tetano
Editor, Senior Moderator
J Virol. 2013 Jul 17. [Epub ahead of print]
The short stalk length of HPAI H5N1 influenza neuraminidase limits transmission of pandemic H1N1 virus in ferrets.
Blumenkrantz D, Roberts KL, Shelton H, Lycett S, Barclay WS.
Source
Section of Virology, Division of Infectious Disease, Imperial College London, St Mary's Campus, Norfolk Place, London W2 1PG, UK.
Abstract
H5N1 influenza viruses pose a pandemic threat but have not acquired the ability to support sustained transmission between mammals in nature. The restrictions to transmissibility of avian influenza viruses in mammals are multigenic and overcoming them requires adaptations in HA and PB2 genes. Here we propose that a further restriction to mammalian transmission of the majority of HPAI H5N1 viruses may be the short stalk length of the NA protein. This genetic feature is selected for when influenza viruses adapt to chickens. In our study a recombinant virus, with seven gene segments from a human isolate of the 2009 H1N1 pandemic combined with the NA gene from a typical chicken-adapted H5N1 virus with a short stalk, did not support transmission by respiratory droplet between ferrets. This virus was also compromised in multicycle replication in cultures of human airway epithelium at 32?C. These defects correlated with a reduction in the ability of virus with a short stalk NA to penetrate mucus and de-aggregate virions. The deficiency in transmission and in cleavage of tethered substrates was overcome by increasing the stalk length of the NA protein. These observations suggest that H5N1 viruses that acquire a long stalk NA through reassortment might be more likely to support transmission between humans. Phylogenetic analysis showed that reassortment with long stalk NA occurred sporadically and as recently as 2011. However, all identified H5N1 viruses with a long stalk NA lacked other mammalian adapting features and were thus several genetic steps away from becoming transmissible between humans.
PMID:
23864615
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/23864615
The short stalk length of HPAI H5N1 influenza neuraminidase limits transmission of pandemic H1N1 virus in ferrets.
Blumenkrantz D, Roberts KL, Shelton H, Lycett S, Barclay WS.
Source
Section of Virology, Division of Infectious Disease, Imperial College London, St Mary's Campus, Norfolk Place, London W2 1PG, UK.
Abstract
H5N1 influenza viruses pose a pandemic threat but have not acquired the ability to support sustained transmission between mammals in nature. The restrictions to transmissibility of avian influenza viruses in mammals are multigenic and overcoming them requires adaptations in HA and PB2 genes. Here we propose that a further restriction to mammalian transmission of the majority of HPAI H5N1 viruses may be the short stalk length of the NA protein. This genetic feature is selected for when influenza viruses adapt to chickens. In our study a recombinant virus, with seven gene segments from a human isolate of the 2009 H1N1 pandemic combined with the NA gene from a typical chicken-adapted H5N1 virus with a short stalk, did not support transmission by respiratory droplet between ferrets. This virus was also compromised in multicycle replication in cultures of human airway epithelium at 32?C. These defects correlated with a reduction in the ability of virus with a short stalk NA to penetrate mucus and de-aggregate virions. The deficiency in transmission and in cleavage of tethered substrates was overcome by increasing the stalk length of the NA protein. These observations suggest that H5N1 viruses that acquire a long stalk NA through reassortment might be more likely to support transmission between humans. Phylogenetic analysis showed that reassortment with long stalk NA occurred sporadically and as recently as 2011. However, all identified H5N1 viruses with a long stalk NA lacked other mammalian adapting features and were thus several genetic steps away from becoming transmissible between humans.
PMID:
23864615
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/23864615