Seroprevalence of seasonal and pandemic influenza A viruses in domestic cats

Infection of domestic cats with pandemic H1N1 influenza virus has recently been documented. We conducted a seroprevalence survey and found that 17 of 78 (21.8%) cats sampled during the 2009–2010 influenza season had antibody titers ≥40 against the novel H1N1 strain by hemagglutinin-inhibition assay, compared to only 1 of 39 (2.6%) sampled in 2008 prior to emergence of the pandemic (p = 0.006). Seroprevalance of seasonal H1N1 (41.9%) and H3N2 (25.6%) viruses was similarly high. These data reflecting past infection of household cats raise the possibility that they may act as a vector of influenza transmission within households.     

Serologic Evidence of Pandemic Influenza Virus H1N1 2009 Infection in Cats in China

Infection of domestic cats with (H1N1) pandemic 2009 (pdm09) influenza A virus has recently been documented. In this paper, we report for the first time the sporadically current seroprevalence of (H1N1) pdm09 influenza A virus infection in cats in China. Thirteen of 1,080 sera were found positive by nucleoprotein (NP)-specific enzyme-linked immunosorbent assays (ELISAs) in different cat populations in southern China. It is very important to stress further surveillance of pandemic (H1N1) 2009 influenza A virus in cats in southern China.     

Influenza A virus (H5N1) infection in cats causes systemic disease with potential novel routes of virus spread within and between hosts

The ongoing outbreak of avian influenza A virus (subtype H5N1) infection in Asia is of great concern because of the high human case fatality rate and the threat of a new influenza pandemic. Case reports in humans and felids suggest that this virus may have a different tissue tropism from other influenza viruses, which are normally restricted to the respiratory tract in mammals. To study its pathogenesis in a mammalian host, domestic cats were inoculated with H5N1 virus intratracheally (n = 3), by feeding on virus-infected chicks (n = 3), or by horizontal transmission (n = 2) and examined by virological and pathological assays. In all cats, virus replicated not only in the respiratory tract but also in multiple extra-respiratory tissues. Virus antigen expression in these tissues was associated with severe necrosis and inflammation 7 days after inoculation. In cats fed on virus-infected chicks only, virus-associated ganglioneuritis also occurred in the submucosal and myenteric plexi of the small intestine, suggesting direct infection from the intestinal lumen. All cats excreted virus not only via the respiratory tract but also via the digestive tract. This study in cats demonstrates that H5N1 virus infection causes systemic disease and spreads by potentially novel routes within and between mammalian hosts.     

Human and avian influenza viruses target different cells in the lower respiratory tract of humans and other mammals

Viral attachment to the host cell is critical for tissue and species specificity of virus infections. Recently, pattern of viral attachment (PVA) in human respiratory tract was determined for highly pathogenic avian influenza virus of subtype H5N1. However, PVA of human influenza viruses and other avian influenza viruses in either humans or experimental animals is unknown. Therefore, we compared PVA of two human influenza viruses (H1N1 and H3N2) and two low pathogenic avian influenza viruses (H5N9 and H6N1) with that of H5N1 virus in respiratory tract tissues of humans, mice, ferrets, cynomolgus macaques, cats, and pigs by virus histochemistry. We found that human influenza viruses attached more strongly to human trachea and bronchi than H5N1 virus and attached to different cell types than H5N1 virus. These differences correspond to primary diagnoses of tracheobronchitis for human influenza viruses and diffuse alveolar damage for H5N1 virus. The PVA of low pathogenic avian influenza viruses in human respiratory tract resembled that of H5N1 virus, demonstrating that other properties determine its pathogenicity for humans. The PVA in human respiratory tract most closely mirrored that in ferrets and pigs for human influenza viruses and that in ferrets, pigs, and cats for avian influenza viruses.     

Influenza infection in humans and pigs in southeastern China

Summary The three last pandemic strains of influenza A virus-Asian/57, Hong Kong/68 and Russian/77 — are believed to have originated in China. The strains responsible for the 1957 and 1968 human pandemics were reassortants incorporating both human and avian influenza viruses, which may have arisen in pigs. We therefore undertook a population-based study in the Nanchang region of Central China to establish the prevalence, types and seasonal pattern of human influenza infection and to screen serum samples from animals and humans for evidence of interspecies transmission of influenza viruses.Two definite influenza seasons were demonstrated, one extending from November to March and the other July to September. The profile of antibodies to commonly circulating human influenza viruses was no different in Nanchang and neighboring rural communities than in Memphis, Tennessee, USA. In particular, Chinese women who raised pigs in their homes were no more likely to have been exposed to influenza virus than were subjects who seldom or never had contact with pigs. However, we did obtain evidence using isolated H7 protein in an enzyme-linked immunoabsorbent assay for infection of pig farmers by an avian H7 influenza virus suggesting that influenza A viruses may have been transmitted directly from ducks to humans. The results of the serological survey also indicated that pigs in or near Nanchang were infected by human H1N1 and H3N2 influenza viruses, but not with typical swine viruses. We found no serological evidence for H2 influenza viruses in humans after 1968.     

The pathogenesis of influenza virus infections: the contributions of virus and host factors

Influenza viruses cause acute respiratory inflammation in humans and symptoms such as high fever, body aches, and fatigue. Usually these symptoms improve after several days; however, the 2009 pandemic H1N1 influenza virus [influenza A(H1N1) 2009] is more pathogenic than seasonal influenza viruses and the pathogenicity of highly pathogenic H5N1 viruses is still higher. The 1918 influenza pandemic virus caused severe pneumonia, resulting in an estimated 50 million deaths worldwide. Several virulence factors have been identified in these virus strains, but host factors are also responsible for the pathogenesis of infections caused by virulent viruses. Here, we review the contributions of both virus and host factors to the pathogenesis of these viral infections.     

2009甲型H1N1流感大流行期间北京儿童的流感监测

目的 了解2009年甲型H1N1流感大流行期间北京地区儿童中流感流行的情况.方法 采用WHO推荐的实时荧光定量RT-PCR和国家流感中心推荐的分型方法,对2009年甲型H1N1流感大流行期间因流感样症状来首都儿科研究所附属儿童医院就诊患儿的咽拭子标本进行流感病毒核酸检测.结果 2009年6月1日至2010年2月28日期间共检测了4363份咽拭子标本,其中623例为甲型H1N1阳性,阳性率为14.3%,657例为其他甲型流感病毒阳性(15.1%),所有甲型流感病毒的总阳性率为29.3%.623例中有23例为危重症病例(占阳性患者的3.7%),其中5例死亡.618例信息完整的甲型H1N1病例中,患儿年龄为14天～16岁,性别比例为男比女为1.3:1.1～3岁儿童占25.2%,3～6岁学龄前儿童和6～12岁学龄儿童所占比例相近,各约占30%.在监测期间,仅呈现了一个甲型H1N1的流行波.2009年11月达到最高峰,随后减弱,2010年2月快速下降至2.7%.对监测期间每周20～30份临床标本同时进行季节性流感的监测显示,季节性H3N2、甲型H1N1和乙型流感交替流行.呼吸道合胞病毒(RSV)在甲型H1N1流行趋势减缓后逐渐流行成为流行优势株.结论 2009年6月至2010年2月北京地区儿童中出现甲型H1N1的流行,主要累及学龄前和学龄儿童.季节性流感和RSV与甲型H1N1交替流行.     

Induction of inflammatory cytokines and toll-like receptors in human normal respiratory epithelial cells infected with seasonal H1N1, 2009 pandemic H1N1, seasonal H3N2, and highly pathogenic H5N1 influenza virus

Respiratory epithelial cells are one of main targets for infections caused by influenza viruses. Recently, the induction of proinflammatory cytokines and toll-like receptors (TLRs) in normal human bronchial/tracheal epithelial cells infected with seasonal H1N1, 2009 pandemic H1N1, seasonal H3N2, or highly pathogenic H5N1 influenza virus were studied to understand the pathogenesis and early immune responses. The cells were productively infected with the viruses. Among the inflammatory cytokines tested, interleukin (IL)-8 was predominantly induced in virus-infected cells. Among the chemokines tested, interferon-γ-inducible protein-10 (IP-10) and growth-related oncogene-α (GRO-α) were predominantly induced in virus-infected cells. TLR-5 was predominantly induced in cells infected with seasonal H1N1, pandemic H1N1, or H5N1 influenza virus, and TLR-3 was predominantly induced in cells infected with seasonal H3N2 influenza virus. Taken together, the results suggest that IL-8, IP-10, and GRO-α are predominantly induced in respiratory epithelial cells infected with influenza A viruses, and that TLR-5 and TLR-3 are involved in the stimulation of virus-infected respiratory epithelial cells.     

Pandemic H1N1 influenza virus causes a stronger inflammatory response than seasonal H1N1 influenza virus in ferrets

A 2009 H1N1 influenza virus pandemic, which had its origin in swine, caused severe illness and mortality in humans. Inflammatory responses may be responsible for pathogenesis caused by infection with influenza viruses. To better understand the pathogenic mechanism, clinical signs and inflammatory responses in ferrets infected with the pandemic H1N1 were compared with those caused by seasonal H1N1 influenza virus. Ferrets infected with the 2009 pandemic H1N1 virus displayed higher body temperatures, greater reduction in body weight, and higher viral titers in the tracheae and lungs. Levels of inflammatory cytokines, including interleukin-6, interferon-alpha, and tumor necrosis factor-alpha, were higher in the lungs of ferrets infected with the 2009 pandemic H1N1. The data support the idea that increased pathogenesis caused by the 2009 pandemic H1N1 influenza virus may have been partially mediated by a higher induction of pro-inflammatory cytokines in the lungs of affected humans or animals.     

Prevalence of antibodies against seasonal influenza A and B viruses in children in Netherlands

To gain insight into the age at which children become infected with influenza viruses for the first time, we analyzed the seroprevalence of antibodies against influenza viruses in children 0 to 7 years of age in the Netherlands. Serum samples were collected during a cross-sectional population-based study in 2006 and 2007 and were tested for the presence of antibodies against influenza A/H1N1, A/H3N2, and B viruses representative of viruses present in previous influenza seasons using the hemagglutination inhibition assay. The seroprevalence of antibodies to influenza virus was higher in children 1 to 6 months of age than in children 7 to 12 months of age, which likely reflects the presence of maternally derived antibodies. The proportion of study subjects >1 year of age with detectable antibodies against influenza viruses gradually increased with age until they reached the age of 6 years, when they all had antibodies to at least one influenza A virus. These findings may have implications for the development of vaccination strategies aiming at the protection of young children against seasonal and/or pandemic influenza virus infection.     

Contemporary seasonal influenza A (H1N1) virus infection primes for a more robust response to split inactivated pandemic influenza A (H1N1) Virus vaccination in ferrets

Human influenza pandemics occur when influenza viruses to which the population has little or no immunity emerge and acquire the ability to achieve human-to-human transmission. In April 2009, cases of a novel H1N1 influenza virus in children in the southwestern United States were reported. It was retrospectively shown that these cases represented the spread of this virus from an ongoing outbreak in Mexico. The emergence of the pandemic led to a number of national vaccination programs. Surprisingly, early human clinical trial data have shown that a single dose of nonadjuvanted pandemic influenza A (H1N1) 2009 monovalent inactivated vaccine (pMIV) has led to a seroprotective response in a majority of individuals, despite earlier studies showing a lack of cross-reactivity between seasonal and pandemic H1N1 viruses. Here we show that previous exposure to a contemporary seasonal H1N1 influenza virus and to a lesser degree a seasonal influenza virus trivalent inactivated vaccine is able to prime for a higher antibody response after a subsequent dose of pMIV in ferrets. The more protective response was partially dependent on the presence of CD8(+) cells. Two doses of pMIV were also able to induce a detectable antibody response that provided protection from subsequent challenge. These data show that previous infection with seasonal H1N1 influenza viruses likely explains the requirement for only a single dose of pMIV in adults and that vaccination campaigns with the current pandemic influenza vaccines should reduce viral burden and disease severity in humans.     

Pathogenesis of emerging avian influenza viruses in mammals and the host innate immune response

Summary: Influenza A viruses of avian origin represent an emerging threat to human health as the progenitors of the next influenza pandemic. In recent years, highly pathogenic avian influenza H5N1 viruses have caused unprecedented epizootics on three continents and rare but highly fatal disease among humans exposed to diseased birds. Avian viruses of the H7 and H9 subtypes have also infected humans but generally resulted in far milder disease, yet they too should be considered as possible pandemic threats. Influenza virus infection elicits a complex network of host immune responses that, in uncomplicated influenza, results in effective control of the virus and the development of long-term memory responses. However, fatal avian H5N1 virus infection in both humans and experimental mammalian models is characterized by a high viral load in the respiratory tract, peripheral leukopenia and lymphopenia, a massive infiltration of macrophages into the lung, and dysregulation of cytokine and chemokine responses. This review focuses on avian influenza viruses as a pandemic threat, their induction of host innate immune responses in mammalian species, and the contribution of these responses to the disease process.     

A novel H1N1 virus causes the first pandemic of the 21st century

A novel H1N1 virus of swine origin (H1N1v ) is currently spreading in humans, giving rise to the first pandemic in 40 years. The disease is of moderate severity but has notable differences from seasonal influenza. In contrast to seasonal influenza, those over 60 years are relatively spared, a likely consequence of the presence of H1N1v cross‐neutralizing antibody in this age group. Most patients appear to have mild influenza‐like illness and many of the complications leading to hospitalization and mortality occur in those with underlying disease conditions or pregnancy. Studies in animal models suggest that the novel H1N1v pandemic virus causes a more severe illness and appears to have a greater predilection for the alveolar epithelium than seasonal influenza viruses. As there are as yet little data on the pathogenesis and immunology of H1N1v infection in humans, we have reviewed relevant data from past pandemics, from seasonal influenza and avian influenza H5N1 to highlight key issues pertaining to pathogenesis and immunology.     

Humans and Ferrets with Prior H1N1 Influenza Virus Infections Do Not Exhibit Evidence of Original Antigenic Sin after Infection or Vaccination with the 2009 Pandemic H1N1 Influenza Virus

The hypothesis of original antigenic sin (OAS) states that the imprint established by an individual''s first influenza virus infection governs the antibody response thereafter. Subsequent influenza virus infection results in an antibody response against the original infecting virus and an impaired immune response against the newer influenza virus. The purpose of our study was to seek evidence of OAS after infection or vaccination with the 2009 pandemic H1N1 (2009 pH1N1) virus in ferrets and humans previously infected with H1N1 viruses with various antigenic distances from the 2009 pH1N1 virus, including viruses from 1935 through 1999. In ferrets, seasonal H1N1 priming did not diminish the antibody response to infection or vaccination with the 2009 pH1N1 virus, nor did it diminish the T-cell response, indicating the absence of OAS in seasonal H1N1 virus-primed ferrets. Analysis of paired samples of human serum taken before and after vaccination with a monovalent inactivated 2009 pH1N1 vaccine showed a significantly greater-fold rise in the titer of antibody against the 2009 pH1N1 virus than against H1N1 viruses that circulated during the childhood of each subject. Thus, prior experience with H1N1 viruses did not result in an impairment of the antibody response against the 2009 pH1N1 vaccine. Our data from ferrets and humans suggest that prior exposure to H1N1 viruses did not impair the immune response against the 2009 pH1N1 virus.     

Seroprevalence to Influenza A(H1N1) 2009 Virus—Where Are We?

Age-specific seroprevalences for influenza virus make important contributions to estimating the burden of infection and determining the vulnerable populations. It is especially difficult to know the true clinical attack rates of the 2009 influenza A(H1N1) pandemic; however, we can estimate infection rates through analyses of seroprevalences based on national studies from different continents and countries with different demographics. After the 2009 influenza A(H1N1) pandemic, seroprevalence studies found 5 to 60% of populations across different continents and age groups having antibodies against the A(H1N1) 2009 virus. The seropositivity was highest in children and teenagers (20 to 60%) as well as in the elderly older than 80 years (20 to 40%). Preexisting cross-reactive antibodies against the virus were present mostly in sera of older people (born before 1950) who could have encountered viruses descended from the 1918 pandemic viruses. Experience with the 2009 pandemic indicates how essential early and timely serology data against the emerging virus can be for informing decisions on use of antivirals and vaccination campaigns, especially in regard to risk groups. The objectives of this review were to summarize the current data available on seroprevalence before and after the 2009 influenza A(H1N1) pandemic and the lessons learned for future pandemic preparedness.     

Information of the Center for Ecology and Epidemiology of Influenza, D. I. Ivanovsky Research Institute of Virology, Russian Academy of Medical Sciences, on the results of the 2009-2010 influenza and acute respiratory viral infection epidemic season (at week 40 of 2009 to week 22 of 2010) in the world and Russia

The paper describes the specific features of the 2009-2010 epidemic season in Russia and the world, which are due to the wide spread of a new pandemic strain of influenza A(H1N1)v virus. There is an unusual early upsurge in the incidence of influenza and acute respiratory viral infection (ARVI) (in October-November 2009) with its peak at weeks 45 to 48 of the year with a succeeding reduction to the seasonal values by its end. The circulation of influenza B virus strains was recorded in February-April 2010, which was responsible for the higher epidemic thresholds of morbidity in a number of Russia's regions. A study of the antigenic properties of the strains defined their relationship to the reference strains A/California/07/2009 (H1N1)v and B/Brisbene/60/2008. There were strains with amino acid substitutions at position 222 of hemagglutinin in the population of pandemic influenza A(H1N1)v virus. The strains of the new pandemic influenza A(H1N1)v virus were resistant to remantadine and susceptible to oseltamivir, zanamivir, and arbidol. The influenza B virus strains were susceptible to oseltamivir, zanamivir, and arbidol. The proportion of pathogens of some ARVIs was as follows: parainfluenza viruses, 9.8%; adenoviruses, 5.5%; respiratory syncytial virus, 4.8%; and Mycoplasma pneumonia, 0.6%. There is evidence that there is a need for further monitoring of influenza viruses in Russia.     

Cellular response to influenza virus infection: a potential role for autophagy in CXCL10 and interferon-alpha induction

Historically, influenza pandemics have arisen from avian influenza viruses. Avian influenza viruses H5N1 and H9N2 are potential pandemic candidates. Infection of humans with the highly pathogenic avian influenza H5N1 virus is associated with a mortality in excess of 60%, which has been attributed to dysregulation of the cytokine system. Human macrophages and epithelial cells infected with some genotypes of H5N1 and H9N2 viruses express markedly elevated cytokine and chemokine levels when compared with seasonal influenza A subtype H1N1 virus. The mechanisms underlying this cytokine and chemokine hyperinduction are not fully elucidated. In the present study, we demonstrate that autophagy, a tightly regulated homeostatic process for self-digestion of unwanted cellular subcomponents, plays a role in cytokine induction. Autophagy is induced to a greater extent by H9N2/G1, in association with cytokine hyperinduction, compared with H1N1 and the novel pandemic swine-origin influenza A/H1N1 viruses. Using 3-methyladenine to inhibit autophagy and small interfering RNA to silence the autophagy gene, Atg5, we further show that autophagic responses play a role in influenza virus-induced CXCL10 and interferon-α expression in primary human blood macrophages. Our results provide new insights into the pathogenic mechanisms of avian influenza viruses.     

Respiratory viral infections during the 2009–2010 winter season in Central England, UK: incidence and patterns of multiple virus co-infections

Acute viral respiratory infections are the most common infections in humans. Co-infection with different respiratory viruses is well documented but not necessarily well understood. The aim of this study was to utilise laboratory data from the winter season following the 2009 influenza A(H1N1) outbreak to investigate rates of respiratory virus co-infections, virus prevalence in different age groups and temporal variations in virus detection. The Health Protection Agency Public Health Laboratory (HPA PHL) Birmingham, UK, routinely uses polymerase chain reaction (PCR) to detect common respiratory viruses. The results from specimens received for respiratory virus investigations from late September 2009 to April 2010 were analysed. A total of 4,821 specimen results were analysed. Of these, 323 (13.2?%) had co-detections of two viruses, 22 (0.9?%) had three viruses and four (0.2?%) had four viruses. Reciprocal patterns of positive or negative associations between different virus pairs were found. Statistical analysis confirmed the significance of negative associations between influenza A and human metapneumovirus (HMPV), and influenza A and rhinovirus. Positive associations between parainfluenza with rhinovirus, rhinovirus with respiratory syncytial virus (RSV) and adenovirus with rhinovirus, parainfluenza and RSV were also significant. Age and temporal distributions of the different viruses were typical. This study found that the co-detection of different respiratory viruses is not random and most associations are reciprocal, either positively or negatively. The pandemic strain of influenza A(H1N1) was notable in that it was the least likely to be co-detected with another respiratory virus.     

Receptor specificity of subtype H1 influenza A viruses isolated from swine and humans in the United States

The evolution of classical swine influenza viruses receptor specificity preceding the emergence of the 2009 H1N1 pandemic virus was analyzed in glycan microarrays. Classical swine influenza viruses from the α, β, and γ antigenic clusters isolated between 1945 and 2009 revealed a binding profile very similar to that of 2009 pandemic H1N1 viruses, with selectivity for α2-6-linked sialosides and very limited binding to α2-3 sialosides. Despite considerable genetic divergence, the ‘human-like’ H1N1 viruses circulating in swine retained strong binding preference for α2-6 sialylated glycans. Interspecies transmission of H1N1 influenza viruses from swine to humans or from humans to swine has not driven selection of viruses with distinct novel receptor binding specificities. Classical swine and human seasonal H1N1 influenza viruses have conserved specificity for similar α2-6-sialoside receptors in spite of long term circulation in separate hosts, suggesting that humans and swine impose analogous selection pressures on the evolution of receptor binding function.