Host adaptation and transmission of influenza A viruses in mammals

Figures & data

Table 1 Zoonotic influenza A viruses affecting humans

Influenza A virus subtype	Number of confirmed human cases	Number of deaths	Airborne transmission between mammals	Subtype able to transmit between humans
Avian H5 (H5N1)	661 ^Citation13	387	Y ^Citation14,Citation15,Citation16	N
Avian H7 (H7N2, H7N3, H7N7, H7N9)	240 ^Citation13,Citation17,Citation18,Citation19,Citation20,Citation21	46	Y ^Citation22,Citation23,Citation24,Citation25	N
Avian H9 (H9N2)	5 ^Citation26,Citation27,Citation28	0	Y ^Citation29	N
Avian H6 (H6N1)	1 ^Citation30	0	ND^a	N
Avian H10 (H10N7)	2 ^Citation31	0	ND	N
Swine H3	348^b ^Citation32	0	Y ^Citation33	Y
Swine H1 (H1N1, H1N2)	21^b ^Citation32	0	Y ^Citation34	Y

a ND, not determined.

b Reported since 2005.

Table 2 Molecular signatures in avian influenza viruses (possibly) affecting airborne transmission between ferrets

Study	Influenza virus	Protein	Mutations
Sorrell et al.^Citation29	H9N2 (Human H3N2 backbone)	HA	HA T189A^a–Q226L–G192R (HA2)
		NA	I28V^b
Imai et el.^Citation14	H5 (A(H1N1)pdm09 backbone)	HA	N158D–N220K–Q226L–T315I
Herfst et al.^Citation15	H5N1	HA	H110Y^c–T160A^c–Q226L^c–G228S^c
		PB2	E627K^c
		PB1	H99Y–I368V
		NP	R99K–S345N
Chen et al.^Citation97	H5 (Human H3N2 NA)	HA	Q192R–Q226L–G228S

a All HA mutations are in H3 numbering.

b N2 numbering.

c Five amino-acid substitutions were consistently detected in airborne-transmissible virus isolates.

Figure 1 Traits important for airborne transmission of influenza virus between mammals. Increased binding of HA to appropriate cells of the URT of mammalian host cells contributes to the airborne transmissibility. Increased acid stability of the HA was also observed in airborne transmissible virus. Adaptation of the polymerase complex is necessary to facilitate increased replication in the mammalian host cell and is a likely determinant of airborne transmissibility. Although this has not (yet) been shown directly, the release of single viral particles instead of aggregates may aid the airborne transmissibility of the virus, which may be regulated by the HA–NA balance. Virus attachment and budding images were described previously.¹²³ Fusion and replication data are unpublished. The fusion picture is hypothetical and shows a non-adapted HA with a high pH threshold for fusion and an adapted HA with a decreased pH threshold for fusion. The replication figure contains data of the Indonesia/5/05 polymerase complex and Indonesia/5/05 airborne transmissible polymerase complex by Herfst et al.¹⁵

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