Table. Summary of molecular markers identified in influenza virus strains from South America in study of highly pathogenic avian influenza A(H5N1) from wild birds, poultry, and mammals, Peru*.

Protein	Mutation/motif	Phenotype
PB2	D9N†	Increases virulence in mice
	L89V, G309D, T339K, R477G, I495V, K627E, A676T	Increases polymerase activity in mammalian cell lines and increases virulence in mice
	Q591K‡	Increases polymerase activity in mammalian and avian cell lines, increases replication in mammalian cell lines, increases virulence in mice
	D701N‡	Increases polymerase activity, enhances replication efficiency, increases virulence and contact transmission in guinea pigs, increases virulence in mice
PB1	D3V	Increases polymerase activity and viral replication in avian and mammalian cell lines
	D622G	Increases polymerase activity and virulence in mice
PB1-F2	N66S	Enhances replication, virulence, and antiviral response in mice
PA	N383D	Increases polymerase activity in mammalian and avian cell lines
HA	D94N,§ S133A, S154N	Increases virus binding to α2–6 receptor
	T156A	Increases virus binding to α2–6, increases transmission in guinea pigs
	S107R, T108I	Increases virulence in chickens and mice and the pH of fusion
	K218Q, S223R	Increases virus binding to α2–3 and α2–6 receptors
	321-329 (PLR(EorG)KRRKR)	Polybasic cleavage motif sequence required for HPAIV
NP	M105V¶	Increases virulence in chickens
	I109T#	Increases polymerase activity and viral replication in chickens (but not ducks), increases virulence in chickens
	A184K	Increases replication in avian cells and virulence in chickens
M1	N30D	Increases virulence in mice
	I43M	Increases virulence in mice, chickens and ducks
	T215A	Increases virulence in mice
M2	I27A**	Increases resistance to amantadine and rimantadine
NS1	P42S	Increases virulence and decreases the antiviral response in mice
	C138F	Increases replication in mammalian cell and decreases the interferon response
	V149A	Increases virulence and decreases the interferon response in chickens
	L103F, I106M	Increases virulence in mice
	K55E, K66E, C138F	Enhances replication in mammalian cells and decreases the interferon response

*Molecular markers of influenza virus strains were identified as previously described (9). HA, hemagglutinin; HPAIV, highly pathogenic avian influenza virus; M1, matrix protein 1; M2, matrix protein 2; NP, nucleoprotein; NS1, nonstructural protein 1. †Only in 2 sequences from pelicans (GISAID [https://www.gisaid.org] accession nos. EPI_ISL_17099964, EPI_ISL_17165223). ‡Only in sequences from 2 sea lions in Peru and 1 human case in Chile. §Only in 1 sequence from a wild bird in Peru (GISAID accession no. EPI_ISL_17660074). ¶Mutation sequences from Venezuela and Colombia (Choco) have M rather than V. #Only in sequences from Colombia (Choco). **Only in 1 sequence from a wild bird in Peru (GISAID accession no. EPI_ISL_17777528).