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H5N1: A Rite Of Passage

 

 

 

 

# 5702

 

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Simplified Illustration of a Serial Passage Experiment. 

 

 

We’ve a study today that appeared recently in the Journal of Animal and Veterinary Advances that looks at increases in pathogenicity (in mice) of two H5N1 viruses after six serial passages in quail.

 

While the H5N1 virus remains primarily a disease of birds, concerns persist that the virus may someday acquire the ability to effectively infection – and transmit between – humans.


One of the primary barriers (but perhaps, not the only one) to this happening is the avian virus’s preference to bind to the type of receptor cells commonly found in the digestive and respiratory tracts of birds; alpha 2,3 receptor cells.

 

Human influenzas – on the other hand - are adapted to bind to the kind of receptor cells that line the surfaces of the human respiratory system; alpha 2,6 receptor cells.

 

Humans do have avian-like a2,3 receptor cells, but mainly deep in the lungs where it is difficult for the virus to reach.

 

There are some species that have an abundance of both types of receptor cells (most notably pigs, along with some varieties of poultry,the North American striped skunk, some small carnivores), and researchers worry that these could serve as `mixing vessels’ and give the virus an opportunity to adapt to the human receptor cells.

 

And according to today’s study, we can add quail to the list.

 

The study is called:

 

The Pathogenicity Variation of Two Quail-Origin H5N1 HPAV to BALB/c Mice after Six Passages in Quail

Hailiang Sun, Peirong Jiao, Yuqiang Cheng, Runyu Yuan, Pengfei Cui, Liming Jin, Chaoan Xin and Ming Liao

Abstract: H5N1 Highly Pathogenic Avian Influenza (HPAI) viruses have posed a serious threat to poultry, wild birds and mammals including humans since 1997. Quails are a potential reservoir in which influenza viruses might mutate to a mammalian transmissible form.

 

To investigate the molecular changes that occur in H5N1 HPAI viruses following passage in quail, two isolates, A/Quail/Guangdong/342/2008 (QL342) and A/Qquail/Guangdong/176/2004 (QL176) were selected. QL342 (clade 2.3.2) and QL176 (clade 7) viruses were high pathogenic to quail with a mortality rate of 18.3-100% and could be transmitted between naive contact quails.

 

After six passages in Japanese quails, researchers obtained two viruses, F6QL342 and F6QL176. Compared with QL342, F6QL342 had six animo acid substitutions in polymerases PB1 and PA, Nucleoprotein (NP) and Hemagglutinin (HA) but there was little difference in their pathogenicity to mice.

 

Compared with QL176, F6QL176 virus had 10 amino acid substitutions in PB2, NA, HA proteins. F6QL176 showed an increased pathogenicity towards mice causing more severe weight loss and higher lethality compared with QL176.

 

The findings showed that quails might play an important role in the adaptation of H5N1 avian influenza viruses to mammals. Therefore, researchers should enhance surveillance of H5N1 HPAI viruses in the quail population especially in live-bird markets.

 

The entire study is available HERE.

 

Essentially researchers infected a series of quail – taking the virus from one quail to the next – and then tested the viruses after six serial passages to see what, if any, changes to the virus had occurred.

 

The also tested the pathogenicity in mice of these viruses before and after the serial passage.

 

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Mice, while convenient to work with, are not the best substitutes for human physiology (they lack the a2,6 airway receptor cells). They are highly susceptible to H5N1, however, and are often used to determine the pathogenicity of avian influenza viruses in small mammals.

 

Genetic sequencing F6QL342 and F6QL176 end viruses showed that the receptor binding domain of the two viruses were unchanged after six passages in quails.

 

That doesn’t mean that it couldn’t happen.  Only that it didn’t happen in the course of this particular research project.

 

There were significant changes however, both in pathogenicity in mice, and amino acid substitutions.

 

The authors conclude:

 

CONCLUSION

This study suggested that avian influenza virus receptor-linked specificity could change by passages in the host in vivo. The researchers want to clarify if QL342 or QL176 had gained human receptor-linked specificity following passage in quails. However, the study showed that the amino acids present in the HA receptor-binding sites of the two viruses were not changed after six passages in quails.

 

Interestingly, the substitution N170D in HA protein in the F6Ql176 isolate resulted in the absence of a potential N-linked glycosylation site. Glycosylation can affect hemagglutinin receptor affinity and also the efficiency of release of new virus from host cells (Gallagher et al., 1992; Abe et al., 2004).

 

There were nine animo acids changes in NA and HA proteins from the F6Ql176 isolate that could potentially change the virus membrane characteristics.

 

 

Nature’s laboratory has unlimited time, no budgetary constraints, and a staggering array of hosts and pathogens to work with.

 

Which is why scientists like to remind us that `Nature always bats last’.

Related Post:

H5N1
Bird Flu
pathogenicity

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