Sequences from Tamiflu Resistant Immunocompromised Patients Released

[vinny]

Re: Sequences from Tamiflu Resistant Immunocompromised Patients Released

Apart from H274Y,what else would signal a major change in virulance of the virus,Dr Niman,thanks.

 

[HenryN]

Re: Sequences from Tamiflu Resistant Immunocompromised Patients Released

Apart from H274Y,what else would signal a major change in virulance of the virus,Dr Niman,thanks.

Explosion of cases in schools in south signals effective transmission.

 

[Toaster2]

Re: Sequences from Tamiflu Resistant Immunocompromised Patients Released

Slightly off topic maybe, but what do the sequences of HA so far tell us about the protective effect of the vaccines being made using seed strains from early on in the pandemic ?

 

[HenryN]

Re: Sequences from Tamiflu Resistant Immunocompromised Patients Released

Slightly off topic maybe, but what do the sequences of HA so far tell us about the protective effect of the vaccines being made using seed strains from early on in the pandemic ?

Drift has been slow, so matches to published sequences remains good.

 

[Toaster2]

Re: Sequences from Tamiflu Resistant Immunocompromised Patients Released

Drify has been slow, so matches to published sequences remains good.

That sounds good !

 

[HenryN]

Re: Sequences from Tamiflu Resistant Immunocompromised Patients Released

That sounds good !

Still first wave. More to come (including widespread H274Y).

 

[gsgs]

Re: Sequences from Tamiflu Resistant Immunocompromised Patients Released

I haven't yet looked at the sequences

how many days after infections were the samples taken
how many mutations

 

[HenryN]

Re: Sequences from Tamiflu Resistant Immunocompromised Patients Released

I appoligize for being so brief.

Washington/29 has a unique change in the NA segment that no other Swine Flu isolate has except for two Florida isolates. That change is a Proline at position 82.

So, I was simply attempting to clarify that while the two Washington isolates may in fact be "mixtures", and perhaps "share the same polymorphism", they are clearly not the same. In other words do not share all the same polymorphisms.

The fact that they share the same polymorphisms and they both have H274Y, yet they have distinguishing polymorphisms means that the H274Y was acquired EARLY (PRIOR to the distinguishing polymorphisms).

 

[Cyril]

Re: Sequences from Tamiflu Resistant Immunocompromised Patients Released

Looking at the nucleotides, as far as I can make out, the two of them can be traced back to Mexico/47N and Mexico/48N which are now that prevalent genotype in the state of Washington.

Washington/29 seems especially odd to me, with lots of polymorphisms, some of which trace to other strains but in a fashion that doesn't readily make sense.

There are typos in the sequences, so I guess we should take extra care.

 

[Cyril]

Re: Sequences from Tamiflu Resistant Immunocompromised Patients Released

Might not do you much good. As we are seeing indications of reinfection in mexico.

Any source on this I might check?

I had the general idea drift was due to human immunity exerting evolutionary pressure, which shouldn't apply to a 1st-wave pandemic virus. How could this happen?

 

[HenryN]

Re: Sequences from Tamiflu Resistant Immunocompromised Patients Released

Looking at the nucleotides, as far as I can make out, the two of them can be traced back to Mexico/47N and Mexico/48N which are now that prevalent genotype in the state of Washington.

Washington/29 seems especially odd to me, with lots of polymorphisms, some of which trace to other strains but in a fashion that doesn't readily make sense.

There are typos in the sequences, so I guess we should take extra care.

No, there are no "typos". The "typos" represent mixed signals. R standands for puRine (A and G). Y stands for pYrimindine (C and T). The sequences are mixtures and the R's and Y's represent mixed signals.

 

[HenryN]

Re: Sequences from Tamiflu Resistant Immunocompromised Patients Released

Looking at the nucleotides, as far as I can make out, the two of them can be traced back to Mexico/47N and Mexico/48N which are now that prevalent genotype in the state of Washington.

Washington/29 seems especially odd to me, with lots of polymorphisms, some of which trace to other strains but in a fashion that doesn't readily make sense.

There are typos in the sequences, so I guess we should take extra care.

<table border="0" cellpadding="0" cellspacing="10"><tbody><tr><th>Symbol</th><th>Meaning</th><th>Origin of designation</th></tr><tr><td align="middle">G</td><td align="middle">G</td><td align="middle">Guanine</td></tr><tr><td align="middle">A</td><td align="middle">A</td><td align="middle">Adenine</td></tr><tr><td align="middle">T</td><td align="middle">T</td><td align="middle">Thymine</td></tr><tr><td align="middle">C</td><td align="middle">C</td><td align="middle">Cytosine</td></tr><tr><td align="middle">R</td><td align="middle">G or A</td><td align="middle">puRine</td></tr><tr><td align="middle">Y</td><td align="middle">T or C</td><td align="middle">pYrimidine</td></tr><tr><td align="middle">M</td><td align="middle">A or C</td><td align="middle">aMino</td></tr><tr><td align="middle">K</td><td align="middle">G or T</td><td align="middle">Keto</td></tr><tr><td align="middle">S</td><td align="middle">G or C</td><td align="middle">Strong interaction (3 H bonds)</td></tr><tr><td align="middle">W</td><td align="middle">A or T</td><td align="middle">Weak interaction (2 H bonds)</td></tr><tr><td align="middle">H</td><td align="middle">A or C or T</td><td align="middle">not-G, H follows G in the alphabet</td></tr><tr><td align="middle">B</td><td align="middle">G or T or C</td><td align="middle">not-A, B follows A</td></tr><tr><td align="middle">V</td><td align="middle">G or C or A</td><td align="middle">not-T (not-U), V follows U</td></tr><tr><td align="middle">D</td><td align="middle">G or A or T</td><td align="middle">not-C, D follows C</td></tr><tr><td align="middle">N</td><td align="middle">G or A or T or C</td><td align="middle">aNy</td></tr></tbody></table>

 

[Cyril]

Re: Sequences from Tamiflu Resistant Immunocompromised Patients Released

Thanks for the explanation - and sorry for posting dumb. I'm not used to "low-level" genetics, and since those occurrences are not quite common I simply assumed anything beside ATCG would be a typo.

Guess I'm up for some reading

 

[HenryN]

Re: Sequences from Tamiflu Resistant Immunocompromised Patients Released

Thanks for the explanation - and sorry for posting dumb. I'm not used to "low-level" genetics, and since those occurrences are not quite common I simply assumed anything beside ATCG would be a typo.

Guess I'm up for some reading

Actually, I think a review is in order because mixtures are common, but represenattions in databases are FAR less common because of cloning as well as "consensus" sequences.

The Washington sequences are from an MMWR "dispatch" so they are actually sequences from uncloned samples, so they give a better representation of what was actually infecting the patients than the "cleaned up" view of reality, as indicated by most sequences in the data base. Moreover, since they are uncloned, even a consensus sequence can't get rid of mixtures that are close to 50/50, so there are "R's" and "Y's".

In summary, what is in the database is the sequencers EXTREMELY biased representation of "reality" (which is why the database does NOT have the vast majority of H274Y positive samples in which the H274Y is a minor component).

 

[gsgs]

Re: Sequences from Tamiflu Resistant Immunocompromised Patients Released

3 mutations in 29 in 14 days in HA and NA only.

4 times more than normal

 

[mixin]

Re: Sequences from Tamiflu Resistant Immunocompromised Patients Released

3 mutations in 29 in 14 days in HA and NA only.

4 times more than normal

Do you think that's because of the suppressed immune system, which gives the virus more time to pass through replication cycles?

 

[Mamabird]

Re: Sequences from Tamiflu Resistant Immunocompromised Patients Released

The fact that they share the same polymorphisms and they both have H274Y, yet they have distinguishing polymorphisms means that the H274Y was acquired EARLY (PRIOR to the distinguishing polymorphisms).

Interesting.

Would it be too much to ask for some description of the method that is used to not only understand how these polymorphisms are acquired, but the precise order of acquisition as well?

You seem to be the only person with the unique skill sets able to do this as far as I can tell.

 

[gsgs]

Re: Sequences from Tamiflu Resistant Immunocompromised Patients Released

when a mutation happens, then the number of old viruses
without the mutation is still much bigger than the mutated ones.
Only after some time (days,weeks) will the ratio become
1:1 or even more when there is selective advantage.

So, most mutations have a low chance to enter the next host.
This is different with prolonged infection.

There could be some other individual factors which lets a virus mutate more in some person

 

[HenryN]

Re: Sequences from Tamiflu Resistant Immunocompromised Patients Released

Interesting.

Would it be too much to ask for some description of the method that is used to not only understand how these polymorphisms are acquired, but the precise order of acquisition as well?

You seem to be the only person with the unique skill sets able to do this as far as I can tell.

Just do a phyogenetic tree. The poylmorphism at the base of the branch are early (and therefore in all branch members). Those are the tips are later and only in those at the tips. It's pretty straight forward.

 

[gsgs]

Re: Sequences from Tamiflu Resistant Immunocompromised Patients Released

when you have
--X--
--XY-
--XZ-

then X was probably earliest