Asymptomatic Pigs: Revisited

Credit Wikipedia

 

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A couple of months ago in EID Journal: Flu In Healthy-Looking Pigs we looked at a report indicating that it isn’t always possible to identify pigs carrying an influenza virus based simply on their appearance.

 

A dispatch from the EID Journal reported that nearly 1 in 5 healthy-looking pigs they tested at the Minnesota State Fair during the 2009 H1N1 influenza pandemic were actually infected with a flu virus.

 

This came out during the midst of several swine variant flu outbreaks this summer, involving several hundred people across 10 states. Viruses apparently contracted from pigs on display at local fairs (see MMWR: H3N2v Related Hospitalizations In Ohio – Summer 2012).

 

While fair officials were turning away pigs with overt signs of infection, this report suggested that perhaps those measures might not be sufficient.

 

Today, a pair of studies from Ohio State University -  one that finds a surprisingly large percentage of flu infected swine to be asymptomatic - and another that establishes just how closely linked the human and swine variant strains of influenza this summer really were.

 

In both cases, the lead author is Andrew Bowman, a  Ph.D. candidate in veterinary preventive medicine at Ohio State.

 

First, from the EID Journal, research that found more than 80% of the pigs that tested positive for influenza at the Ohio State fair between 2009 and 2011 showed no signs of illness.

 

Subclinical Influenza Virus A Infections in Pigs Exhibited at Agricultural Fairs, Ohio, USA, 2009–2011

Andrew S. Bowman , Jacqueline M. Nolting, Sarah W. Nelson, and Richard D. Slemons

Author affiliations: The Ohio State University, Columbus, Ohio, USA

Abstract

Agricultural fairs are associated with bidirectional, interspecies transmission of influenza virus A between humans and pigs. We examined pigs exhibited at agricultural fairs in Ohio during 2009–2011 for signs of influenza-like illness and collected nasal swab specimens from a representative subset of these animals.

 

Influenza virus A was recovered from pigs at 12/53 (22.6%) fairs during the 3-year sampling period. Pigs at 10/12 (83.3%) fairs from which influenza virus A was recovered did not show signs of influenza-like illness. Hemagglutinin, neuraminidase, and matrix gene combinations of the isolates were consistent with influenza virus A concurrently circulating among swine herds in the United States.

 

Subclinical influenza virus A infections in pigs at agricultural fairs may pose a risk to human health and create challenges for passive surveillance programs for influenza virus A in swine herds.

(Continue . . . )

 

 

 

Ohio State University has published a lengthy press release that discusses both papers.

 

Studies: Pigs Look Healthy But Test Positive for Flu at Fairs; Flu Transmission Seen Between Pigs and Humans

COLUMBUS, Ohio – More than 80 percent of pigs that tested positive for influenza A virus at Ohio county fairs between 2009 and 2011 showed no signs of illness, according to a new study.

 

Ohio State University researchers tested 20 pigs each at 53 fair events over those three summers and found at least one flu-positive pig at 12 fairs – almost a quarter of fairs tested.

 

The influenza strains identified in pigs in this study include H1N2 and H3N2 viruses – strains that have been circulating in pigs since 1998. In 2011, all of the H3N2 and H1N2 isolates found in pigs at the fairs contained a gene from the 2009 pandemic strain of H1N1, which is similar to the H3N2v strain causing human illness this year.

 

Though this finding alone is no cause for panic, it does show how quickly influenza viruses can change, said Andrew Bowman, lead author of the study and a Ph.D. candidate in veterinary preventive medicine at Ohio State.

 

In a second study led by Bowman, researchers compared the genomic sequences of influenza A viruses recovered in July 2012 from pigs and people. The analysis, showing a greater than 99 percent genetic similarity among the viruses, confirms that pigs and humans were infected with the same virus, indicating interspecies transmission.

(Continue . . .)

 

This second study appears in the journal Emerging Microbes & Infections.

 

Although the timing of the illnesses (and initial sub-typing) in humans and swine at the Ohio State Fair last July strongly suggested interspecies transmission, a >99% genomic match pretty much erases all doubt.

 

Molecular evidence for interspecies transmission of H3N2pM/H3N2v influenza A viruses at an Ohio agricultural fair, July 2012

Andrew S Bowman¹, Srinand Sreevatsan², Mary L Killian³, Shannon L Page⁴, Sarah W Nelson¹, Jacqueline M Nolting¹, Carol Cardona² and Richard D Slemons¹

 

Evidence accumulating in 2011–2012 indicates that there is significant intra- and inter-species transmission of influenza A viruses at agricultural fairs, which has renewed interest in this unique human/swine interface.

 

Six human cases of influenza A (H3N2) variant (H3N2v) virus infections were epidemiologically linked to swine exposure at fairs in the United States in 2011. In 2012, the number of H3N2v cases in the Midwest had exceeded 300 from early July to September, 2012.

 

Prospective influenza A virus surveillance among pigs at Ohio fairs resulted in the detection of H3N2pM (H3N2 influenza A viruses containing the matrix (M) gene from the influenza A (H1N1) pdm09 virus). These H3N2pM viruses were temporally and spatially linked to several human H3N2v cases.

 

Complete genomic analyses of these H3N2pM isolates demonstrated >99% nucleotide similarity to the H3N2v isolates recovered from human cases. Actions to mitigate the bidirectional interspecies transmission of influenza A virus between people and animals at agricultural fairs may be warranted.

(Continue . . .)

 

 

While the vast majority of the swine-to-human flu transmissions this year have involved the H3N2v virus, as you can see from the following table, small number of H1N1v and H1N2v infections have been reported as well. 

 

 

Given the limits of surveillance, testing, and reporting – we really don’t know what the normal `background rate’ of these types of novel flu infections are in humans.

 

The smattering of reports since 2005 indicate they may be fairly rare, but are certainly not unheard of.

 

The majority of human swine variant flu infections this summer were relatively mild (out of 300+ infections, 16 were hospitalized, and 1 died), but it is always of concern anytime a novel influenza virus jumps from another species to humans.

 

Each time a novel flu jumps from a pig to a human it gives the virus another opportunity to adapt to human physiology. The CDC’s most recent assessment on the H3N2v virus reads:

 

It's possible that sporadic infections and even localized outbreaks among people with this virus will continue to occur.

While there is no evidence at this time that sustained human-to-human transmission is occurring, all influenza viruses have the capacity to change and it's possible that this virus may become widespread.

 

So far, the severity of illnesses associated with this virus in people has been similar to the severity of illnesses associated with seasonal flu virus infections. Limited serologic studies indicate that adults may have some pre-existing immunity to this virus while children do not.

 

CDC is closely monitoring human infections with all novel influenza viruses, including H3N2v viruses, and will provide more information as it becomes available.

 

 

With further evidence of asymptomatic influenza infection in pigs, fair officials and public health agencies will need to decide on the best policies to limit future exchanges (in either direction) of flu viruses between people and pigs.

»» Read More

SARS Virus Placed On Select Agents List

 

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A story this morning from Helen Branswell of the Canadian Press on new regulations for working with the SARS virus, but first, a little background.

 

In May of 1995 a lab technician from Lancaster, Ohio – using a credit card and and a fake letterhead – ordered a quantity of Yersinia pestis (the bacteria that causes plague) from a mail order biomedical supply firm in Maryland.

 

Although 3 vials were shipped to him, the company grew suspicious and alerted federal authorities. He was eventually convicted of mail fraud – and placed on 18 months probation - since he misrepresented himself as working for a government laboratory.

 

Around the same time, halfway around the world, a Japanese cult called Aum Shinrikyo unleashed a Sarin gas attack on five subway trains in Tokyo. In all - 13 people were killed, another 54 serious injured – while hundreds more were affected.

 

When the cult’s headquarters was raided, police reported finding explosives, along with  chemical and biological agents, including  anthrax and Ebola cultures.

 

Suddenly, the threat of homegrown biological terrorism had grown very real. In response, Congress passed Section 511 of the Antiterrorism and Effective Death Penalty of 1996.

 

This legislation was the first step on the road to creating the CDC’s Select Agent Program, which today `oversees the activities of possession of biological agents and toxins that have the potential to pose a severe threat to public, animal or plant health, or to animal or plant products’

 

For more, we go to the CDC’s Select Agent Program Brochure.

 

This Act directed the U.S. Department of Health and Human Services (HHS) to establish a list of biological agents and toxins that could threaten public health and safety, procedures for governing the transfer of those agents, and training requirements for entities working with these “select agents.”

HHS delegated the authority to implement this Act to the Centers for Disease Control and Prevention (CDC), which then established the CDC Select Agent Program. The Division of Select Agents and Toxins in the CDC Office of Public Health Preparedness and Response oversees this program.

9/11 and increased regulation of select agents

Following the anthrax attacks of 2001, Congress significantly strengthened oversight of select agents by passing the following acts:

• USA PATRIOT Act (Uniting and Strengthening America by Providing Appropriate Tools Required to Intercept and Obstruct Terrorism Act of 2001; Public Law 107-56): Restricted  access to select agents
  
• Bioterrorism Act (Public Health Security and Bioterrorism Preparedness and Response Act of 2002; Public Law 107-188): Increased safeguards and security measures as well as oversight of the possession and use of select agents

 

Essentially, in order to be able to acquire or work with certain toxins and biological agents, you had to be registered and approved entity by the HHS.

 

 

Fast forward to this past week – when by chance, a SARS-like coronavirus detected in two patients from the Middle East was making big news – and two years after it was first requested by the CDC, the SARS virus was added to the Select Agents list.

Here is the story from Helen Branswell, that also has details on how Canada deals with these types of biological materials, and some quotes from Michael Osterholm of CIDRAP.

 

U.S. government names SARS a select agent, restricting labs that work on virus

Friday, 05 October 2012 02:15 Helen Branswell, The Canadian Press

The Centers for Disease Control has added SARS to the list of select agents in the United States, a move designed to try to ensure the virus stays within the confines of highly regulated laboratories.

 

The addition, which the CDC first proposed over two years ago, was given legal status this week when the revised select agent list was published in the U.S. Federal Registry.

 

The timing of the move is both ironic and co-incidental.

(Continue . . .)

 

Although the SARS epidemic of 2002-2003 was eventually brought under control, the virus infected roughly 8,000 people, killing nearly 800. 

 

Since then, while there have been no recurrences from the wild, three separate lab accidents in 2003 and 2004 resulted in the infection of at least 13 people.

 

SARS, or a variation on the SARS-Coronavirus, could wreak havoc were it to emerge once more from the wild, or be accidentally (or intentionally) released.

 

And many worry that - with the technology of today – cheaper, faster, and more capable than anything that could be imagined back in 1995, the ability of malevolent bio-hackers working out of their basements to create new, and dangerous organisms has never been greater.

 

While once we only had to worry about nature serving up an occasional biological curve ball, increasingly that ability – by design or by error - is becoming available to human hands all around the world.

 

Which makes the regulation and control of the most dangerous of these toxins and biological organisms a top priority of many governments around the world.

»» Read More

NIH Video: Dual Use Research Of Concern (DURC)

 

NIH Brochure on Dual Use Research

 

# 6264

 

 

Over the past few months an obscure acronym has made it’s way into numerous blogs, news headlines, and even popular usage; DURC -  Dual Use Research of Concern.

 

While it is the current debate over controversial H5N1 transmissibility studies that has prompted its emergence (see The Biosecurity Debate On H5N1 Research), DURC has been a matter of national concern for a number of years.

 

The NIH produced a 7 minute video in 2010 highlighting the concerns of DURC, called Dual Use Research: A dialogue.  Click the link, or the image below to watch.

 

 

 

Last week the  Office of Science Policy at the NIH released a 4 page set of guidelines for DURC (Duel Use Research of Concern) projects designed to beef up oversight and biosecurity of U.S. funded projects.

 

The scope of this new policy is to cover research on the most dangerous of biological organisms, listing;

 

a)  Avian influenza virus (highly pathogenic) 
b)  Bacillus anthracis
c)  Botulinum neurotoxin
d)  Burkholderia mallei
e)  Burkholderia pseudomallei
f)  Ebola virus
g)  Foot-and-mouth disease virus
h)  Francisella tularensis
i)  Marburg virus

j)  Reconstructed 1918 Influenza virus

k)  Rinderpest virus
l)  Toxin-producing strains of Clostridium botulinum
m) Variola major virus
n)  Variola minor virus
o)  Yersinia pestis

 

Specifically any research that seeks to:

 

a)  Enhances the harmful consequences of the agent or toxin; 

b)  Disrupts immunity or the effectiveness of an immunization against the agent or toxin without
clinical or agricultural justification;

c)  Confers to the  agent or toxin resistance to clinically or agriculturally useful prophylactic or
therapeutic interventions against that agent or toxin or facilitates their ability to evade detection methodologies;

d)  Increases the stability, transmissibility, or the ability to disseminate the agent or toxin; 

e)  Alters the host range or tropism of the agent or toxin;  

f)  Enhances the susceptibility of a host population to the agent or toxin; or

g)  Generates or reconstitutes an eradicated or extinct agent or toxin listed in Section (III.1) above.

 

 

For more on DURC, the NSABB, and the Office of Biotechnology Activities, you may wish to visit the following links.

Brochure on Dual Use Research

Video on Dual Use Research

International Meetings

NSABB FAQs

Summary of NSABB Reports and Activities

Responsible Communication of Life Sciences Research with Dual Use Potential

Global Status of Strategies for Addressing the Intersection of Science and Security

Roundtable at the ASM Biodefense and Emerging Diseases Research meeting

»» Read More

Another Entry Into The H5N1 Lethality Debate

 

 

 

# 6215

 

 

With the announcement last fall that two researchers had successfully created a ferret-transmissible (and in one case, lethal), version of the H5N1 virus there have been fresh calls to regulate and restrict just how, and where, this sort of research should be conducted.

 

While not guaranteed - successful adaptation to ferrets (which have respiratory systems similar to humans) is assumed by many researchers to be a pretty good indication it would transmit in humans as well.

 

Suddenly labs that have been working with variants of the H5N1 virus are under new scrutiny, and regulators are questioning just how much biosecurity is needed to work on these viruses.

 

Last month Canada decided to restrict H5N1 research to labs with the highest biosecurity measures (see  Canada Issues Biosafety Advisory For H5N1 Research), and other countries are considering similar measures.

 

In an attempt to assuage fears over the risks of H5N1 research (and the publication of the results), several well respected scientists have challenged the notion that the bird flu virus is as lethal in humans as is commonly portrayed.

 

One high profile paper appeared in Science last month -Seroevidence for H5N1 Influenza Infections in Humans: Meta-analysis - authored by Professor Peter Palese et. al., that argues that we are likely missing a great many uncounted H5N1 infections, and that the virus is far less lethal than has been assumed in the past.

 

This is similar to the argument that Vincent Racaniello offered last January in his blog Should we fear avian H5N1 influenza?

 

While stating that we don’t have definitive numbers, Palese writes that if one assumes a 1-2% infection rate among exposed populations, there would likely be millions of people who have been infected by the H5N1 virus.

 

Palese grants that deaths from the virus may also be undercounted, and calls for better studies (something that I think everyone, regardless of where they stand on this issue, would agree with).

 

A counter argument appeared last month in mBio, authored by CIDRAP director Michael T. Osterholm and Nick Kelley. 

 

They found little evidence to support the notion that we are missing `millions’ of uncounted H5N1 infections (see mBio: Mammalian-Transmissible H5N1 Influenza: Facts and Perspective), and find that the H5N1 virus has the potential to be highly virulent in humans.

 

 

Mammalian-Transmissible H5N1 Influenza: Facts and Perspective

Michael T. Osterholm Nicholas S. Kelley

 

All of which serves as prelude to a new analysis, authored by Eric S. Toner and Amesh A. Adalja (both of the Center for Biosecurity at the University of Pittsburgh Medical Center (UPMC)) published last week in Biosecurity and Bioterrorism: Biodefense Strategy, Practice, and Science.

 

Is H5N1 Really Highly Lethal?

Eric S. Toner and Amesh A. Adalja.

Biosecurity and Bioterrorism: Biodefense Strategy, Practice, and Science. doi:10.1089/bsp.2012.022

 

I would invite you to read the entire study (it is reasonably short), but an excerpt from the press release sums it up nicely:

 

The authors review the available evidence: the distinctions between different clades of H5N1, the clinical series of human H5N1 cases, and the seroepidemiological and laboratory studies. They conclude that the preponderance of evidence argues that H5N1 virus is indeed highly lethal in humans compared to other influenza viruses.

 

Author Eric Toner said, “Our review of the evidence underscores what so many experts have been saying for years: Wild-type H5N1 is a very dangerous virus. We are quite fortunate it has not yet become contagious between humans.”

 

 

Dueling opinion pieces obviously won’t settle this argument, and regrettably, the amount of hard data available to support either position is limited.

 

While I suspect the virus is less deadly than the `official numbers’ suggest  - given the stakes - it would seem to this humble blogger that if we err, we ought to err in favor of overestimating the threat of this virus.

 

At least in the short run.

 

We can always relax policies later when we have more accurate data and a better handle on the threat. 

 

 

But underestimating this virus now, before we have solid answers, could lead to an irrevocable error.

»» Read More

mBio: The H5N1 Biosafety Level Debate

 

UPDATED: mBio has published4 editorial/commentary pieces on the H5N1 research debate.  I’ve posted the links at the bottom of this blog post.

 

 

 

# 6197

 

 

Later today mBio will publish a pair of opposing views on what level of  laboratory biosecurity (BSL-3 or BSL-4) should be required in order to work on the H5N1 virus.

 

While there are many differences in procedures between them, in the broadest definition under BSL-3 it is the pathogen that is kept isolated, and worked on in specially designed negative airflow biological safety cabinets (BSC). Lab personnel wear fairly standard PPEs (Personal Protective Equipment) in BSL-3 labs.

 

With enhanced BSL-4 security, the focus is on isolating and protecting lab workers from the pathogen, and so they must all wear fully contained BSL-4 `space suits’, and decontaminate before leaving the work area.

 

BSL-4 labs work on the most dangerous pathogens that pose a particularly high risk of infection, such as Marburg, Ebola, Lassa fever, CCHF, and smallpox.

 

BSL-4 labs are far more expensive to build and maintain than BSL-3 facilities, and there are not nearly as many of them around the world.

 

Which presents a dilemma.  If you restrict work on the H5N1 virus to only BSL-4 labs, that would exclude many universities (and even entire countries) from being able to conduct research on the virus.

 

You may recall that early in February Canada restricted H5N1 research to BSL-4 facilities (see  Canada Issues Biosafety Advisory For H5N1 Research).

 

Although the mBio articles won’t be published for a few more hours, we’ve got a press release with some of the details and a preview by Helen Branswell.

First stop, the press release from the American Society for Microbiology

 

New H5N1 viruses: How to balance risk of escape with benefits of research?

In the controversy surrounding the newly developed strains of avian H5N1 flu viruses, scientists and policy makers are struggling with one question in particular: what level of biosafety is best for studying these potentially lethal strains of influenza? In a pair of commentaries, researchers from the Mount Sinai School of Medicine in New York and the University of Michigan argue their different views of how to safely handle H5N1 flu viruses. The commentaries will be published in mBio®, the online open-access journal of the American Society for Microbiology, on Tuesday, March 6.

 

This fall, the U.S. National Science Advisory Board for Biosecurity (NSABB) set off a debate when it asked the authors of two recent H5N1 research studies and the scientific journals that planned to publish them to withhold crucial details of the research in the interest of biosecurity. The researchers had taken H5N1, a virus that cannot easily transmit from human to human, and developed strains of the virus that can transmit easily between ferrets, which are a common model for human influenza.

 

These H5N1 strains and others like them that might be developed in the future could pose a grave threat to human life, but researchers and others argue that studying these H5N1 strains could help bolster preparedness efforts and vaccine development to help fend off a potential H5N1 pandemic. How can we balance the need to protect human life from the accidental escape of an H5N1 strain with the need to continue research that might prevent a naturally occurring outbreak? Which biosafety level (BSL) is right for the H5N1 virus?

 

In the commentaries appearing in mBio, two experts offer opposing views of the appropriate level of security for dealing with H5N1 viruses. The authors agree that, with a reported case fatality rate that could be as high as 50% or more, H5N1 could create a pandemic of disastrous proportions, but they differ in their opinions of how to strike a balance between biosecurity and potentially life-saving research.

(Continue . . . )

 

Next up, from the Canadian Press, a preview from Helen Branswell.

 

The Canadian Press - ONLINE EDITION

Future work on lab-made bird flu viruses should be done in most secure labs

By: Helen Branswell, The Canadian Press

Posted: 03/6/2012 3:02 AM TORONTO - Future work on mutated bird flu viruses should only take place in laboratories with the highest level of biosafety, suggests a new commentary on the controversy over two studies that led to the creation of these viruses.

 

But an opposing view argues that to restrict work on the viruses to so-called BSL4 labs would not leave the world safer, but would impede the quest to find out how flu viruses that normally infect birds can adapt to infect people.

(Continue . . .)

 

Both opinion pieces should be online at 10am EST, March 6th, and available at this link.

 

Mammalian-Transmissible H5N1 Virus: Containment Level and Case Fatality Ratio

Arturo Casadevall and Thomas Shenk

doi:10.1128/mBio.00054-12

 

Working Safely with H5N1 Viruses

Adolfo García-Sastre

doi:10.1128/mBio.00049-12

 

Biosafety Considerations of Mammalian-Transmissible H5N1 Influenza

Michael J. Imperiale and Michael G. Hanna III

doi:10.1128/mBio.00043-12

 

Ferret-Transmissible Influenza A(H5N1) Virus: Let Us Err on the Side of Caution

Lisa N. Murillo

doi:10.1128/mBio.00037-12

»» Read More

The Biosecurity Debate On H5N1 Research

 

BSL-4 Lab Worker - Photo Credit –USAMRIID

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Three months ago, one of the best known researchers in the world - Ron Fouchier of Erasmus Medical Centre in Rotterdam - announced at a scientific conference that he’d managed to turn H5N1 into a virulent, and easily transmissible (among ferrets, anyway) pathogen.

 

(You can read about this work in Katherine Harmon’s Sci-Am article and in a follow up to this story in New Scientist: Five Easy Mutations.)

 

Halfway across the world, Yoshihiro Kawaoka, a highly respected virologist at the University of Wisconsin-Madison School of Veterinary Medicine announced the creation of a comparable H5N1 super flu at roughly the same time.

 

At issue is whether scientists should even be tinkering with this particularly lethal flu strain, and whether (or how) those results should be published.

 

Some fear that this knowledge could be used by bioterrorists to engineer a bio-weapon (see NPR: Bio-Terrorism Concerns Over Bird Flu Research).

 

Erasmus University provided their side of this discussion late last month, which I blogged on in The Bird Flu Research Debate Continues.

 

On Thursday I highlighted an opinion piece (see Laurie Garrett On The Bird Flu Research Controversy) that appeared in Foreign Policy, that essentially argued that in many ways the genie was already out of the bottle, and that if we didn’t figure out this virus, nature could very well do it for us. 

 

The Center For Biosecurity at UPMC, on the same day, released a strongly worded editorial advising against these types of H5N1 research projects, and lobbying against the publication of the methods and results.

 

The link to the Biosecurity Blog follows:

 

 

Editorial: The Risk of Engineering a Highly Transmissible H5N1 Virus.

Thomas V. Inglesby, Anita Cicero, D. A. Henderson. Scientists recently have announced that they genetically modified H5N1 in the laboratory and that this mutated strain spread through the air between ferrets that were physically separated from each other. This is ominous news . . . Read editorial now [Posted December 15, 2011]

 

The Center’s director - and one of the authors of this editorial - Thomas V. Inglesby appeared on NBC Nightly News Thursday night in a short segment on this controversy.

 

I don’t know how long this link will be active, but for now you can Watch this clip from the December 15 broadcast.

 

 

I confess to having mixed feelings over all of this, but I suspect that ultimately, some sort of redacted version of these research projects will make it into print.

 

The fact that two scientists – half a world apart –independently created a virulent and transmissible H5N1 flu suggests that the basic knowledge on how to do so is already in the ether.

 

The work of Fouchier and Kawaoka are under intense scrutiny right now because those experiments yielded unexpected success.

 

But they aren’t the only scientists following these controversial avenues of research.

 

And in the case of the Fouchier experiment, it wasn’t sophisticated genetic engineering that produced this super flu, it was the low-tech (and well known) serial passage method that ultimately succeeded.

 

Last July, in H5N1: A Rite Of Passage I looked at another bird flu research project that looked at increases in pathogenicity (in mice) of two H5N1 viruses after six serial passages in quail.

 

Simplified Illustration of a Serial Passage Experiment

 

 

Similarly, last September we saw a study that appeared in The Journal of Virology called:

 

Increased pathogenicity of a reassortant 2009 pandemic H1N1 influenza virus containing an H5N1 hemagglutinin

J. Virol. doi:10.1128/JVI.05582-11

Troy D. Cline, Erik A. Karlsson, Pamela Freiden, Bradley J. Seufzer, Jerold E. Rehg, Richard J. Webby, and Stacey Schultz-Cherry

 

Using reverse genetics, researchers at St. Jude Children’s Research Hospital created several reassortant 2009 pH1N1 viruses with individual genes borrowed from a 1997 H5N1 virus, and then tested them for replication and virulence.

 

They found that one of these lab-created viruses, with the HA gene from the H5 virus, increased replication over the parental strain and produced virulence in mice comparable to the parent H5N1 strain.

 

They also report that serial passage through human lung epithelial cells (in Vitro) "resulted in increased pathogenicity, suggesting that these viruses may easily adapt to humans and become more virulent."

 

And while not (currently) in the same league as H5N1 when it comes to pathogenicity, similar experiments are being performed on the H9N2 avian flu virus as well.

 

Last February in PNAS: Reassortment Of H1N1 And H9N2 Avian viruses we saw research from Chinese scientists that created – using reverse genetics – 128 reassorted viruses from the avian H9N2 virus and the (formerly pandemic) H1N1 virus.

 

In mouse testing, they found half of the hybrid viruses were biologically `fit’ as far as replication goes, and 8 hybrids were significantly more pathogenic than either of their parental viruses.

 

And in July of this year, another H9N2 reassortment study appeared in PNAS, where scientists combined the H9N2 virus with the 2009 H1N1 virus, and generated 4 reassortants (PNAS: Reassortment Potential Of Avian H9N2). 

 

Three of these hybrid viruses showed efficient respiratory droplet transmission, suggestive that if this reassortment can be induced in the lab, it has the potential of occurring in nature.

 

These are but a few examples of the kind of reverse genetics research being performed on flu viruses in laboratories all over the world. 

 

While all of this may be more than a little unnerving, quashing the publication of Fouchier’s or Kawaoka’s research isn’t going to stop other scientists, in hundreds of labs around the world, from pushing forward with their research.

 

Added to that, nature’s laboratory is open 24/7, working to solve the puzzle of how to make the highly lethal H5N1 virus a more `biologically fit’ pathogen. 

 

And for a virus, that means transmissibility.

 

Something which research scientists hope they can mitigate or even halt, if they can figure out – in advance – how nature will go about it.

 

Which, if they are right, could bring  a whole new meaning to the phrase `Publish or Perish’.

 

»» Read More