Influenza 101

http://mbio.asm.org/content/1/1/e00018-10.full?sid=36775023-0a6d-42e8-b971-eae3db2a9b9d

This is a pretty cool article that came out the other day about making universal influenza vaccines by taking the head off of HA and using the stalk as an immunogen (in mice). Considering how rapidly influenza can evolve, could strains with different stalks emerge which escape the vaccine--or would that make the HA non-functional? Why does the immune system normally produce antibodies to the HA globular head rather than the stalk?

Why are most of the clinical articles recommending use of oseltamivir when it has greater capacity to cause resistance than zanamivir? Is it because zanamivir is inhaled vs. oseltamivir pill?

Yes, inhalation is not as widely accepted as an ingested pill. It's
probably driven by physician preferences. If the docs said 'do you
want an inhaled formulation that is less likely to lead to
resistance', I think many people would say yes, but the choice is
rarely offered - tamiflu seems to be the default.

hellow sir i want to know clearly about hemagglutunin. I'm a student of biotechnology i'm taking seminar about H1N1 influenza i said to my frnds dat HA have trimester structure so dat wen it enters into host cell it binds to sialic acid as it have a trimester structure. But my sir said its wrong,it only binds to cabohydrate residue so dat it gets bound to sialis acid , can u plz suggest me about dis structure clearly

The influenza HA is a trimer on the virion surface. It binds to sialic
acids on the cell surface which are the receptor for the virus. This
binding leads to uptake of virions by receptor-mediated endocytosis.
You can find more information at
http://www.virology.ws/2009/05/04/influenza-virus-attachment-to-cells/.

Regarding H1N1 and its apparent massive inflamatory response in the airways. This would increase the alveolar capillary membrane thickness. Add this to the epithelial cell ulceration occuring . Its seems that this is the cause of the severe hypoxemia seen clinically. My question is are we treating the underlying cause of hypoxemia? I feel that these patients should be hit with high dose antihistamines and an inhaled steroids such as pulmicort as frequently as possible before it's top late. This may get the patient thru the massive inflammatory response which seems to be the culprit to so many deaths in H1N1. Maybe it will buy the patients enough time to tackle the virus which is supposed to be self-limited in nature anyways if the hypoxemia did not get in the way so much. What do you think?

We have very little 2009 H1N1 flu at this time, but what puzzles me is that there is NO seasonal influenza !!! What do you think has happened- cross immunity- high herd immunity? ....????

There are a number of theories; one is 'original antigenic sin', the
idea that infection with contemporary strains preferentially induces
antibodies to older strains that the host has been exposed to. We
discussed this in TWiV #16: check out this link for some references
http://www.twiv.tv/2009/12/06/twiv-61-original-antigenic-sin/

Respected Professor VRR,
I am chandra sekhar with computer science background,Recently i started my research in bioinformatics, I am very much interested to work with influenza related data,
Could you please suggest me any research problem to work with influenza data .


Thanks in advance

Marvellous, fabulus, splendid...........................explanation. very simple and scientific blog.

ur explanations r simple n very informative. :D

In my area (Italy) the incidence of A(H1N1)v influenza is rapidly decreasing. Cases have reached their peak during week 45, according to the sentinel surveillance of ILIs:
http://www.iss.it/binary/iflu/cont/Italia2009_50.pdf
At present, pediatricians point out that respiratory infections due to "minor" viruses (like common cold and others) seem to be absent. Waiting rooms are empty: respiratory infections that usually affect children during the winter apparently have disappeared . How can we explain this finding? Thank you

Clearly it cannot be explained by the presence of influenza because,
as the graph in that document shows, the number of infections are low
(although not zero). I would be careful in trying to interpret what
pediatricians point out, as this information could be erroneous.

Regarding egg-based vaccine production: could you explain how virus replicates in chicken eggs? Does replication occur in the embryo and if so, how does it end up so concentrated in the egg white? Thanks!

Regarding egg-based vaccine production: could you explain how virus replicates in chicken eggs? Does replication occur in the embryo and if so, how does it end up so concentrated in the egg white? Thanks!

The virus is inoculated into the allantoic cavity of embryonated
chicken eggs (10-12 day old embryos). The virus multiplies in the
cells of the allantoic membrane which surround the allantoic fluid. As
these cells produce virus it is shed into the allantoic fluid. I'll
put up a post on this with an illustration to make it clear.

I forgot: I noticed that you do not discuss the vitamin D influenza hypothesis in your seasonality and innate imunity topics. What is your take on the hypothesis?

Ref.
Epidemiol Infect. 2006 Dec;134(6):1129-40.
Epidemic influenza and vitamin D.
Cannell JJ, Vieth R, Umhau JC, Holick MF, Grant WB, Madronich S, Garland CF, Giovannucci E.

Some notes on vaccines/vaccination and pros/cons of different modes of application and "adjuvants" would also be very appreciated.

I would like to konw if the new novel flu H1N1 is a cause of a shift or drift?

By definition it is antigenic drift, because the subtype - H1N1 - is the same as the previous seasonal H1N1 viruses. It's different from what we have seen before, because the HA differs by many more amino acids than one would expect to occur from one season to another. However, there are certainly drifted strains of the same subtype many years apart that differ by that much. So It's drift, albeit an unusual form.

Vincent - I've been thinking about this shift/drift factoid all summer. In the end, I guess the distinction is purely academic but I think 2009/H1N1 is in fact an example of antigenic shift.

Before April, most epidemiologist/virologist/public health types would mostly agree that shift is indicated by a newly circulating HA or at the very least NA. So by this example, shift would not fit; however, everyone would agree the 2009/H1N1 is a result of a reassortment and I have not found one single reference that places words 'reassortment' and 'drift' in the same sentence - reassortment is always associated with shift!

Therefore I'm going with shift..there I feel better now (please don't flame me to bad on this one). BTW, love the new virology 101 section!!!

I don't think pandemic swine H1N1 can be called a drift variant, unless you are calling it a drift variant of swine H1N1 that has gained efficient transmissibility in humans. Although human H1N1 and swine H1N1 share the same serotype, the sequences are quite distinct and have been distinct since the first viruses were isolated in the 1930's. The first influenza isolate was H1N1 from a pig in Iowa in 1930, and the first human isolate was from a researcher in England in 1933. The two lineages were easily distinguished, and these seperate lineages have been maintained ever since (and probably also maintained well before the 1930's).

Antigenic shift is reserved for reassortment where one of more gene segments jumps from one lineage to another and frequently involves different serotypes.

The current swine is called a triple reassortant because it has one gene segment (PB1) from human flu, and two (PB2 and PA) from avian flu, but the H1 and N1 are swine and are not caused by any recent drifting, severe or mild. Swine H1N1 and human H1N1 are completly different lineages.

The 2009 H1N1 strain in some ways defies our definitions of drift and
shift. Here are the textbook definitions. Antigenic drift: the
appearance of virions with slightly altered surface proteins following
passage in the natural host. Antigenic shift: a major change in the
surface protein(s) of a virion as genes encoding completely new
surface proteins are acquired. This dramatic change in virion
composition results when a host is coinfected with two viral
serotypes. The 2009 swine-derived H1N1 does not fit either definition.
Antigenic shift, as you note, has typically involved a change in
subtype: 1889 H2N2; 1900 H3N8; 1918 H1N1; 1957 H2N2; 1968 H3N2; 1977
H1N1; 2009 H1N1. But perhaps a change in subtype should not be part of
the definition of shift. As you point out, the 2009 H1N1 is very
different from the human H1N1 and that is probably sufficient to make
it shift. What confounds the problem is that as different as the swine
and human H1 are, they are still H1 subtypes.

After years of tamiflu treatment, seasonal flu became mild resistent strain.
But with h1n1 new virus, after only 2 month of experience, just has appeared in denmark and japan the new H274Y mutation on treated patients. It seems to be a swift ,smart (and chilling) virus. what's next?

This is a great resource -- especially for a journalist like me who is based in India.

Hello,
It would be good to hear your thoughts on A/Shanghai/71T/2009 that has just appeared with both the PB2 E627K and D701N mutations. It took 43 days to adapt! D701N is thought to allow E627 viruses to become infectious to humans and perhaps has led to the E627K arising. Both are quite scary individually and together I think they look very worrying - transmissibility should be increased due to more efficient replication in the cooler temperatures of the respiratory tract.

Looks like a red herring. The sequence has recently been corrected and updated in the database -- see GenBank GQ253501.2 GI:241914528. Neither the E627K nor the D701N mutations are present.

Vincent, this is fantasic. Could you also add a section on the human immune response? I think understanding the human side is just as important as understanding the viral side.

I'll be adding sections on the immune response to influenza infection
in the next week or two.