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OIE/FAO
Network of expertise on animal influenza

OIE - World Organization for Animal HealthFAO - Food and Agriculture Organization of the United Nations
Reported heamagglutinin proteolytic cleavage site of HA0 protein for H5 and H7 LPAI and HPAI viruses based on deduced amino acid sequence (adapted from refs 8 and 10)
Amino acid sequence Outbreak Pathotype References
H5 avian influenza viruses1      
PQ......RETR*GLF Typical H5 LPAI LP (10)
PQ........RKKR*GLF Scotland/1959, Texas-USA/2004 HP (6)
PQ....RRRKKR*GLF Ontario-Canada/1966, Italy/1997 HP (6)
PQ....RKRKKR*GLF Ireland/1983 HP (6)
PQREKRRKKR*GLF South Africa/2006, 2006; H5N1 Eurasian-African lineage (1996-) HP (1)
PQRERRRKKR*GLF H5N1 Eurasian-African lineage (1996-) HP (8)
PQREIRRKKR*GLF HP    
PQIERRRKKR*GLF HP    
PQGERRRKKR*GLF HP    
PLRERRR..KR*GLF HP    
PRIERRRKKR*GLF HP    
PQRERIRKKR*GLF HP    
PQRE.RRKKR*GLF HP    
PQKERRRKKR*GLF HP    
PQRERKRKKR*GLF HP    
PQRESRRKKR*GLF HP    
PQRE..KRKKR*GLF HP    
PLRE..RRKKR*GLF HP    
PQGDRRRKKR*GLF HP    
PQGEGRRKKR*GLF HP    
PQ....RKRKTR*GLF England/1991 HP (10)
PQ....RKRKTR*GLF
PQRKRKRKTR*GLF
Mexico/1994-95 HP (4, 5)
PQRETRRQKR*GLF South Africa/1961 HP (10)
PQ........KKKR*GLF2 Pennsylvania-USA/1983 HP (10)

     
H7 avian influenza viruses      
PEIP...........................KTR*GLF
PEIP...........................KGR*GLF
PEKP..........................KTR*GLF
PENP..........................KTR*GLF
Typical H7 LPAI LP (10)
PEIP...................KKREKR*GLF England/1963, Victoria-Australia/1975, Victoria-Australia/1985 HP (10)
PEIP................KKRKR*GLF England/1979 HP (1, 14)
PEIP................RKRKR*GLF Queensland-Australia/1994, New South Wales-Australia/1997 HP (11)
PETP.............KRKRKR*GLF
PETP...............KRRKR*GLF
PETP...............KRRNR*GLF
Pakistan/1995 HP (2)
Temporary addition to Chapter 2.3.4. – Avian influenza
Amino acid sequence Outbreak Pathotype References
PETP....................KRRRR*GLF England/1963 HP (14)
PEIP................KRRRR*GLF England/1979, Netherlands/2003   (1, 14)
PEIP...............KKKKR*GLF
PEIP.............  KRKKR*GLF
PEIP......... ...KKRKKR*GLF
PEIP......  ...KKKKKKR*GLF
Leipzig-Germany/1979, VictoryAustralia/1992 HP (9)
PEIPKG................SRVRR*GLF
PEIPKG.............SRMRR*GLF
PEIPKR.................SRVRR*GLF
Italy/1999 HP (3)
PEKPKTCSPLSRCRETR*GLF
PEKPKTCSPLSRCRKTR*GLF
Chile/2002 HP (12)
PENPK.....QAYRKRMTR*GLF
PENPK.....QAYQKRMTR*GLF
PENPK.....QAYKKRMTR*GLF
PENPK.....QAYHKRMTR*GLF
PENPK.....QAHQKRMTR*GLF
PENPR.....QAYRKRMTR*GLF
PENPK.....QACQKRMTR*GLF
British Columbia-Canada/2004 HP (7)
PEIPK.........GRHRRPKR*GLF North Korea/2005 HP (13)

1. = site of HA0 cleavage into HA1 and HA2, underlined amino acids are inserts

2. High pathogenicity phenotype also required loss of the shielding glycosylation site at residue 13

References

  1. ALEXANDER D.J., CAPUA I. & KOCH G. (2008). Highly pathogenic avian influenza outbreaks in Europe, Africa and Asia since 1959, excluding the Asian H5N1 virus outbreaks.  In: Avian Influenza, Swayne D.E., ed. Blackwell Publishing, Ames, Iowa, USA, pp. 217–237. 
  2. BANKS  J., SPEIDEL  E.C., MCCAULEY  J.W. & ALEXANDER  D.J. (2000). Phylogenetic analysis of H7 haemagglutinin subtype influenza A viruses. Arch. Virol., 145, 1047–1058. 
  3. CAPUA I., MUTINELLI F., MARANGON S. & ALEXANDER D.J. ( 2000). H7N1 avian influenza in Italy (1999 to 2000) in intensively reared chickens and turkeys. Avian Pathol., 29, 537–543. 
  4. GARCIA M., CRAWFORD J.M., LATIMER J.W., RIVERA-CRUZ M.V.Z.E. & PERDUE M.L. (1996). Heterogeneity in the hemagglutinin gene and emergence of the highly pathogenic phenotype among recent H5N2 avian influenza viruses from Mexico. J. Gen. Virol., 77, 1493–1504. 
  5. HORIMOTO T., RIVERA E., PEARSON J., SENNE D., KRAUSS S., KAWAOKA Y. & WEBSTER R.G. (1995). Origin and molecular changes associated with emergence of a highly pathogenic H5N2 influenza virus in Mexico. Virology, 213, 223–230. 
  6. LEE  C.W., SWAYNE  D.E., LINARES  J.A., SENNE  D.A. & SUAREZ  D.L. (2005). H5N2 avian influenza outbreak in Texas in 2004: the first highly pathogenic strain in the United States in 20 years? J. Virol., 79, 3692–3702. 
  7. PASICK J., HANDEL K., ROBINSON J., COPPS J., RIDD D., HILLS K., KEHLER H., COTTAM-BIRT C., NEUFELD J., BERHANE Y. & CZUB S. (2005). Intersegmental recombination between the haemagglutinin and matrix genes was responsible for the emergence of a highly pathogenic H7N3 avian influenza virus in British Columbia. J. Gen. Virol., 86, 727–731. 
  8. PERDUE M.L. (2008). Molecular determinants of pathogenicity for avian influenza viruses. In: Avian Influenza, Swayne D.E., ed. Blackwell Publishing, Ames, Iowa, USA, pp. 23–41. 
  9. ROHM C., SUSS J., POHLE V. & WEBSTER R.G. (1996). Different hemagglutinin cleavage site variants of H7N7 in an influenza outbreak in chickens in Leipzig, Germany. Virology, 218, 253–257. 2 OIE Terrestrial Manual 2009 Temporary addition to Chapter 2.3.4. – Avian influenza 
  10. SENNE D.A., PANIGRAHY B., KAWAOKA Y., PEARSON J.E., SUSS J., LIPKIND M., KIDA H. & WEBSTER R.G. (1996). Survey of the hemagglutinin (HA) cleavage site sequence of H5 and H7 avian influenza viruses: amino acid sequence at the HA cleavage site as a marker of pathogenicity potential. Avian Dis., 40, 425–437. 
  11. SIMS L.D. & TURNER  A.J. (2008). Avian influenza in Australia. In: Avian Influenza, Swayne D.E., ed. WylieBlackwell Publishing, Ames,Iowa, USA, pp. (in press).  
  12. SUAREZ D.L., SENNE D.A., BANKS J., BROWN I.H., ESSEN S.C., LEE C.W., MANVELL R.J., MATHIEU-BENSON C.,MORENO V., PEDERSEN J.C., PANIGRAHY B., ROJAS H., SPACKMAN E. & ALEXANDER D.J. (2004). Recombination resulting in virulence shift in avian influenza outbreak, Chile. Emerg. Infect. Dis., 10, 693–699. 
  13. SWAYNE D.E. (2008). The global nature of avian influenza. In: Avian Influenza, Swayne D.E., ed. Blackwell Publishers, Ames, Iowa, USA, pp. 123–143. 
  14. WOOD G.W., MCCAULEY J.W., BASHIRUDDIN J.B. & ALEXANDER D.J. (1993). Deduced amino acid sequences at the haemagglutinin cleavage site of avian influenza A viruses of H5 and H7 subtypes. Arch. Virol., 130, 209–217.

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