Readers of virology blog have no doubt seen news reports that a Brazilian influenza isolate called A/Sao Paulo/1454/2009 (H1N1) is novel strain with mutations that enable it to infect new hosts. Here is one example of such a report, from The Australian:
Brazilian scientists have identified a new strain of the H1N1 virus after examining samples from a patient in Sao Paulo, a research institute says. The variant has been called A/Sao Paulo/1454/H1N1 by the Adolfo Lutz Bacteriological Institute, which compared it with samples of the A(H1N1) swine flu from California. The genetic sequence of the new sub-type of the H1N1 virus was isolated by a virology team led by one of its researchers, Terezinha Maria de Paiva. The mutation was comprised of alterations in the Hemagglutinin protein which allows the virus to infect new hosts, it said.
There is nothing novel about this Brazilian isolate. Comparison of the amino acid sequence of the HA protein of A/Sao Paulo/1454/H1N1 with those of other isolates of the current pandemic strain reveals no alterations in the HA protein which would allow the virus to infect new hosts. The HA protein of this virus and many other 2009 H1N1 isolates are identical. The few amino acid differences with other 2009 H1N1 isolates are in areas that would not be expected to influence antigenicity or host range.
I’ll give the journalists the benefit of doubt: perhaps they misinterpreted the statements of the Brazilian scientist. But they should have confirmed their story with a virologist. They would have learned within a few minutes that there is nothing novel about A/Sao Paulo/1454/2009 (H1N1).
I already Twittered the HA aa differences between the California/04/2009 and the San Paulo/1454/2009. Two changes that could lead to some variation P100S and T214A but nothing that should create any kind of panic.
In addition, the identity of the San Paulo strain with some other
early isolates (e.g. Texas) also indicates that there is nothing to
worry about.
Pingback: Brazilian influenza H1N1 isolate is not novel | Swine Flu Outbreak
Dr. Racaniello,
Thank you for your excellent blog, which I just found and have started following. I had heard that the swine flu virus so far has not changed form, but a recent death in San Diego county gave me pause:
http://www3.signonsandiego.com/stories/2009/jun…
Especially worrying to me was the following:
” She started having respiratory problems Sunday…The patient died in the emergency room without being hospitalized…the victim was apparently healthy before this illness and had not traveled outside the region.”
Of course the news story is a bit ambiguous here, as the woman's symptoms could have started several days before and only on Sunday did she develop severe respiratory problems…but the speed of the deterioration seems striking here, as well as the fact that she was previously healthy. Could this mean that the virus is becoming more aggressive? Of course we already know that about half the Mexican deaths due to swine flu were in previously healthy young people.
I guess my question is, people have been saying that the virus is generally mild, and certainly most people seem to recover from it. But do we know anything about why some healthy young people recover from swine flu while others are ravaged and killed?
I think we need to know whether the death (or any of the deaths) was due to cytokine storm. If so, then we have reason for concern. If there is a greater opportunity for secondary infection, this too will need investigation. But until we have also the clinical information, we're very much in the dark.
I'm pretty sure that at least some of the deaths in healthy people have been due to a cytokine storm. I've heard in several reports that the cause of death was multiple organ failure and at least one victim was vomiting up blood before he died. But that in itself doesn't tell us whether the virus is becoming more virulent. Remember, in the Mexican outbreak at least half the fatalities were in healthy young adults who succumbed to viral pneumonia, but the virus was and is still 'mild' for the most part, meaning that most people who catch it, including healthy young adults, will perhaps suffer a week of hell but then recover. And studies by Peter Palese and others have shown that the new virus is lacking in key protein components that are believed to determine or at least influence virulence. The question that really bugs me is whether the virus is starting to mutate into a much more virulent form, so that we will see many more fatalities proportionally than we are seeing now.
Just Wait and Watch
Could you comment on the Shanghai isolate? Thanks. See Recombinomics recent posting:
http://www.recombinomics.com/News/06180901/H1N1…
All the data on the effect of the PB2 E627K change on host range,
virulence, and temperature restriction have been acquired in animal
models or cell cultures. The observations with the 1918 strain and the
H7N7 death are associations, not proof of any causative role of the
E627K change. Whether or not PB2 E627K would lead to increased
virulence in humans is unknown and remains highly speculative. One way
to address this question would be to isolate the 2009 H1N1 virus from
cases of primary viral pneumonia, e.g. those where the virus has
replicated in the lower respiratory tract where the temperature is
higher than in the upper tract. The goal would be to determine if
replication in the lower tract is associated with the change E627K.
Other amino acid changes are likely to be involved. For example, there
is a recent report which concludes that “the E627K mutation of PB2 is
not an indispensable determinant in PB2 for mammalian adaptation by
H5N1 avian influenza virus”.
Rancaniello rocks! Thanks profrr.
If I were Vince, I would see if I could figure out a way to take his podcast team down to Sao Paulo for some personal investigation, and maybe a day on the beach.
Pingback: Riding the influenza pandemic wave
Pingback: TWiV 37: Open access
Pingback: SCIENCEPODCASTERS.ORG » This Week in Virology #37: Open Access
We don't know why apparently healthy people have influenza
complications. I suspect that many such individuals have slightly
sub-optimal immune responses that allow unchecked virus replication.
For example, the innate immune response (see previous posts at
virology blog) is crucial for blocking most virus infections; if a key
component of this system is slightly altered, lethal infections may
occur.
We don't know why apparently healthy people have influenza
complications. I suspect that many such individuals have slightly
sub-optimal immune responses that allow unchecked virus replication.
For example, the innate immune response (see previous posts at
virology blog) is crucial for blocking most virus infections; if a key
component of this system is slightly altered, lethal infections may
occur.