Article

Transmission of influenza A/H5N1 viruses in mammals

Influenza Virus Research Center, National Institute of Infectious Diseases, Musashimurayama, Tokyo 208-0011, Japan.
Virus Research (Impact Factor: 2.83). 08/2013; 178. DOI: 10.1016/j.virusres.2013.07.017
Source: PubMed

ABSTRACT Highly pathogenic avian H5N1 influenza A viruses occasionally infect humans and cause severe respiratory disease and fatalities. Currently, these viruses are not efficiently transmitted from person to person, although limited human-to-human transmission may have occurred. Nevertheless, further adaptation of avian H5N1 influenza A viruses to humans and/or reassortment with human influenza A viruses may result in aerosol transmissible viruses with pandemic potential. Although the full range of factors that modulate the transmission and replication of influenza A viruses in humans are not yet known, we are beginning to understand some of the molecular changes that may allow H5N1 influenza A viruses to transmit via aerosols or respiratory droplets among mammals. A better understanding of the biological basis and genetic determinants that confer transmissibility to H5N1 influenza A viruses in mammals is important to enhance our pandemic preparedness.

1 Follower
 · 
96 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Two ferret-adapted H5N1 viruses capable of respiratory droplet transmission have been reported with mutations in the hemagglutinin receptor-binding site and stalk domains. Glycan microarray analysis reveals that both viruses exhibit a strong shift towards binding to 'human-type' α2-6 sialosides, but with notable differences in fine specificity. Crystal structure analysis further shows that the stalk mutation causes no obvious perturbation of the receptor-binding pocket, consistent with its impact on hemagglutinin stability without effecting receptor specificity.
    Journal of Virology 10/2013; 88(1). DOI:10.1128/JVI.02690-13 · 4.65 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The best approach to control the spread of influenza virus during a pandemic is vaccination. Yet, an appropriate vaccine is not available early in the pandemic since vaccine production is time consuming. For influenza strains with a high pandemic potential like H5N1, stockpiling of vaccines has been considered but is hampered by rapid antigenic drift of the virus. It has, however, been shown that immunization with a given H5N1 strain can prime the immune system for a later booster with a drifted variant. Here, we investigated whether whole inactivated virus (WIV) vaccine can be processed to tablets suitable for sublingual (s.l.) use and whether s.l. vaccine administration can prime the immune system for a later intramuscular (i.m.) boost with a heterologous vaccine. In vitro results demonstrate that freeze-drying and tableting of WIV did not affect the integrity of the viral proteins or the hemagglutinating properties of the viral particles. Immunization experiments revealed that s.l. priming with WIV (prepared from the H5N1 vaccine strain NIBRG-14) 4 weeks prior to i.m. booster immunization with the same virus strongly enhanced hemagglutination-inhibition (HI) titers against NIBRG-14 and the drifted variant NIBRG-23. Moreover, s.l. (and i.m.) immunization with NIBRG-14 also primed for a subsequent heterologous i.m. booster immunization with NIBRG-23 vaccine. In addition to HI serum antibodies, s.l. priming enhanced lung and nose IgA responses, while i.m. priming enhanced lung IgA but not nose IgA levels. Our results identify s.l. vaccination as a user-friendly method to prime for influenza-specific immune responses toward homologous and drifted variants.
    The AAPS Journal 01/2014; 16(2). DOI:10.1208/s12248-014-9565-z · 3.91 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: AimsTo estimate qualitatively the probabilities of release (or entry) of Eurasian lineage H5N1 highly pathogenic avian influenza (HPAI) virus into Great Britain (GB), the Netherlands and Italy through selected higher risk species of migratory water bird. Methods and ResultsThe probabilities of one or more release events of H5N1 HPAI per year (prelease) were estimated qualitatively for 15 avian species, including swans, geese, ducks and gulls, by assessing the prevalence of H5N1 HPAI in different regions of the world (weighted to 2009) and estimates of the total numbers of birds migrating from each of those regions. The release assessment accommodated the migration times for each species in relation to the probabilities of their surviving infection and shedding virus on arrival. Although the predicted probabilities of release of H5N1 per individual bird per year were low, very low or negligible, prelease was high for a few species reflecting the high numbers of birds migrating from some regions. Values of prelease were generally higher for the Netherlands than for GB, while ducks and gulls from Africa presented higher probabilities to Italy compared to the Netherlands and GB. Conclusions Bird species with high values of prelease in GB, the Netherlands and Italy generally originate from within Europe based on data for global prevalence of H5N1 between 2003 and 2009 weighted to 2009. Potential long distance transfer of H5N1 HPAI from North Asia and Eurasia to GB, the Netherlands and Italy is limited to a few species and does not occur from South East Asia, an area where H5N1 is endemic. Significance and Impact of the StudyThe approach accommodates bio-geographic conditions and variability in the estimated worldwide prevalence of the virus. The outputs of this release assessment can be used to inform surveillance activities through focusing on certain species and migratory pathways.This article is protected by copyright. All rights reserved.
    Journal of Applied Microbiology 03/2014; 116(6). DOI:10.1111/jam.12489 · 2.39 Impact Factor
Show more