Influenza A virus transmission via respiratory aerosols or droplets as it relates to pandemic potential

Abstract

Many respiratory viruses of humans originate from animals. For instance, there are now eight paramyxoviruses, four coronaviruses and four orthomxoviruses that cause recurrent epidemics in humans but were once confined to other hosts. In the last decade, several members of the same virus families have jumped the species barrier from animals to humans. Fortunately, these viruses have not become established in humans, because they lacked the ability of sustained transmission between humans. However, these outbreaks highlighted the lack of understanding of what makes a virus transmissible. In part triggered by the relatively high frequency of occurrence of influenza A virus zoonoses and pandemics, the influenza research community has started to investigate the viral genetic and biological traits that drive virus transmission via aerosols or respiratory droplets between mammals. Here we summarize recent discoveries on the genetic and phenotypic traits required for airborne transmission of zoonotic influenza viruses of subtypes H5, H7 and H9 and pandemic viruses of subtypes H1, H2 and H3. Increased understanding of the determinants and mechanisms of respiratory virus transmission is not only key from a basic scientific perspective, but may also aid in assessing the risks posed by zoonotic viruses to human health, and preparedness for such risks.

Keywords: emerging disease; ferret; guinea pig; host range; pandemic.

Graphical Abstract Figure.

This review summarizes recent discoveries on the genetic and phenotypic traits required for airborne transmission of zoonotic influenza viruses of subtypes H5, H7 and H9 and pandemic viruses of subtypes H1, H2 and H3.

Figure 1.

Paramyxovirus, coronavirus and influenza virus hosts. Original reservoirs for influenza viruses (blue), paramyxoviruses (red) and coronaviruses (green) are shown in the center of the figure in black. Recent studies have placed bats as tentative hosts at ancestral nodes to both major Paramyxoviridae subfamilies (Paramyxovirinae and Pneumovirinae) (Drexler et al. 2012). Moreover, bats host the broadest diversity of coronaviruses including close relatives of humans coronaviruses, supporting the zoonotic origin of several humans coronaviruses (Vijaykrishna et al. ; Drexler, Corman and Drosten 2014). Birds have also been suggested to be the gene pool of group 3 coronaviruses (Woo et al. 2009). The presence of influenza viruses in both waterfowl and bats suggested that transmission from birds to bats may have occurred in the past (illustrated with the arrow between the two host groups). As humans come rarely into contact with bats and waterfowl, they are more likely to become infected with zoonotic viruses via intermediate hosts, such as domestic birds or mammals. Usually, these zoonotic events are restricted to isolated cases of human infection with no onward transmission between humans subsequently. Rarely, upon mutation or reassortment, zoonotic viruses adapt to become human-to-human transmissible, and may start a pandemic and become endemic in humans. Numerous viruses of animal origin are endemic in humans (outer circle). Four influenza pandemics have occurred in the last century. RSV: respiratory syncytial virus; HMPV : human metapneumovirus; PIV: parainfluenza virus; MERS: Middle-East Respiratory Syndrome; SARS: Severe Acute Respiratory Syndrome.

Figure 2.

Potential routes of transmission and adaptation of influenza viruses. Many scenarios could support the transmission of influenza viruses from their original reservoir to humans and subsequent adaption to transmit via the airborne route: (i) direct transmission from waterfowl to humans and subsequent adaptation in humans; (ii) transmission from waterfowl to intermediate hosts, adaptation in these hosts and subsequent transmission to humans; and (iii) reassortment in intermediate hosts of influenza viruses originating from diverse animals species and transmission to humans.

Figure 3.

Substitutions associated with airborne transmission of H5N1 influenza virus between ferrets. Cartoon representation of the HA structure of A/Vietnam/1203/04 H5N1 influenza A virus (protein database code 4KDO). The ribbon structure of one HA monomer is colored in green, the fusion peptide and vestigial esterase subdomain are depicted in orange and yellow, respectively. The human receptor analog, LSTc, depicted in pink is docked into the RBS. The amino acid substitutions described by Herfst et al. are highlighted in red, and the mutations of Imai et al. in blue. Substitution Q226L was described by both groups. Substitutions T160A and N158D, H110Y and T318I, and Q226L/G228S and N224K/Q226L are thought to be functionally equivalent.