Genetic evolution of H5N1 Jen-Ren Wang, Ph. D. • Department of Medical Laboratory Science and Biot echnology, National Cheng Kung University • Department of Pathology, National Cheng Kung Univ ersity Hospital • National Health Research Institutes Tainan Virolo gy Laboratory for Diagnosis and Research • Department of Health, Taiwan Centers for Disease Control contract Virology Laboratory
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Genetic evolution of H5N1 Jen-Ren Wang, Ph. D. Department of Medical Laboratory Science and Biotechnology, National Cheng Kung University Department of.
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Genetic evolution of H5N1
Jen-Ren Wang, Ph. D.
• Department of Medical Laboratory Science and Biotechnology,
National Cheng Kung University • Department of Pathology, National Cheng Kung University Ho
spital • National Health Research Institutes Tainan Virology Laborator
y for Diagnosis and Research • Department of Health, Taiwan Centers for Disease Control con
tract Virology Laboratory
World Health Organization 18/Mar/2008
Webster, et al. N ENGL J MED. 2006. 355:2174-2177.
Webster G, et al. N ENGL J MED. 2006. 355:2174-2177.
Genetic reassortment of H5N1 in Asia from 1999 to 2005
Peiris M. J. S. et al., 2007 Clin Microbiol Rev 20(2), 243–267.
Phylogenetic relationships of the HA and NP genes of influenza A viruses isolated in Indonesia and Vietnam
Smith GJ, et al. Virology. 2006. 5;350(2):258-68.
HA NP
Clade IClade II, subclade I
Smith GJ, et al. Virology. 2006. 5;350(2):258-68.
Smith GJ, et al. Virology. 2006. 5;350(2):258-68.
(Z)
(Z+V)
(Z)
(Z)(Z)
(Z+G)
(Z+G+W)
Genotypes of H5N1 influenza reassortants in Asia during 2003-2005
Chen et al., 2006 PNAS 103, 2845-2850.
Smith, G. J. D. et al. (2006) Proc. Natl. Acad. Sci. USA 103, 16936-16941
Emergence and predominance of an H5N1 variant in China since late
2005
Collection date No. of FJ-like viruses
2005
July–September 1/33 (3)
October–December 72/136 (53)
2006
January–March 90/113 (80)
April–June 103/108 (95)
Total 266/390 (68)
Smith, G. J. D. et al. (2006) Proc. Natl. Acad. Sci. USA 103, 16936-16941
Antigenetic analysis of different H5N1 lineages
FJ-like
GD06, QH-like, Mixed/VNM2
IDN
GY2VTM
GY1
Phylogenetic analysis of H5N1 HA gene from Europe, Africa, and Asia
Salzberg SL, et al. EID. 2007. 13(5):713-718.
Salzberg SL, et al. EID. 2007. 13(5):713-718.
H5N1 pathology/disease
Cell tropism: HA, NA
High viral replication: PA, PB1, PB2, NP
Host immune response: NS
HA cleavability determinates the tissue tropismHorimoto T, et al. Nature Reviews of Microbiology. 2005. 3:591-600.
Effect of HA and NA on replication of influenza virus
• Influenza viruses bind to sialic acid present on cell surface through the receptor-binding site in the HA molecules followed by receptor-mediated endocytosis during viral entry (Hanson et al., Virology 1992).
• The NA cleaves the Neu5Ac from the HA molecule to release the progeny virus from the cell membrane and to prevent aggregation of progeny virions (Rogers et al., Virology 1989).
• This NA enzymatic activity, however, also cleaves the receptor from the target cells.
• Therefore, the balance between the receptor-binding activity of the HA and the neuraminidase activity of the NA is critical for efficient virus replication in host cells (Kaverin et al., Virology 1998).
The NA stalk was correlated with the efficiency of virus replication
Castrucci MR, et al. Journal of Virology. 1993. 67:759-764.
NA Stalk
poly-A binding protein II (PABII) binding domain (223-237)