J. Virology: Genetics, Receptor Binding & Virulence (in Mice) Of Avian H10N8

Flu Virus binding to Receptor Cells – Credit CDC

 

# 9924

 

With all of the attention being given to the H7 and H5 avian flu strains this winter (see The Transmission Potential Of A(H7N9) In China & WHO: H5 Currently The Most Obvious Avian Flu Threat) it is easy to forget there are other avian subtypes on our radar as well. 

 

We’ve seen a handful of scattered H9N2 infections over the years, and even a one-off H6N1 in Taiwan in 2013. There’s a reservoir of mixed-host (avian, swine, equine, canine, etc.) H1, H2 & H3 viruses worthy of our attentions, as well.

 

But bringing up the rear are the H10 avian viruses, which have made a splash in the past few years.

 

Last fall, in Avian H10N7 Linked To Dead European Seals, we looked at the die off of thousands of harbor seals due to a combination of avian H10N7 influenza, pneumonia, and bacterial infection.  While known human infections with avian H10 viruses are limited, we’ve discussed them previously on several occasions. 

 

• In 2004, the first known human infections were reported among two Egyptian toddlers, as described in the  WHO/CDS/CSR/RMD report Avian Influenza Virus A (H10N7) Circulating among Humans in Egypt.
• And again, in 2012, in EID Journal: Human Infection With H10N7 Avian Influenza, we looked at a limited outbreak among workers with only mild symptoms at a chicken farm in Australia. 
• And perhaps most concerning, we saw three severe infections with an H10N8 virus in China last winter.

 

A little over a month ago, in TSRI: H10N8 and H6N1 Bind Poorly To Human Receptor Cells, we saw an encouraging report suggesting that neither subtype was poised to pose a serious pandemic threat, although they warned that these viruses bind differently than other avian viruses we’ve seen, and that our understanding of how these viruses mutate isn’t complete enough to warrant complacency.

 

All of which serves a prelude to a new study, published on April 8th in the Journal of Virology, that examines the genetic diversity, and behavior, of eight H10N8 viruses collected between 2009 and 2013. 

 

Worth noting:

• The genetic diversity (5 genotypes) detected among ducks and chickens
• Seven of the eight viruses replicated well in the lungs of mice
• Differences in virulence (in mice) between duck and chicken genotypes
• Dual binding to both Human (a2,6) and avian (a2,3) receptor cells, albeit with marked preference for avian receptors.
• The role that H9N2 has played in its evolution

 

The entire study, including an array of graphs and charts, is available at:

 

Genetics, receptor binding, and virulence in mice of H10N8 influenza viruses isolated from ducks and chickens in live poultry markets in China

Guohua Denga, Jianzhong Shia,  Jing Wanga, Huihui Konga,  Pengfei Cuia, Fang Zhanga,  Dan Tana, Yasuo Suzukib, Liling Liua, Yongping Jianga, Yuntao Guana and Hualan Chena⇑

ABSTRACT

We analyzed eight H10N8 viruses isolated from ducks and chickens in live poultry markets from 2009 to 2013 in China. These viruses showed distinct genetic diversity and formed five genotypes: the four duck isolates formed four different genotypes, whereas the four chicken viruses belong to a single genotype. The viruses bound to both human- and avian-type receptors, and four of the viruses caused 12.7% – 22.5% body weight loss in mice.

SUMMARY

In summary, our genetic studies indicate that the four duck viruses belong to four different genotypes, suggesting that they were introduced into ducks independently; the four chicken viruses belong to one genotype and appear to be hybrids of a duck virus and the local H9N2 viruses (Table 1).

The ability of H10N8 viruses to bind to human-type receptors facilitates their infection of humans, as occurred with the H7N9 viruses (28).

The more efficient replication in mice of the viruses isolated in Jiangxi province than the three duck viruses isolated in Hunan province suggests that the internal genes of the H9N2 viruses may have further increased the replicative ability and virulence of H10N8 viruses in mammals; of cause, the surface proteins may have also contributed to the difference of the virulence.

Although the viruses in our studies were all isolated from healthy birds, two H10 influenza viruses, A/turkey/England/384/79 and A/mandarin duck/Singapore/805/F-72/7/93, were reported to be highly pathogenic in chickens (3, 30). Therefore, it is important to continue monitoring the evolution of H10N8 influenza viruses and to evaluate their potential to cause disease in poultry and pandemics in humans.

 

As we’ve seen with the H5N1 and H7N9 viruses, H10N8 continues to evolve and the ubiquitous H9N2 virus appears to play a substantial role in its evolution.  An LPAI virus in chickens, H10N8 (like H7N9) can spread stealthily between flocks without the typical warning signs that HPAI viruses provide, making it more difficult to detect and eradicate.

 

While the general consensus is that the H10 family of avian viruses aren’t `ready for primetime’, H10N8 has already shown the ability to produce serious (even fatal) illness in humans, which elevates its profile when compared to many other less virulence avian strains.

 

Add in its growing genetic diversity, and its ability to reassort with other avian flu viruses, and H10N8 deservedly holds a second tier position on our list of avian flu viruses to watch.

J. Virol: Continued Reassortment Of Swine Flu Viruses With Genes From pH1N1 In China

 

# 8820

 

Big changes in influenza viruses – the kind that can create a novel, and potentially pandemic producing strain – come about through antigenic shift, also known as reassortment.  For shift to occur, two different flu strains must infect the same host simultaneously, and swap one or more gene segments.

 

Most reassortant viruses are evolutionary failures, but every once in awhile a more `fit’ virus emerges.

 

While seemingly an unlikely confluence of events – for pigs - who number in the millions, live in close quarters, have frequent contact with other pigs, birds, and humans, and who are notoriously susceptible to flu – shift happens with surprising frequency.

 

Since pigs can be infected by more than one flu virus at the same time, it is possible for two viruses to swap genetic material (reassort), resulting in a new hybrid strain.

 

Here in North America we’ve been watching the evolution of several swine variant viruses (H1N1v, H1N2v, H3N2v) over the past few years, all of which have reassorted with - and picked up the M gene segment from – the 2009 H1N1 virus (see Keeping Our Eyes On The Prize Pig).

 

Although reassortant flu viruses can emerge anywhere in the world (2009 H1N1 first emerged in North America), nowhere are pigs watched with more interest than in China, where huge populations of pigs are raised with frequent contact with other species, including humans.

 

Last year, in  EID Journal: Predicting Hotspots for Influenza Virus Reassortment, we saw China ranked as one of the globe’s top breeding grounds for new flu strains. 

 

Today we’ve a new paper, appearing in the Journal of Virology, that looks at the expanding diversity of reassorted swine flu viruses carrying genes from the 2009 H1N1 pandemic virus in Chinese pigs.  While the fully `humanized’ 2009 H1N1 virus doesn’t circulate in swine, researchers have isolated at least 17 reassortants  containing pH1N1-origin genes.

 

First the link and abstract, then I’ll have a bit more.

 

 

Expansion of genotypic diversity and establishment of 2009 H1N1 pandemic-origin internal genes in pigs in China

Huyi Lianga,b,c, Tommy Tsan-Yuk Lama,b,c, Xiaohui Fand, Xinchun Chena, Yu Zenga,c, Ji Zhoua,b,c, Lian Duana,b,c, Maying Tseb, Chung-Hei Chanb, Lifeng Lib,c, Tak-Ying Leungb, Chun-Hung Yipb, Chung-Lam Cheungb, Boping Zhoua, David K. Smithb,c, Leo Lit-Man Poona,b, Malik Peirisa,b, Yi Guana,b,c⇑ and Huachen Zhua,b,c⇑

ABSTRACT

‘Two-way' transmission of influenza viruses between humans and swine has been frequently observed and the occurrence of the 2009 H1N1 pandemic influenza (pdm/09) demonstrated that swine-origin viruses could facilitate the genesis of a pandemic strain. Although multiple introductions to and reassortment in swine of the pdm/09 virus have been repeatedly reported in both Eurasia and the Americas, its long-term impact on the development of swine influenza viruses (SIVs) has not been systematically explored. Our comprehensive evolutionary studies on the complete genomes of 387 SIVs obtained from 2009 to 2012 in influenza surveillance in China revealed 17 reassortant genotypes with pdm/09-origin genes.

Even though the entire 2009 pandemic virus and its surface genes cannot persist, its internal genes have becoming established and are now the predominant lineages in pigs in the region. The main persistent pdm/09-origin reassortant forms had at least 5 pdm/09-origin internal genes and their surface genes primarily of European avian-like (EA) or human H3N2-like SIV origin. These findings represent a marked change to the evolutionary patterns and ecosystem of SIVs in China. It is possible that the pdm/09-origin internal genes may be in the process of replacing EA- or triple reassortant-like internal genes. These alterations to the SIV gene pool need to be continually monitored to assess changes in the potential for SIVs to transmit to humans.

 

 

Remarkably, in less than five years, the swine influenza virus (SIV) gene pool in China has been dramatically re-invented with the internal genes derived from the pH1N1 virus now dominant, and continuing to expand. 

 

While their surface genes (HA & NA) remain more or less stable, the acquisition of as many as 5 internal genes from an already `humanized’  flu virus is of concern.

 

The authors write:

 

Over the survey period, these internal genes became predominant, potentially replacing those of the enzootic SIV lineages. The altered diversity of the SIV gene pool needs to be closely monitored for changes in the potential of SIVs to transmit to humans.

 

Although with the emergence of H7N9, H10N8, and H5N8 our attentions have been focused more on avian influenzas these past couple of years, in truth, a reassortant virus could emerge from practically any species susceptible to multiple flu strains (see Study: Dogs As Potential `Mixing Vessels’ For Influenza, mBio: A Mammalian Adapted H3N8 In Seals ).

 

Historically, avian and swine influenzas have a track record of producing pandemic strains, and so we tend to watch both arenas with particularly interest. 

 

For more on influenza reassortment, you may wish to revisit:

 

Viral Reassortants: Rocking The Cradle Of Influenza

Study: Novel & Variant Swine Influenzas In Korean Pigs

Seroprevalence Study: Avian Flu In Chinese Pigs

Study: Chikungunya’s Growing Threat To The Americas

One of two highly competent vectors in the Americas

 

# 8443

 

Up until about a decade ago,Chikungunya (CHKV) - a mosquito-borne virus - was only seen in central Africa.  In 2005 it jumped to  Reunion Island in the Indian Ocean, where it sparked a major epidemic infecting tens of thousands. Since then it has spread rapidly to counties such as India, Thailand, Vietnam, Indonesia, Myanmar, Pakistan, and others in  Asia and  the Western Pacific.

 

While rarely fatal, the CDC describes the symptoms of infection as lasting a few days to a few weeks, producing `debilitating illness, most often characterized by fever, headache, fatigue, nausea, vomiting, muscle pain, rash, and joint pain’,  although some may experience `incapacitating joint pain, or arthritis which may last for weeks or months.’ 

 

Last fall Chikungunya arrived in the Caribbean on the French part of St. Martins – but quickly spread to other islands in the Leeward and Windward chains - and has now appeared on the South American continent. This from the latest ECDC  Communicable Disease Threats Update:

 

Today, the American Society for Microbiology has published a press release warning that next month’s FIFA World Cup in Brazil, along with the presence of two very competent vectors (Aedes Aegypti & Aedes Albopictus mosquitoes) could help put the Chikungunya virus on a fast track to spreading across the Americas.

First some excerpts from the press release, as link to the study it references, then I’ll be back with a bit more.

 

7-Apr-2014

American Society for Microbiology

Chikungunya poised to invade the Americas

A team of French and Brazilian researchers warn that chikungunya virus is poised to invade, and become epidemic in the Americas according to research published ahead of print in the Journal of Virology.

The risk of a "catastrophic" epidemic in the Americas is boosted by the FIFA World Cup, to be held in Brazil next month, what with people coming in from near and from far, says corresponding author Ricardo Lourenco-de-Oliveira of the Instituto Oswaldo Cruz in Rio de Janeiro, Brazil. Brazil annually reports the highest incidence of dengue, a virus that is transmitted by Aedes aegypti and Aedes albopictus, the same mosquitoes that transmit chikungunya, he says.

The basis of his worries is the study, in which he and his collaborators compared the ability of 35 populations of the two Aedes species to transmit three different genotypes of chikungunya. These populations ranged all over the Americas from Buenos Aires to Tyson, Missouri (near St. Louis.) Even in temperate Missouri, A. albopictus was found to have a high dissemination and transmission ability for two of the three chikungunya genotypes.

(Continue . . . )

 

The study, which this press release references was published ahead of print in the online version of the Journal of Virology late last month.

 

High vector competence of Aedes aegypti and Aedes albopictus from ten American countries as a crucial factor of the spread of Chikungunya

Anubis Vega-Rúaa,b, Karima Zouachea, Romain Girodc, Anna-Bella Faillouxa* and Ricardo Lourenço-de-Oliveiraa,d*

IMPORTANCE Until recently, the Americas have never reported chikungunya (CHIK) autochthonous transmission despite its global expansion beginning in 2004. Large regions of the continent are highly infested with Ae. aegypti and Ae. albopictus and millions of dengue (DEN) cases are annually recorded. Indeed, DEN and CHIK viruses share the same vectors. Due to a recent CHIK outbreak affecting Caribbean islands, the need for a Pan-American evaluation of vector competence was compelling as a key parameter in assessing the epidemic risk. We demonstrated for the first time that Ae. aegypti and Ae. albopictus populations throughout the continent are highly competent to transmit CHIK irrespective to the viral genotypes tested. The risk of CHIK spreading throughout the tropical, subtropical and even temperate regions of the Americas is more than ever a reality. In light of our results, local authorities should immediately pursue and reinforce epidemiological and entomological surveillance to avoid a severe epidemic.

(Continue . . . )

 

Although the Aedes Aegypti mosquito is pretty much limited to the Gulf Coast states, the relatively recent introduction and growing geographic range of the Aedes Albopictus mosquito (see below) has raised concerns that once eradicated tropical diseases could become endemic across much of the US once more.

 

In 2009 the Natural Resources Defense Council (NRDC) released a report outlining the risks that Dengue (which relies on the same mosquito vectors as CHIKV) could re-establish itself in North America, that included this map showing the areas of the United States that are vulnerable to the introduction of Dengue.

Northern climes are far less likely to see DENV or CHIKV take hold than say, Florida or Southern Texas. Still, in the 18th and 19th century, both Malaria and Yellow Fever were endemic up and down the mid-Atlantic coast.

 

After an absence of 6 decades, Florida has reported sporadic locally acquired dengue cases over the past four years (see Florida: Dengue Forces Suspension Of Blood Donations In Two Counties), and just last year New York City reported a locally acquired case.

 

Perhaps a better example can be found in the West Nile Virus, which arrived in North America in 1997, and over the next five years managed to spread across much of the nation.

From the USGS Factsheet on West Nile Virus

Although West Nile Fever can often be mild, and is grossly underreported, in 2012 the CDC recorded the following statistics on human infection in the United States.

Final 2012 West Nile virus update:

In 2012, all 48 contiguous states, the District of Columbia, and Puerto Rico reported West Nile virus infections in people, birds, or mosquitoes. A total of 5,674 cases of West Nile virus disease in people, including 286 deaths, were reported to CDC. Of these, 2,873 (51%) were classified as neuroinvasive disease (such as meningitis or encephalitis) and 2,801 (49%) were classified as non-neuroinvasive disease. The numbers of neuroinvasive, non-neuroinvasive, and total West Nile virus disease cases reported in 2012 are the highest since 2003.

 

With summer temperatures rising across much of the United States, mosquito season cannot be far behind. So, if you live in, or are visiting one of these areas,  many health departments urge you to follow the `5 D’s’. 

Each summer we keep a close eye on the level of West Nile, EEE,  Dengue and other lesser known arboviruses in the United States.  This summer, and likely in summers to come, we are going to have to add Chikungunya to that list.

Two New Swine trH3N2 Studies To Ponder

 

 

# 6015

 

 

We’ve two studies to look at today focusing on the trH3N2 swine flu viruses that have been making headlines for several months; one appearing in the Journal of Virology and the other in the journal Eurosurveillance. 

 

First a recap of recent events.

 

Feel free to skip ahead if you are already up to speed on the history of this virus.

 

Excluding the 2009 `swine flu pandemic virus’, there have been 31 `novel’ swine flu infections detected in humans the United States since 2005.

 

Most appear to have been dead-end transmissions, and have come about from direct contact with pigs. The CDC believes only a few may have involved limited human-to-human transmission.

 

Up until last year, the most common strain of S-OIV (Swine-origin influenza virus) found in humans was a trH1N1 strain, but in 2010 we began to see a shift towards trH3N2 viruses.

 

This year, a new reassortant of trH3N2 has appeared on the scene that has picked up a the Matrix (M) gene segment from the 2009 H1N1 virus.

 

Reassorted viruses can result when two different flu strains inhabit the same host (human or otherwise) at the same time. Under the right conditions, they can swap one or more gene segments and produce a hybrid virus.

 

 

Unlike most of the earlier novel swine flu infections, this strain has shown increased signs of low level human-to-human transmission. You’ll find some recent coverage of this emerging swine flu variant in the following blogs:

 

Branswell On The New trH3N2 Flu Virus 

CIDRAP: New Details In The trH3N2 Story 

CDC Update On Iowa trH3N2 Cases

 

While only a small number of these reassorted trH3N2 viruses have been detected, the concern is, that over time it could get better at infecting humans and present a public health threat down the road.

 

 

All of which serves as prelude to today’s studies. 

 

First stop, a brief news summary by CIDRAP of a Journal of Virology article on recent H3N2 detections in Chinese pigs.

 

 

Novel reassortant H3N2 flu found in Chinese pigs

Chinese researchers have isolated three novel H3N2 reassortant viruses from pigs in southern China that contain genetic material from a pH1N1 strain, similar to those associated with 11 recent infections in US patients, according to a report yesterday in the Journal of Virology.

<SNIP>

 

In spite of their separation geographically and chronologically, they are genetically very closely related, the authors write. "This provides direct evidence that the pdm/09-like internal gene complex has been successfully incorporated into a swine H3N2 virus, and been prevalent in the pig population for a period of time," they add.

Dec 14 J Virol abstract

 

Most notable in this summary is that detections of novel trH3N2 viruses in Chinese pigs with the M gene from the pdmH1N1 strain go back well over a year.

 

Next stop, a report in Eurosurveillance that takes a detailed look at the genetic sequences, and evolution of this emerging trH3N2 virus.

 

 

S-OtrH3N2 viruses: use of sequence data for description of the molecular characteristics of the viruses and their relatedness to previously circulating H3N2 human viruses

Eurosurveillance, Volume 16, Issue 50, 15 December 2011

by B Lina, M Bouscambert, V Enouf, D Rousset, M Valette, S van der Werf

 

The authors conducted an analysis of hemagglutinin sequences (HA) from both human and swine-origin influenza A(H3N2) isolates and concluded that this new trH3N2 virus is most closely related (5.5% divergence) to the A/Wuhan/359/95 H3N2 strain that circulated in humans until the mid-1990s.

 

This strain was also incorporated into the seasonal flu shot as late as the 1997-98 northern hemisphere flu season.

 

Based on this study, they suggest that some degree of cross-protection is likely, particularly to those born before 1995.

 

They warn, however:

 

. . . it is impossible to predict if pre-existing immunity will be efficient against this virus, even if it seems likely that some cross-protection will exist; seroepidemiological surveys should be carried out to support or disprove this hypothesis.

 

The authors also express concerns over our current lab test’s ability to detect and identify these novel strains, stating that:

 

. . .  specific RT-PCR methods should be developed, or alternatively, predefined algorithms with already existing discriminating molecular tools need to be implemented.

 

Whether any of these novel swine viruses manages to adapt well enough to humans to pose a significant public health threat is something we will have to wait to see.

 

But even if these novel viruses fail to thrive - and end up as little more than a footnote in the history of influenza - they provide a stark reminder that influenza viruses are constantly evolving and mutating, looking for an evolutionary advantage.

 

We watch these novel viruses closely because history has shown that . . .  given enough time. 

 

They tend to find it.

 

D222G And Deep Lung Infections

 

 

 

# 5002

 

 

 

This morning we’ve a joint study from Imperial College London and the University of Marburg that may shed some light on why at least some cases of pandemic H1N1 proved severe (or fatal) while the great majority remained mild.

 

The `Norway’ or D222G (D225G in influenza H3 Numbering) mutation first announced by Norwegian Scientists last November has sparked repeated speculation that it might be associated with increased virulence.

 

Although we’ve covered this territory a number of times over the past year, a brief (and hopefully simple) review is in order. If you are up to speed on receptor binding, and the history of the D222G variant, feel free to skip the next section.

 

 

The D222G mutation had actually been detected months earlier, and in several other countries, but Norway was the first country to announce a possible link between that mutation and greater virulence.

 

This mutation involves a single amino acid change in the HA1 gene at position 222 from aspartic acid (D) to glycine (G).

 

The pdmH1N1 virus carrying this mutation appeared to bind more readily to receptor cells (α2-3) found deep in the lungs, whereas unmutated seasonal flu strains bind preferentially to the (α2-6) receptor cells found in the upper airway.

 

A virus’s ability to bind to specific cells is controlled by its RBD or Receptor Binding Domain; an area of its genetic code that allows it to attach to, and infect, specific types of host cells.

 

 

(A Very Simplified Illustration of RBDs)

 

Like a key into a padlock, the RBD must `fit’ in order to open the cell to infection.

 

For some deeper background you may wish to read Looking For the Sweet Spot, and a follow-up blog called Receptor Binding Domains:Take Two.

 

The World Health Organization’s take on this mutation has been that it is worth following, and studying, but there is no evidence (as yet) that it poses a substantial public health hazard.

 

In January, in a blog entitled WER Review: D222G Mutation In H1N1, I quoted the latest WHO report that stated:

 

`Based on currently available virological, epidemiological and clinical information, the D222G substitution does not appear to pose a major public health issue.’

 

This view is not universally held, however. There are some who have maintained that that the WHO is underestimating the impact of this mutation.

 

In March of this year, researchers from the Norwegian Institute of Public Health in Oslo reported that they found the mutation in 11 of 61 severe illness cases that they analyzed, but that it was not found in any of the 205 mild cases they looked at  (see CIDRAP Report On The H1N1 Mutation Debate).

 

The WHO WER Review reported that the overall prevalence of D222G was <1.8% (52 detections among >2755 HA sequences) in contrast to a rate of 7.1% in fatal cases.

 

The WHO paper also reported on the occurrence of  two other mutations at this amino acid position, D222E and D222N, although their significance is unclear.

 

While this all may sound like fairly damning evidence, it should be noted that mild cases have been detected with this D222G mutation in other studies, and many severe and fatal cases of pandemic H1N1 that have been examined did not have this mutation.

 

Some recent blogs on this mutation include:

 

Study: Receptor Binding Changes With H1N1 D222G Mutation

Eurosurveillance On Recently Isolated H1N1 Mutations

Referral: Virology Blog On D225G Mutation

 

 

Today’s study, which appears in the Journal of Virology, is called:

 

Altered receptor specificity and cell tropism of D222G haemagglutinin mutants from fatal cases of Pandemic A(H1N1) 2009 influenza

Yan Liu, Robert A. Childs, Tatyana Matrosovich, Stephen Wharton, Angelina S. Palma, Wengang Chai, Rodney Daniels, Victoria Gregory, Jennifer Uhlendorff, Makoto Kiso, Hans-Dieter Klenk, Alan Hay, Ten Feizi*, and Mikhail Matrosovich*

 

 

Admittedly a daunting title, but the abstract is a bit easier to follow.  I’ve re-paragraphed, and added a couple of highlights to it for readability.

 

Abstract

Mutations in the receptor-binding site of the haemagglutinin of pandemic influenza A(H1N1) 2009 viruses have been detected sporadically. An Asp222Gly (D222G) substitution has been associated with severe or fatal disease.

 

Here we show that 222G variants infected a higher proportion of ciliated cells in cultures of human airway epithelium than viruses with 222D or 222E which targeted mainly non-ciliated cells.

 

Carbohydrate microarray analyses showed that 222G variants bind a broader range of {alpha}2-3-linked sialyl receptor sequences of a type expressed on ciliated bronchial epithelial cells and on epithelia within the lung.

 

These features of 222G mutants may contribute to exacerbation of disease.

 

 

The discovery that D222G enhances the binding to ciliated cells is important because cilia are motile hair-like protuberances that line the airway and help move mucus (and debris) up and out of the lungs.

 

SEM micrograph of the cilia projecting from respiratory epithelium in the lungs

If you infect (and impair) the lung’s cilia, you (theoretically, at least) increase the odds of that person developing pneumonia.

 

In this study, researchers tested 6 different variants of the pdmH1N1 virus, including 3 (Lvi, Nor, Ham-E) with the D222G mutation.  

 

The `money quote’ from the study is:

 

The viruses with  222D  (Mol and Ham) and 222E  (Dak) showed a pattern of cell tropism typical of seasonal influenza A and B viruses  infecting predominantly non-ciliated cells known to be rich in α2-6 Sia sequence: less than 5% of infected cells were ciliated.

 

By contrast, the three viruses with 222G, Lvi, Nor and Ham-e, infected both ciliated and non-ciliated cells, and  20% or more of infected cells were ciliated, known to express α2-3 Sia sequences.

 

This change in the cell tropism, with a 5-10 fold increase in infection of ciliated cells, thus correlated with the presence of the D222G substitution in the HA, and other amino acid  differences, in particular D222E, had little or no effect.

 

 

Where then, does all of this leave us?

Well, the authors state that:

 

Whether the selection of the D222G mutation is a cause or a consequence of more severe lower respiratory tract infection has still to be resolved. It is evident, however, that its emergence is likely to exacerbate the severity of disease.

 

Luckily, this mutation has been slow to spread. 

 

It has been detected in less than 2% of the samples tested, and that suggests that (right now, anyway) it may be less fit for transmission than other competing strains.  

 

The fact that it tends to promote deep lung infections, and reduces the ability to expel mucus (and therefore cough productively), may help inhibit its spread.

 

A scenario not unlike what we’ve seen with the H5N1 (bird flu) virus, which as an avian virus, binds even more preferentially to α2-3 receptor cells. 

 

What is true today, however, may not hold true tomorrow. Influenza viruses are capable of swift and sometimes dramatic mutations. 

 

This research shows that even a seemingly mild strain of influenza can easily pick up virulence, and if it can retain transmissibility, could spark a serious public health hazard.

 

Which is why continued influenza research, the monitoring of this and other influenza strains, and the maintaining of pandemic readiness remain vital even after the pandemic of 2009 has passed.