem and increase funding for influenza pandemic control.     

抗三价流感病毒亚单位疫苗IgY防治小鼠流感病毒感染的实验研究

目的:探讨抗三价流感病毒亚单位疫苗IgY(Immunoglobulin Yolk)预防及治疗流感病毒感染小鼠的作用。方法:建立A/fm/1/47(H1N1)流感小鼠模型;分5组,观察各组小鼠死亡率,脾、肺指数及肺指数抑制率。结果:0.2%抗三价流感病毒亚单位疫苗IgY于攻毒前24、6、1小时滴鼻3次显著地预防流感病毒致死率(30.0%),而攻毒后1、6、24小时分别滴鼻3次,此后每天滴鼻1次,持续5天,致死率为20.0%,两组与阳性对照组(致死率90.0%)、非特异性IgY预防和治疗组(致死率80.0%,70.0%)比较差异显著(P<0.01)。0.2%抗三价流感病毒亚单位疫苗IgY预防组和治疗组肺指数显著低于阳性对照组(P<0.05~0.01),其治疗组也低于非特异性IgY预防和治疗组(P<0.05)。结论:抗三价流感病毒亚单位疫苗IgY感染前后24小时内多次滴鼻能有效地预防和治疗流感病毒感染。     

Insights on influenza pathogenesis from the grave

The 1918-1919 'Spanish' influenza virus caused the worst pandemic in recorded history and resulted in approximately 50 million deaths worldwide. Efforts to understand what happened and to use these insights to prevent a future similar pandemic have been ongoing since 1918. In 2005 the genome of the 1918 influenza virus was completely determined by sequencing fragments of viral RNA preserved in autopsy tissues of 1918 victims, and using reverse genetics, infectious viruses bearing some or all the 1918 virus gene segments were reconstructed. These studies have yielded much information about the origin and pathogenicity of the 1918 virus, but many questions still remain.