0:04 influenza infection it might start with
0:06 a sneeze but the underlying infection
0:08 can cause far worse hundreds of
0:10 thousands of people every year die from
0:16 infection everything begins when the
0:30 Airways here influenza viruses specific
0:31 ly attached to the surface of the epithelial
0:32 epithelial
0:35 cells the viral membrane envelope
0:38 contains the neurom medad protein na
0:39 important for the efficient release of
0:42 newly produced viruses the M2 ION
0:44 channel promotes viral structural
0:47 changes during cellular entry and the
0:50 influenza hemog glutenin protein ha the
0:52 key player for viral internalization
0:55 which facilitates viral binding to cic
0:57 acid decorated receptors and
1:00 subsequently viral Fusion
1:02 proteolytic cleavage by host enzymes is
1:12 primers soluble or cell-bound host
1:14 proteases cleave the precursor ha
1:27 ha2 influenza virus particles are
1:29 internalized into early endosomes by
1:32 Cline mediated [Music]
1:38 [Music]
1:40 endocytosis in late endosomes the pH
1:42 drops triggering the confirmational
1:46 change of the cleaved ha molecules ha1
1:49 opens up and allows ha2 to form a triple
1:51 Alpha Helix bundle which extends towards
1:53 the endosomal [Music]
1:54 [Music]
1:57 membrane once the fusion pepines are
1:59 Anchored In The endosomal Membrane the
2:02 full molecule can fold back allowing the
2:05 fusion of the viral and endosomal
2:08 membranes after Fusion the viral genome
2:10 can be released into the cytool the
2:12 eight viral RNA segments make their way
2:14 into the cell nucleus and the production
2:17 of the new virus begins just hours after
2:19 the initial infection thousands of new
2:21 viruses butt off the cell surface and
2:28 cells to stop the influence infection
2:30 crusell researchers have discovered
2:32 fully human monoclonal antibodies
2:34 capable of neutralizing the [Music]
2:44 virus these antibodies specifically bind
2:46 to the ha and are internalized together
2:52 virus when the pH drops in late
2:54 endosomes the antibodies remain bound to
2:57 a highly conserved epitope located in
3:01 the stem of the ha
3:02 the antibodies now block the
3:05 confirmational change of ha thereby
3:14 infection the trapped virus degrades
3:16 leaving the cell [Music]
3:25 [Music]
3:28 unharmed some of cruel's new antibodies
3:32 can also prevent the initial cleage of
3:34 ha they bind to a highly conserved
3:37 epitope close to the ha cleavage site
3:39 thereby preventing host protasis from
3:47 virus the uncleaved virus is not
3:59 safe cruells neutralizing anybody's
4:01 prevent the spread of influenza
4:08 [Music] [Applause]
