Update on Influenza Virus Surveillance Findings in 2008/09 Season in Northern Hemisphere Who Collaborating Center for Reference and Research on Influenza at Center for Influenza Virus Research, National Institute of Infectious Diseases, Tokyo, Japan Takato Odagiri, Ph.D.

Weekly report of virus isolation/detection in season By NIID By CDC Pandemic A/H1N1 viruses

A(H1N1) viruses September 2008-January 2009

H1N1, Sept 2008 – Jan 2009

H1N1 antigenic analysis By NIID

H1N1 antigenic analysis By CDC

Summary of antigenic analysis of A/H1N1 in four WHO CCs A/Br/59/07-like low-reactors (≥ 8-f) CDC (Oct-) 179 [100%] 0 [0%] NIID (Oct-) 72 [95%] 4 [5%] NIMR (Oct-) 62 [87%] 9 [13%] VIDRL (Oct-) 119 [97.5%] 3 [2.5%] Total 432 [96%] 16 [4%]

March-July 2009

By CDC

By NIMR

Antigenic characterization of AH1N1 viruses isolated after March By NIID By CDC

Number of oseltamivir resistance viruses isolated in Japan （ Oct 2008-May 2009 ） By NIID

H1N1 viruses - Summary Oct 2008-Feb 2009 Influenza A(H1N1) viruses predominated in many Asian and North American countries The majority of viruses were antigenically closely related to A/Brisbane/59/2007 by HI analysis Phylogenetically the majority of H1N1 viruses grouped into the A/Brisbane/59/2007 clade (2B) based on their HA gene. Recent 2B viruses share H275Y indicative of resistance to oseltamivir. They were antigenically similar to osel-sensitive viruses. Recent viruses from China fall within the A/Hong Kong/2652/2006 clade (2C) and these viruses were similar antigenically to clade 2B viruses. Clade 2C viruses are sensitive to oseltamivir and resistant to amantadine/rimantadine Mar - July 2009 The features of viruses were similar to those observed earlier in Majority of recent A(H1N1) viruses were antigenically closely related to A/Brisbane/59/2007 and formed clade 2B sharing H275Y. In the few clade 2C viruses, dual resistance to oseltamivir and amantadine/rimantadine were detected.

A(H3N2) viruses September 2008-January 2009

H3N2, Sept 2008 – Jan 2009

By NIID

By NIMR

A/Brisbane/10/07-like low-reactors (≥ 8-f) CDC (Oct-) 45 [90%] 5 [10%] NIID (Oct-) 32 [56%]25 [44%] NIMR (Oct-)160 [90%]18 [10%]* VIDRL (Oct-)145 [93%]11 [ 7%] Total382 [87%]59 [13%] H3 low reactors in HI assays in WHOCCs * 0% by virus neutralization

Vaccine virus

March-July 2009

By NIMR

By NIID

Vaccine virus

By Cambridge Univ.

H3N2 viruses - Summary Oct 2008-Feb 2009 H3N2 viruses co-circulated with H1N1 and B viruses in many countries Majority were antigenically similar to A/Brisbane/10/07 and A/Uruguay/716/07 by HI tests with turkey RBCs or guinea pig RBCs. The ‘low reactors’ were antigenically indistinguishable from vaccine viruses by Neutralization tests. HA and NA sequences fairly homogeneous and fell within the A/Brisbane/10/07 clade M2 sequences possessed S31N mutation, indicative of amantadine resistance Sensitive to oseltamivir and zanamivir Mar - July 2009 Majority were antigenically similar to vaccine viruses. An increasing number of H3N2 isolates have been shown to be antigenically distinct from vaccine viruses and related to A/Hawaii/7/09, A/HK/1985/09 and A/Perth/16/09. The majority of HA sequences of those viruses formed a separate clade characterized by aa subsitutions E62K, N144K, K158N and N18K. They retained resistance to amantadine/rimantadine and were sensitive to oseltamivir and zanamivir.

B viruses September 2008-January 2009

B, Sept 2008 – Jan 2009

Numbers of 2 lineages of B viruses detected in GISN since week B-Victoria lineage B-Yamagata lineage

HI reactions of influenza type B viruses By NIID

HI reactions of influenza type B viruses B/Victoria-lineage By NIMR

HI reactions of influenza type B viruses B/Yamagata lineage By NIMR

Victoria Yamagata CDC (Oct-)71 [60%]48 [40%] low reactors (77%) (23%) NIID (Oct-)18 [40%] 27[60%] Low reactors (94%) (67%) NIMR 17 [44%] 22[56%] Low reactors (76%) (14%) VIDRL (Oct-)340 [67%]167 [33%] Low reactors (94%) (62%) Total446 [63%] 264 [37%] Low reactors (91%) (51%) B low reactors in HI assays in WHOCCs

10 nucleotides B/Brisbane/60/2008-like Evolutionary Relationships Among Influenza B (Victoria Lineage) HA Genes B/Malaysia/2506/2004 K165N Chinese clade By Melbourne C.

Evolutionary Relationships Among Influenza B (Yamagata Lineage) HA Genes 10 nucleotides By Melbourne C.

March-July 2009

By NIMR HI reactions of influenza type B viruses B/Victoria-lineage

By CDC

By Cambridge Univ.

B/Victoria-lineage HA By NIID Vaccine virus Chinese viruses

By CDC B/Yamagata-lineage HA Vaccine virus

Summary for influenza B viruses Oct 2008-Feb 2009 Influenza B viruses circulated in many countries however regional outbreaks were limited. Viruses of both B/Victoria/2/87 and B/Yamagata/16/88 lineages continued to co-circulate in many countries B/Victoria-lineage viruses predominated in most countries and were mostly antigenically closely related to B/Brisbane/60/2008. Viruses mainly from China fell into a separate phylogenetic clade B/Yamagata-lineage viruses were antigenically closely related to B/Florida/4/2006 & B/Brisbane/3/2007 vaccine viruses. Three phylogenetic clades were apparent but were antigenically indistinguishable. Mar - July 2009 B/Victoria-lineage viruses predominated and were mostly antigenically closely related to vaccine strain B/Brisbane/60/2008. Many viruses isolated in China were closely related to B/Fujian Gulou/1272/08 and B/Hubei-Songzi/51/08. B/Yamagata-lineage viruses were antigenically closely related to B/Florida/4/2006 and mostly fell into their HA sequences of the B/Bagladesh/3333/07 clade.

WHO Collaborating Centers ( US-CDC, NIMR, Melbourne ) Cambridge University NICs (China-CDC, Korea-CDC, NHL-Myanmar, NCLE-Lao PDR, NIH-Mongolia and other NICs of WHO GISN) Taiwan-CDC Local PHLs in Japan Acknowledgement