Research Article

Full Genomic Sequences of H5N1 Highly Pathogenic Avian Influenza Virus in Human Autopsy Specimens Reveal Genetic Variability and Adaptive Changes for Growth in MDCK Cell Cultures

Table 4

Analysis for virulence determinants of H5N1 HPAI virus in this study compared to the H5N1 genetic change inventory.

ProteinAmino acid mutation previously reportedAssociation and functionAmino acid observed in autopsy/culture

PB2I63TDecreased pathogenicity in mice63I
E627KIncreased replication efficiency in cell culture and enhanced virulence in mice627K
Enhanced polymerase activity and mammalian host adaptation
Mammalian host adaptation, increased virulence in mice
Enhanced polymerase activity
H5 virus transmissible among ferrets
M28I, A274T, K526R, I553V, L607VDecreased polymerase activity28M, 274A,526K, 553I, 607L
L89V, G309D, T339K, R477G, I495V, A676TEnhanced polymerase activity, increased virulence in mice89V, 309D, 339K, 477G, 495V, 676T
PB1K207RDecreased polymerase activity in mammalian cells207K
Y436HDecreased polymerase activity and virulence in mallards, ferrets, and mice436Y
T677MDecreased virulence in mice677T
V3A, N328K, N375SDecreased replication efficiency and virulence in ferrets3V, 328N, 375N
V473L, P598LDecreased polymerase activity and replication efficiency473V, 598L
PAP149S, R266H, K357I, T515SDecreased polymerase activity in mammalian cells149S, 266R, 357I, 515T
NA49-68 deletionEnhanced virulence in mice49-68 deletion
M1N30D, T139A, T215AIncreased virulence in mice30D, 139T, 215A
M2L26F, V27A, G34E, A30V/T/S, S31N/GReduced susceptibility to amantadine and rimantadine26I, 27V, 34G, 30A, 31 N
NS180-84 deletion, P42S, D87E, L98F, L101MIncreased virulence in mice80-84 deletion,42S, 87D, 98F, 101M
ESEV (in PDZ domain)Increased virulence in miceESEV(in PDZ domain)