Predicting ‘airborne’ influenza viruses: (trans-) mission impossible?
Highlights
► Airborne transmission is the main mode for influenza virus transmission between humans. ► Viral, host, and environmental factors driving airborne transmission are largely unknown and difficult to elucidate. ► Pandemic influenza viruses acquired airborne transmission via reassortment with human strains and mutations in avian-derived virus genes. ► Virus attachment, replication, release and aerosolization are postulated to represent key factors for emergence of pandemic influenza viruses. ► To predict future influenza pandemics, increasing our understanding of airborne virus transmission is crucial.
Introduction
The virus or virus subtype that will cause the next influenza pandemic is a highly debated topic in the field. Some believe that only influenza virus subtypes H1, H2, and H3 can cause pandemics in humans, and therefore — beyond isolated cases of zoonotic infections — we should not worry about virus subtypes such as H5N1, H7N7 or H9N2 for human health. Many believe that swine viruses, rather than avian viruses, are more likely to cause the next pandemic. However, beyond the fact that there will be future pandemics, there is little known in terms of the viral origin, subtype, and virulence of the next pandemic. One other assumption can be made: the virus will be transmissible via small particle aerosols (typically <5 μm) or large respiratory droplets (typically >5 μm), shortened hereafter as airborne transmissible.
Influenza A viruses are constantly undergoing genetic and phenotypic changes during their circulation in avian and mammalian species. Our knowledge of viral traits necessary for host switching and virulence has increased significantly over the last decade. However, what exactly determines airborne transmission of influenza viruses in humans has remained largely unknown. Only when we fully understand the viral (genetic and phenotypic), host, and environmental factors that drive airborne transmission can we start to make predictions about which influenza viruses may cause future influenza pandemics.
Section snippets
Past pandemics
Four major pandemics have been recognized for which viral genome sequence data is available. While it was initially proposed that the 1918 H1N1 Spanish influenza pandemic was caused by a wholly avian virus that adapted to humans [1], recent evidence suggests that some of its genes were derived from mammalian viruses circulating as early as 1911 [2•]. The 1957 H2N2 Asian influenza pandemic resulted from the reassortment of avian HA, NA, and PB1 virus genes with the then circulating seasonal
Viral determinants of transmission
Retrospective analysis of pandemic H1 (1918), H2 and H3 viruses has revealed that only one to two mutations in the HA receptor binding site are required to confer binding preference for virus receptors on cells of the upper respiratory tract (URT) of humans, α2,6-linked sialic acids (SAs) [7]. Partially borrowing from this knowledge, several mutations in the HA protein, including Q222L, G224S, E186D, K189R, S223N and N182K (H5 numbering), have been shown to change and/or increase receptor
Airborne transmission; size does matter
Human-to-human transmission of influenza viruses can occur through contact, direct or indirect, and/or respiratory droplets (large droplets and aerosols). Opinions differ on the importance of each mode of transmission (reviewed in [22, 23]). The role of each has been well studied in mammalian models, focusing on the ferret and guinea pig (reviewed in [24•] and Table 1). Efficient aerosolization of viral particles is, however, crucial for a virus with transmission efficiency and pandemic
H?N?, the next pandemic
The continuing spread of highly pathogenic avian influenza (HPAI) H5N1 viruses in poultry and the consistent, albeit infrequent, transmission to humans with high mortality rates [32, 33] has kept H5N1 a top candidate on the list of potential future pandemics. It has been suggested that human-to-human transmission between family members in close contact has occurred [34, 35, 36]; however, sustained human-to-human transmission has not been confirmed. It is this lack of human-to-human transmission
Virus design; why and how do influenza viruses become airborne?
The major challenges for influenza virus transmission research going forward are the types of studies needed to elucidate mechanisms for transmission. In our opinion, the focus should be on ‘gain of function’ approaches rather than ‘loss of function’. For the purpose of virus transmission studies, loss of function experiments is like destroying a car engine; remove any crucial part and the engine will stop running. In analogy, mutating a transmissible virus so it no longer transmits is a
References and recommended reading
Papers of particular interest, published within the period of review, have been highlighted as:
• of special interest
•• of outstanding interest
Acknowledgements
The authors thank Debby van Riel for providing Figure 2A and B. The research of the authors is sponsored under contract HHSN266200700010C from National Institutes of Health/National Institute of Allergy and Infectious Diseases (NIH/NIAID). M.G. is a Marie Curie fellow and funded under contract PIEF-GA-2009-237505.
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A review on airborne microorganisms in particulate matters: Composition, characteristics and influence factors
2018, Environment InternationalCitation Excerpt :For viral perniciousness and infection, more researchers have paid attention to airborne virus' investigations. Particle size can determine physical stability of aerosols, the sites of deposition and the degree of retention, and size of viral aerosols is an immense significance because they may cause human virus infections and affect viral personal size, survivability, pathogenicity rate and even meteorological conditions (Hogan et al., 2005; Sorrell et al., 2011). Small doses of respiratory viruses given by small particle aerosol were infective, and airborne viruses' transmission was most consistent with transmission of small particle aerosol, and these evidenced that particle size played a vital role in viral spread and infection, especially small size (Knight, 1970).