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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

D. A. Senne, B. Panigrahy, Y. Kawaoka, J. E. Pearson, J. Süss, M. Lipkind, H. Kida and R. G. Webster
Avian Diseases
Vol. 40, No. 2 (Apr. - Jun., 1996), pp. 425-437
DOI: 10.2307/1592241
Stable URL: http://www.jstor.org/stable/1592241
Page Count: 13
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Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.
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
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Abstract

The deduced amino acid sequence at the hemagglutinin (HA) cleavage site of 76 avian influenza (AI) viruses, subtypes H5 and H7, was determined by reverse transcription-polymerase chain reaction and cycle sequencing techniques to assess pathogenicity. Eighteen of the 76 viruses were isolated in 1993 and 1994 from various sources in the United States. In addition, 34 H5 (4 highly pathogenic [HP] and 30 non-highly pathogenic [non-HP]) and 24 H7 (3 HP and 21 non-HP) repository viruses, isolated between 1927 and 1992, were sequenced and the sequences compared to those in recent isolates. All repository HP H5 and H7 viruses studied had multiple basic amino acids adjacent to the HA cleavage site and most had basic amino acids in excess of the proposed minimum motif B-X-B-R (B = basic amino acids arginine or lysine, X = nonbasic amino acid, R = arginine) that has been associated with high pathogenicity. Of the non-HP viruses studied, 35 of 38 for H5 and 30 of 31 for H7 conformed to the motif B-X-X-R and B-X-R, respectively. Two non-HP H5 viruses had the motif X-X-X-R at the cleavage site and a third had the motif B-X-X-K (K = basic amino acid lysine). One non-HP H7 (A/Pekin robin/CA/30412-5/94) had four basic amino acids (K-R-R-R) adjacent to the cleavage site. Although the Pekin robin isolate did not produce disease in chickens under the conditions of the study it did have the amino acid sequence compatible with that in HP AI viruses and, therefore, is considered potentially HP. This is the first account of an H7 virus that is non-HP in chickens but meets the molecular criterion to be classified as HP. /// Por medio de la reacción en cadena por la polimerasa y transcripción reversa, lo mismo que por técnicas secuenciadoras de ciclo, se determinó la secuencia de aminoácidos del sitio de corte de la hemoaglutinina. Se examinaron 76 cepas del virus de influenza pertenecientes a los subtipos H5 y H7, 18 de ellas fueron aisladas en los Estados Unidos entre 1993 y 1994 a partir de varios casos. Además, del depositario de virus de influenza se estudiaron virus aislados entre 1927 y 1992, comparando sus secuencias con las de las cepas aisladas más recientemente. Estos virus fueron 34 cepas H5 (4 altamente patógenas y 30 no altamente patógenas) y 24 cepas H7 (3 altamente patógenas y 21 no altamente patógenas). Todas las cepas H5 y H7 altamente patógenas del depositario tuvieron múltiples aminoácidos básicos adyacentes al sitio de corte de la hemoaglutinina y la mayoría tenían aminoácidos básicos en exceso del esquema mínimo propuesto para las cepas altamente patógenas: B-X-B-R (B = aminoácido básico -arginina o lisina-; X = aminoácido no básico, R = arginina). De las cepas no altamente patógenas estudiadas, 35 de las 38 cepas H5 y 30 de las 31 cepas H7 correspondieron al esquema B-X-X-R y B-X-R, respectivamente. Dos cepas H5 no altamente patógenas tuvieron el esquema X-X-X-R en el sitio de corte y una tercera tenía el esquema B-X-X-K (K = aminoácido básico lisina). La cepa no altamente patógena H7 (A/Pekin robin/CA/30412-5/94) tenía 4 aminoácidos (K-R-R-R) adyacentes al sitio de corte. Aunque bajo las condiciones del estudio esta cepa no produjo enfermedad en pollos, tuvo una secuencia de aminoácidos compatible con los virus de influenza de alta patogenicidad y por lo tanto es considerada potencialmente como de alta patogenicidad. Este es el primer reporte de un virus tipo H7 que no es patógeno en pollos pero que reune el criterio molecular para ser clasificado como de alta patogenicidad.

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