I had to re-write this a bit to understand it; I'm posting it, hoping I got it right.
My summary:
Most HP has serine or threonine at position 346
Lp has valine at 346 and threonine at position 351
We generated virus mutants derived from HPAIV A/Swan/Germany/R65/06 H5N1 (R65) with monobasic cleavage site: R65(mono)-S-ER, and the following additional mutations:
1. R/65 had serine at 346
2. R65-V replaced the serine with valine at position 346
3. R65(mono)-V-ER with serine changed to valine at position 346,
4. R65(mono)-S-ETR and R65(mono)-V-ETR had threonine at position 351.
R65-infected animals (with serine) died within two days.
R65-V (valine) chickens survived longer than R65 infected animals indicating that 346 serine in R65 HA contributes to virulence.
R65(mono)-S-ETR or R65(mono)-S-ER led to slight transient respiratory symptoms
Our data suggest that evolution of H5 HPAIV from low-pathogenic precursors, besides acquisition of a polybasic cleavage site, involves adaptation of neighbouring regions.
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Abstract
The prime virulence determinant of highly pathogenic avian influenza viruses (HPAIV) is the polybasic hemagglutinin (HA) cleavage site. However, engineering of a polybasic cleavage site into an avian influenza virus of low pathogenicity does not result in transformation into HPAIV indicating the importance of other adaptations. Here, we studied the influence on virulence of amino acids adjacent to the HA cleavage site. Most HPAIV of subtype H5 carry serine or threonine at position 346 (corresponding position 323 according to H3-numbering), whereas almost all low pathogenic H5 viruses specify valine. Moreover, all H5 low pathogenic strains carry threonine at position 351 (corresponding position 328 according to H3-numbering)suggesting that acquisition of a polybasic cleavage site involves several steps. We generated virus mutants derived from HPAIV A/Swan/Germany/R65/06 H5N1 (R65) with monobasic cleavage site: R65(mono)-S-ER, and the following additional mutations: R65(mono)-V-ER with serine changed to valine at position 346, and R65(mono)-S-ETR and R65(mono)-V-ETR with threonine inserted at position 351. Moreover, we replaced in the R65 HA serine with valine at position 346 (R65-V). Infection of chickens with R65(mono)-S-ETR or R65(mono)-S-ER led to slight transient respiratory symptoms, whereas R65-infected animals died within two days. However, chickens infected with R65-V survived longer than R65 infected animals indicating that 346 serine in R65 HA contributes to virulence. Our data suggest that evolution of H5 HPAIV from low-pathogenic precursors, besides acquisition of a polybasic cleavage site, involves adaptation of neighbouring regions.
Gohrbandt S, Veits J, Hundt J, Bogs J, Breithaupt A, Teifke JP, Weber S, Mettenleiter TC, Stech J.
Friedrich-Loeffler-Institute, Island of Riems, Germany.
http://www.ncbi.nlm.nih.gov/pubmed/20881092
My summary:
Most HP has serine or threonine at position 346
Lp has valine at 346 and threonine at position 351
We generated virus mutants derived from HPAIV A/Swan/Germany/R65/06 H5N1 (R65) with monobasic cleavage site: R65(mono)-S-ER, and the following additional mutations:
1. R/65 had serine at 346
2. R65-V replaced the serine with valine at position 346
3. R65(mono)-V-ER with serine changed to valine at position 346,
4. R65(mono)-S-ETR and R65(mono)-V-ETR had threonine at position 351.
R65-infected animals (with serine) died within two days.
R65-V (valine) chickens survived longer than R65 infected animals indicating that 346 serine in R65 HA contributes to virulence.
R65(mono)-S-ETR or R65(mono)-S-ER led to slight transient respiratory symptoms
Our data suggest that evolution of H5 HPAIV from low-pathogenic precursors, besides acquisition of a polybasic cleavage site, involves adaptation of neighbouring regions.
-----------------------------------------------------------------
Abstract
The prime virulence determinant of highly pathogenic avian influenza viruses (HPAIV) is the polybasic hemagglutinin (HA) cleavage site. However, engineering of a polybasic cleavage site into an avian influenza virus of low pathogenicity does not result in transformation into HPAIV indicating the importance of other adaptations. Here, we studied the influence on virulence of amino acids adjacent to the HA cleavage site. Most HPAIV of subtype H5 carry serine or threonine at position 346 (corresponding position 323 according to H3-numbering), whereas almost all low pathogenic H5 viruses specify valine. Moreover, all H5 low pathogenic strains carry threonine at position 351 (corresponding position 328 according to H3-numbering)suggesting that acquisition of a polybasic cleavage site involves several steps. We generated virus mutants derived from HPAIV A/Swan/Germany/R65/06 H5N1 (R65) with monobasic cleavage site: R65(mono)-S-ER, and the following additional mutations: R65(mono)-V-ER with serine changed to valine at position 346, and R65(mono)-S-ETR and R65(mono)-V-ETR with threonine inserted at position 351. Moreover, we replaced in the R65 HA serine with valine at position 346 (R65-V). Infection of chickens with R65(mono)-S-ETR or R65(mono)-S-ER led to slight transient respiratory symptoms, whereas R65-infected animals died within two days. However, chickens infected with R65-V survived longer than R65 infected animals indicating that 346 serine in R65 HA contributes to virulence. Our data suggest that evolution of H5 HPAIV from low-pathogenic precursors, besides acquisition of a polybasic cleavage site, involves adaptation of neighbouring regions.
Gohrbandt S, Veits J, Hundt J, Bogs J, Breithaupt A, Teifke JP, Weber S, Mettenleiter TC, Stech J.
Friedrich-Loeffler-Institute, Island of Riems, Germany.
http://www.ncbi.nlm.nih.gov/pubmed/20881092