|
|
|
|
LEADER |
03553 am a22004453u 4500 |
001 |
106676 |
042 |
|
|
|a dc
|
100 |
1 |
0 |
|a Lakdawala, Seema S.
|e author
|
100 |
1 |
0 |
|a Harvard University-
|e contributor
|
100 |
1 |
0 |
|a Massachusetts Institute of Technology. Department of Biological Engineering
|e contributor
|
100 |
1 |
0 |
|a Koch Institute for Integrative Cancer Research at MIT
|e contributor
|
100 |
1 |
0 |
|a Jayaraman, Akila
|e contributor
|
100 |
1 |
0 |
|a Sasisekharan, Ram
|e contributor
|
700 |
1 |
0 |
|a Jayaraman, Akila
|e author
|
700 |
1 |
0 |
|a Halpin, Rebecca A.
|e author
|
700 |
1 |
0 |
|a Lamirande, Elaine W.
|e author
|
700 |
1 |
0 |
|a Shih, Angela R.
|e author
|
700 |
1 |
0 |
|a Stockwell, Timothy B.
|e author
|
700 |
1 |
0 |
|a Lin, Xudong
|e author
|
700 |
1 |
0 |
|a Simenauer, Ari
|e author
|
700 |
1 |
0 |
|a Hanson, Christopher T.
|e author
|
700 |
1 |
0 |
|a Vogel, Leatrice
|e author
|
700 |
1 |
0 |
|a Paskel, Myeisha
|e author
|
700 |
1 |
0 |
|a Minai, Mahnaz
|e author
|
700 |
1 |
0 |
|a Moore, Ian
|e author
|
700 |
1 |
0 |
|a Orandle, Marlene
|e author
|
700 |
1 |
0 |
|a Das, Suman R.
|e author
|
700 |
1 |
0 |
|a Wentworth, David E.
|e author
|
700 |
1 |
0 |
|a Sasisekharan, Ram
|e author
|
700 |
1 |
0 |
|a Subbarao, Kanta
|e author
|
245 |
0 |
0 |
|a The soft palate is an important site of adaptation for transmissible influenza viruses
|
260 |
|
|
|b Nature Publishing Group,
|c 2017-01-30T16:56:08Z.
|
856 |
|
|
|z Get fulltext
|u http://hdl.handle.net/1721.1/106676
|
520 |
|
|
|a Influenza A viruses pose a major public health threat by causing seasonal epidemics and sporadic pandemics. Their epidemiological success relies on airborne transmission from person to person; however, the viral properties governing airborne transmission of influenza A viruses are complex. Influenza A virus infection is mediated via binding of the viral haemagglutinin (HA) to terminally attached α2,3 or α2,6 sialic acids on cell surface glycoproteins. Human influenza A viruses preferentially bind α2,6-linked sialic acids whereas avian influenza A viruses bind α2,3-linked sialic acids on complex glycans on airway epithelial cells. Historically, influenza A viruses with preferential association with α2,3-linked sialic acids have not been transmitted efficiently by the airborne route in ferrets. Here we observe efficient airborne transmission of a 2009 pandemic H1N1 (H1N1pdm) virus (A/California/07/2009) engineered to preferentially bind α2,3-linked sialic acids. Airborne transmission was associated with rapid selection of virus with a change at a single HA site that conferred binding to long-chain α2,6-linked sialic acids, without loss of α2,3-linked sialic acid binding. The transmissible virus emerged in experimentally infected ferrets within 24 hours after infection and was remarkably enriched in the soft palate, where long-chain α2,6-linked sialic acids predominate on the nasopharyngeal surface. Notably, presence of long-chain α2,6-linked sialic acids is conserved in ferret, pig and human soft palate. Using a loss-of-function approach with this one virus, we demonstrate that the ferret soft palate, a tissue not normally sampled in animal models of influenza, rapidly selects for transmissible influenza A viruses with human receptor (α2,6-linked sialic acids) preference.
|
520 |
|
|
|a National Institutes of Health (U.S.)
|
520 |
|
|
|a United States. Dept. of Health and Human Services (Contract HHSN272200900007C)
|
520 |
|
|
|a National Institute of Allergy and Infectious Diseases (U.S.) Genomic Centers for Infectious Diseases (Program U19-AI-110819)
|
546 |
|
|
|a en_US
|
655 |
7 |
|
|a Article
|
773 |
|
|
|t Nature
|