Comments on: Influenza HA cleavage is required for infectivity

By: David

David — Sun, 08 Aug 2010 14:55:26 +0000

Thats interesting and thanks for the information you are providing. pls bear with me for the question. As the HA pass through TGN, is it possible that it can bind to the host proteins bearing sialic acid? if so, Then NA should work from TGN. Is there any report showing that inhibition of NA can accumulate HA in TGN? any known host protein interacting with HA in TGN and retain HA for short period of time? untill, NA cleaves it to release HA to go plasma membrane.

By: profvrr

profvrr — Thu, 26 Nov 2009 00:32:16 +0000

There are amino acid changes in the influenza HA that are known to
allow cleavage by cellular proteases that are in many tissues, ie not
restricted to the respiratory tract. But no 2009 H1N1 isolate has
these mutations. As far as I know this strain is not neurotropic.

By: profvrr

profvrr — Wed, 25 Nov 2009 16:32:16 +0000

By: kate felmet

kate felmet — Mon, 23 Nov 2009 23:07:57 +0000

Thank you for this information. Have you seen any reports of a mutation that would change the type of protease capable of cleaing the 2009 H1N1? I'm asking because of the number of cases of encephalitis/encephalopathy we're seeing n children from a virus that one wouldn't expect to be neurotropic. we haven't recovered virus form the CNS, but the clinical syndrome is unusual. SInce it has occurred in almost 3% of hospitalized children in my area, I thought it might be worth looking into what mutations may have been described.

By: profvrr

profvrr — Tue, 22 Sep 2009 19:26:10 +0000

HAs with a multibasic cleavage site (some H5 and H7 subtypes) are
cleaved into HA1 and HA2 by furins in the trans-Golgi network.

By: audreylarrimer

audreylarrimer — Tue, 22 Sep 2009 17:06:35 +0000

Is the HA always cleaved extracellularly? Is it ever cleaved during protien modification in the golgi?

By: becunnin

becunnin — Tue, 23 Jun 2009 22:18:51 +0000

I am a novice so bear with me. I wondered if because the absence of A1At allows elastase to break down elastin in the lung and because elastase is said to break down cytokines-is it possible then that alpha one anti-trypsin deficient individuals would be protected from the possibility of a cytokine storm?

The effect of influenza of course would lead to lung damage from the lack of protection A1AT offers-but would the lack of it offer protection from something more severe such as a cytokine storm?

By: profvrr

profvrr — Tue, 23 Jun 2009 20:07:26 +0000

Great question. The problem is that we don't know which specific
protease is responsible for HA cleavage in the respiratory tract. We
do know that trypsin, plasmin, factor X-like protease, tryptase Clara,
and miniplasmin do cleave influenza HA. Tryptase Clara is secreted
from the respiratory epithelium of rats and mice, while miniplasmin is
found in bronchial epithelial cells. Tryptase Clara is not inhibited
by alpha-1 antitrypsin. I have never seen a report that suggests more
susceptibility to influenza, or more serious disease, in people with
alpha-1 antitrypsin deficiency.

By: becunnin

becunnin — Tue, 23 Jun 2009 19:43:45 +0000

Due to the role of trypsin for infectivity, what role would alpha one antitrypisn deficiency play in those who become infected with influenza-particularly this H1N1 strain? Also-would the alpha one antityrpsin deficiency make it more likely for someone to become infected with influenza and/or this strain of influenza?