Concept: Influenza A virus subtype H5N1
Highly pathogenic avian H5N1 influenza A viruses occasionally infect humans, but currently do not transmit efficiently among humans. The viral haemagglutinin (HA) protein is a known host-range determinant as it mediates virus binding to host-specific cellular receptors. Here we assess the molecular changes in HA that would allow a virus possessing subtype H5 HA to be transmissible among mammals. We identified a reassortant H5 HA/H1N1 virus-comprising H5 HA (from an H5N1 virus) with four mutations and the remaining seven gene segments from a 2009 pandemic H1N1 virus-that was capable of droplet transmission in a ferret model. The transmissible H5 reassortant virus preferentially recognized human-type receptors, replicated efficiently in ferrets, caused lung lesions and weight loss, but was not highly pathogenic and did not cause mortality. These results indicate that H5 HA can convert to an HA that supports efficient viral transmission in mammals; however, we do not know whether the four mutations in the H5 HA identified here would render a wholly avian H5N1 virus transmissible. The genetic origin of the remaining seven viral gene segments may also critically contribute to transmissibility in mammals. Nevertheless, as H5N1 viruses continue to evolve and infect humans, receptor-binding variants of H5N1 viruses with pandemic potential, including avian-human reassortant viruses as tested here, may emerge. Our findings emphasize the need to prepare for potential pandemics caused by influenza viruses possessing H5 HA, and will help individuals conducting surveillance in regions with circulating H5N1 viruses to recognize key residues that predict the pandemic potential of isolates, which will inform the development, production and distribution of effective countermeasures.
Severe disease in humans caused by a novel influenza A virus that is distinct from circulating human influenza A viruses is a seminal event. It might herald sporadic human infections from an animal source - e.g., highly pathogenic avian influenza (HPAI) A (H5N1) virus; or it might signal the start of an influenza pandemic - e.g., influenza A(H1N1)pdm09 virus. Therefore, the discovery of novel influenza A (H7N9) virus infections in three critically ill patients reported in the Journal by Gao and colleagues is of major public health significance. Chinese scientists are to be congratulated for the apparent speed with which . . .
The prevalence of avian H5N1 influenza A infections in humans has not been definitively determined. Cases of H5N1 infection in humans confirmed by the World Health Organization (WHO) are fewer than 600 in number, with an overall case fatality rate of >50%. We hypothesize that the stringent criteria for confirmation of a human case of H5N1 by WHO do not account for a majority of infections but rather the select few hospitalized cases that are more likely to be severe and result in poor clinical outcome. Meta-analysis shows that 1 to 2% of more than 12,500 study participants from 20 studies had seroevidence for prior H5N1 infection.
SUMMARY Within China’s Poyang Lake region, close interactions between wild migratory birds and domestic poultry are common and provide an opportunity for the transmission and subsequent outbreaks of highly pathogenic avian influenza (HPAI) virus. We overlaid a series of ecological factors associated with HPAI to map the risk of HPAI in relation to natural and anthropogenic variables, and we identified two hotspots for potential HPAI outbreaks in the Poyang Lake region as well as three corridors connecting the two hotspot areas. In hotspot I, there is potential for migratory birds to bring new avian influenza (AI) strains that can reassort with existing strains to form new AI viruses. Hotspot II features high-density poultry production where outbreaks of endemic AI viruses are likely. The three communication corridors that link the two hotspots further promote HPAI H5N1 transmission and outbreaks and lead to the persistence of AI viruses in the Poyang Lake region. We speculate that the region’s unevenly distributed poultry supply-and-demand system might be a key factor inducing HPAI H5N1 transmission and outbreaks in the Poyang Lake region.
The H5N1 avian influenza virus causes severe disease and high mortality, making it a major public health concern worldwide. The virus uses the host cellular machinery for several steps of its life cycle. In this report, we observed overexpression of the ubiquitin-like protein FAT10 following live H5N1 virus infection in BALB/c mice and in the human respiratory epithelial cell lines A549 and BEAS-2B. Further experiments demonstrated that FAT10 increased H5N1 virus replication and decreased the viability of infected cells. Total RNA extracted from H5N1 virus-infected cells, but not other H5N1 viral components, upregulated FAT10, and this process was mediated by the retinoic acid-induced protein I-NF-κB signaling pathway. FAT10 knockdown in A549 cells upregulated type I IFN mRNA expression and enhanced STAT1 phosphorylation during live H5N1 virus infection. Taken together, our data suggest that FAT10 was upregulated via retinoic acid-induced protein I and NF-κB during H5N1 avian influenza virus infection. And the upregulated FAT10 promoted H5N1 viral replication by inhibiting type I IFN.
During the early phase of the 2009 influenza pandemic, attempts were made to contain the spread of the virus. Success of reactive control measures may be compromised if the proportion of transmission that occurs before overt clinical symptoms develop is high. In this study we investigated the timing of transmission of an early prototypic strain of pandemic H1N1 2009 influenza virus in the ferret model. Ferrets are the only animal model in which this can be assessed because they display typical influenza-like clinical signs including fever and sneezing after infection. We assessed transmission from infected animals to sentinels that were placed either in direct contact or in adjacent cages, the latter reflecting the respiratory droplet (RD) transmission route. We found that pre-symptomatic influenza transmission occurred via both contact and respiratory droplet exposure before the earliest clinical sign, fever, developed. Three of 3 animals exposed in direct contact between day 1 and 2 after infection of the donor animals became infected, and 2/3 of the animals exposed at this time period by the RD route acquired the infection, with the third animal becoming seropositive indicating either a low level infection or significant exposure. Moreover, this efficient transmission did not temporally correlate with respiratory symptoms, such as coughs and sneezes, but rather with the peak viral titre in the nose. Indeed respiratory droplet transmission did not occur late in infection, even though this was when sneezing and coughing were most apparent. None of the 3 animals exposed at this time by the RD route became infected and these animals remained seronegative at the end of the experiment. These data have important implications for pandemic planning strategies and suggest that successful containment is highly unlikely for a human-adapted influenza virus that transmits efficiently within a population.
Highly pathogenic avian influenza virus (HPAI) strain H5N1 has had direct and indirect economic impacts arising from direct mortality and control programmes in over 50 countries reporting poultry outbreaks. HPAI H5N1 is now reported as the most widespread and expensive zoonotic disease recorded and continues to pose a global health threat. The aim of this research was to assess the potential of utilising Hazard Analysis of Critical Control Points (HACCP) assessments in providing a framework for a rapid response to emerging infectious disease outbreaks. This novel approach applies a scientific process, widely used in food production systems, to assess risks related to a specific emerging health threat within a known zoonotic disease hotspot. We conducted a HACCP assessment for HPAI viruses within Vietnam’s domestic poultry trade and relate our findings to the existing literature. Our HACCP assessment identified poultry flock isolation, transportation, slaughter, preparation and consumption as critical control points for Vietnam’s domestic poultry trade. Introduction of the preventative measures highlighted through this HACCP evaluation would reduce the risks posed by HPAI viruses and pressure on the national economy. We conclude that this HACCP assessment provides compelling evidence for the future potential that HACCP analyses could play in initiating a rapid response to emerging infectious diseases.
The novel influenza A H7N9 virus emerged recently in mainland China, whereas the influenza A H5N1 virus has infected people in China since 2003. Both infections are thought to be mainly zoonotic. We aimed to compare the epidemiological characteristics of the complete series of laboratory-confirmed cases of both viruses in mainland China so far.
ABSTRACT A voluntary 60-day pause on avian H5N1 influenza virus transmission research was announced in January 2012 by the international community of influenza scientists engaged in this work to provide time to explain the benefits of such work and the risk mitigation measures in place. Subsequently, the pause was extended to allow for time for review of the biosafety and biosecurity conditions. After almost 8 months, these conditions have been met in some countries and are close to being met in others. Because H5N1 virus transmission studies are essential for pandemic preparedness, researchers who have approval from their governments and institutions to conduct this research safely under appropriate biosecurity conditions should resume this important work.
ABSTRACT The voluntary moratorium on gain-of-function research related to the transmissibility of highly pathogenic H5N1 influenza virus should continue, pending the resolution of critical policy questions concerning the rationale for performing such experiments and how best to report their results. The potential benefits and risks of these experiments must be discussed and understood by multiple stakeholders, including the general public, and all decisions regarding such research must be made in a transparent manner.