Scientists create hybrid flu that can go airborne

As the world is transfixed by a new H7N9 bird flu virus spreading through China, a study reminds us that a different avian influenza — H5N1 — still poses a pandemic threat.

A team of scientists in China has created hybrid viruses by mixing genes from H5N1 and the H1N1 strain behind the 2009 swine flu pandemic, and showed that some of the hybrids can spread through the air between guinea pigs. The results are published in Science¹.

Flu hybrids can arise naturally when two viral strains infect the same cell and exchange genes. This process, known as reassortment, produced the strains responsible for at least three past flu pandemics, including the one in 2009.

There is no evidence that H5N1 and H1N1 have reassorted naturally yet, but they have many opportunities to do so. The viruses overlap both in their geographical range and in the species they infect, and although H5N1 tends mostly to swap genes in its own lineage, the pandemic H1N1 strain seems to be particularly prone to reassortment.

“If these mammalian-transmissible H5N1 viruses are generated in nature, a pandemic will be highly likely,” says Hualan Chen, a virologist at the Harbin Veterinary Research Institute of the Chinese Academy of Sciences, who led the study.

“It’s remarkable work and clearly shows how the continued circulation of H5N1 strains in Asia and Egypt continues to pose a very real threat for human and animal health,” says Jeremy Farrar, director of the Oxford University Clinical Research Unit in Ho Chi Minh City, Vietnam.

Flu fears

Chen’s results are likely to reignite the controversy that plagued the flu community last year, when two groups found that H5N1 could go airborne if it carried certain mutations in a gene that produced a protein called haemagglutinin (HA)^{2, 3}. Following heated debate over biosecurity issues raised by the work, the flu community instigated a voluntary year-long moratorium on research that would produce further transmissible strains. Chen’s experiments were all finished before the hiatus came into effect, but more work of this nature can be expected now that the moratorium has been lifted.

“I do believe such research is critical to our understanding of influenza,” says Farrar. “But such work, anywhere in the world, needs to be tightly regulated and conducted in the most secure facilities, which are registered and certified to a common international standard.”

Virologists have created H5N1 reassortants before. One study found that H5N1 did not produce transmissible hybrids when it reassorts with a flu strain called H3N2⁴. But in 2011, Stacey Schultz-Cherry, a virologist at St. Jude Children’s Research Hospital in Memphis, Tennessee, showed that pandemic H1N1 becomes more virulent if it carries the HA gene from H5N1⁵.

Chen’s team mixed and matched seven gene segments from H5N1 and H1N1 in every possible combination, to create 127 reassortant viruses, all with H5N1’s HA gene. Some of these hybrids could spread through the air between guinea pigs in adjacent cages, as long as they carried either or both of two genes from H1N1 called PA and NS. Two further genes from H1N1, NA and M, promoted airborne transmission to a lesser extent, and another, the NP gene, did so in combination with PA.

“It’s a very extensive paper,” says Schultz-Cherry. “It really shows that it’s more than just the HA. The other proteins are just as important and can drive transmission.” Chen says that health organisations should monitor wild viruses for the gene combinations that her team identified in the latest study. “If those kinds of reassortants are found, we’d need to pay high attention.”

Knowledge gap

It is unclear how the results apply to humans. Guinea pigs have bird-like receptor proteins in their upper airways in addition to mammalian ones, so reassortant viruses might bind in them more easily than they would in humans.

And scientists do not know whether the hybrid viruses are as deadly as the parent H5N1. The hybrids did not kill any of the guinea pigs they spread to, but Chen says that these rodents are not good models for pathogenicity in humans.

There is also a chance that worldwide exposure that already occurred to the pandemic H1N1 strain might actually mitigate the risk of a future pandemic by providing people with some immunity against reassortants with H5N1. In an earlier study, Chen and her colleagues showed that a vaccine made from pandemic H1N1 provided some protection against H5N1 infections in mice⁶.

“If you take [antibodies] from people who have been vaccinated or naturally infected, will they cross-react with these viruses?” asks Schultz-Cherry. “That’s an important study that would need to be done.”

Ironically, Chen’s team is now too busy reacting to the emerging threat of a different bird flu — H7N9. Research on H5N1 will have to wait.

New deadly bird flu virus infects at least 20 in China

The World Health Organization is talking with the Chinese government about sending international experts to China to help investigate a new bird flu strain that has sickened at least 24 people, killing seven of them.

A 64-year-old retired man in Shanghai became the latest victim of the H7N9 bird flu virus that had previously not been known to infect humans, the city government said Monday.

The Shanghai government said the man died Sunday night, a week after first experiencing chills. He sought medical treatment last Wednesday for pneumonia-like conditions. By Sunday morning, his condition worsened, he was out of breath and was admitted to a ward for in-patient treatment. He died hours later.

Michael O’Leary, head of WHO’s office in China, told reporters in Beijing on Monday that the international health organization had confidence in China’s efforts to track and control the outbreak of H7N9 infections, but that growing interest in the virus globally has prompted WHO to consider sending a team.

The cases are of “great interest not only in the scientific community but in the world at large,” O’Leary said at a joint press conference with China’s national health agency. “WHO’s responsibility in part is to make sure that we serve as liaison and linkage between China and the rest of the world.”

The team would likely include epidemiological, laboratory and communications experts, but the matter was still being discussed by the two sides and it remained unclear if and when such a group would arrive, O’Leary said.

There could be additional infections, both among animals and humans, in other regions and authorities have stepped up measures to monitor cases of pneumonia with unexplained causes, said Liang Wannian, director of the Chinese health agency’s H7N9 flu prevention and control office.

Liang said Chinese experts also were in the early stages of researching a possible vaccine for the virus, though it might not be needed if the virus remains only sporadically reported and if it does not spread easily among people.

The H7N9 strain previously was known only to infect birds, and officials say they do not know why the virus is infecting humans now. The virus has been detected in live poultry in several food markets where human cases have been found, leading officials to think people are most likely contracting the virus through direct contact with infected fowl.

Authorities have halted live poultry trade in cities where cases have been reported, and slaughtered fowl in markets where the virus has been detected.

Further investigations are underway and, for now, there’s no evidence the virus is spreading easily between people. However, scientists are watching closely to see if the flu poses a substantial risk to public health or could potentially spark a global pandemic.

In 2003, China allowed WHO to send a five-member team to help investigate an outbreak of the fatal flu-like illness, SARS, after its own experts could not trace the source of the disease.

China’s response at the time was slow. The government stayed silent for months after the first cases of an unidentified disease were reported, a cover-up that contributed to the spread of the virus to many parts of China and to two dozen other countries, killing hundreds of people.

International observers say that over the past decade, China’s public health agencies have become increasingly forthcoming with information.

Bee venom may offer protection

A NEW research has revealed that ‘functional cure’ for Human Immuno-deficiency Virus (HIV)/Acquired Immune Deficiency Syndrome (AIDS) can be achieved for some patients diagnosed early.

Meanwhile, another research has found that a component of bee venom packaged in super-tiny blobs can knock out HIV.

Treating people with HIV rapidly after they have become infected with the virus that causes AIDS may be enough to achieve a ‘functional cure’ in a small proportion of patients, according to the research published in PLoS Pathogens.

According to the report of the research culled from DailMailOnline, the treatment, for now, is only effective in about one in ten people diagnosed early, but most people who are infected with HIV do not learn of their infection until the virus has fully taken hold.

Scientists in France followed 14 patients who were treated within ten weeks of becoming infected with the virus. They received treatment for three years before stopping taking the medication.

The scientists found that even when the patients had been off therapy for more than seven years, they still showed no signs of the virus bouncing back – normally the virus rebounds if treatment is stopped.

The research, published in the journal PLoS Pathogens, follows news earlier this month about a baby girl in Mississippi, United States (U.S.), being effectively cured of the HIV after receiving very early treatment.

Christine Rouzioux, a professor at Necker Hospital and University Paris Descartes, and a member of the initial team, which identified HIV 30 years ago, said the new results showed that the number of infected cells circulating in the blood of these patients, known as ‘post-treatment controllers’, kept falling even without treatment.

“Early treatment in these patients may have limited the establishment of viral reservoirs, the extent of viral mutations, and preserved immune responses. A combination of those may contribute to control infection in post-treatment controllers,” she said.

“The shrinking of viral reservoirs … closely matches the definition of ‘functional’ cure,” she added.

A functional cure describes when the virus is reduced to such low level that it is kept at bay even without continuing treatment. The virus, however, is still detectable in the body.

Researchers testing the delivery system in lab dishes, in a report published in Antiviral Therapy, noted that these nanoparticles attach to and destroy the virus without damaging cells, offering an early glimpse of a technology that might -with a lot more testing -prevent HIV infection in some people.

“This is definitely a novel approach,” says Antony Gomes, a physiologist at the University of Calcutta in India, who studies the medical use of venoms. “There are very few reports available on venom-based treatment against viruses. This type of research has the potential to proceed further for product development.”

Physician-researcher Joshua Hood of Washington University in St. Louis and his colleagues tested the toxin-carrying nanoparticles on HIV in the lab. The particles preferentially locked onto HIV and delivered their cargo: The venom component, a toxin called melittin, poked holes in HIV’s protective protein coat, leading to sharply reduced amounts of virus, the researchers report in the current issue of Antiviral Therapy.

They also tested it in healthy human cells obtained from vaginal walls. Although melittin is known to degrade cell membranes, these vaginal cells were largely unperturbed by the treatment because the nanoparticles holding the melittin come equipped with protective structures attached on their outsides. These act as bumpers to prevent the nanoparticles - and particularly the toxin they carry - from contacting the cell membrane. That allows the nanoparticle to bind to the much smaller virus using a specific lock-and-key structure that fits onto the virus’s protein shell.

Happy pi-day everyone!

A Man’s Journey From Nepal To Texas Triggers Global TB Scramble

We don’t know too much about a Nepalese man who’s in medical isolation in Texas while being treated for extensively drug-resistant tuberculosis, or XDR-TB, the most difficult-to-treat kind. Health authorities are keen to protect his privacy.

But we do know that he traveled through 13 countries — from South Asia to somewhere in the Persian Gulf to Latin America — before he entered the U.S. illegally from Mexico in late November. He traveled by plane, bus, boat, car and on foot.

And all the way he may have unwittingly put hundreds of other people at risk of getting the highly drug-resistant TB strain.

That possibility has triggered a far-reaching investigation by the U.S. and other health authorities to track down potentially exposed people around the world. “It’s a huge effort that’s ongoing,” Dr. Martin Cetron, who heads the division of global management and quarantine at the Centers for Disease Control and Prevention, tells Shots.

The case, first described by Betsy McKay at the The Wall Street Journal, provides a window on a problem that health officials say is sure to arise more and more often.

XDR-TB is a more dangerous part of a bigger problem with multi-drug-resistant tuberculosis, or MDR-TB.

“We estimate at any one time in the world there are about 630,000 cases of MDR-TB,” Dr. Dennis Falzon of the World Health Organization tells Shots, referring to multi-drug-resistant TB. MDR-TB isn’t vanquished by the two mainstay drugs isoniazid and rifampin and requires more complicated drug regimens.

In 2007, a young lawyer named Andrew Speaker became the best-known case of MDR-TB when he flew to Europe, potentially exposing other passengers.

XDR-TB is resistant not only to isoniazid and rifampin but also a class of drugs called fluoroquinolones and one or more potent injectable antibiotics. TB germs become drug-resistant when patients fail to complete a course of treatment. When a partly-resistant strain is treated with the wrong drugs, it can become extensively resistant.

There are about 60,000 people with XDR-TB strains like the Nepalese man who’s in isolation, Falzon says.

That means there are other people with XDR-TB traveling the world at any given time. Like the Nepalese man, until he got to the U.S., Falzon says, “many of these XDR cases aren’t even diagnosed.”

To give some idea of the public health challenge, such cases present, Dr. Kenneth Castro of the CDC’s division of TB elimination tells Shots that over 700 people were thought to be exposed to the Nepalese man while he was in the custody of the U.S. Border Patrol.

“Out of those, 60 percent or so are back in their country of citizenship which then leaves many others that are being sorted through to determine if (their exposure) was real or not,” Castro says.

But at least those potential contacts were known. Falzon says it’s almost impossible to trace people who may have had close contact with the man during his complicated itinerary.

“We cannot trace down a bus tour which happened within, let’s say, the space of a few weeks,” Falzon says. “And it’s very difficult to get details. The person (in detention) doesn’t speak English.”

The long-haul flight he took from a country on the Persian Gulf to Brazil, which exposed fellow travelers sitting within a couple of rows of his seat, occurred months ago. “We’re trying to track down the exact details of that flight and the persons who were exposed,” the WHO official says.

TB is spread through droplets in the air released by coughing or sneezing. It requires close and prolonged exposure, so a shorter flight, for instance, is not thought to pose a danger.

Castro says there’s no reason to think XDR-TB is more contagious than less-resistant or drug-susceptible strains. “The alarm bells have to do with the consequences of the disease,” he says — that is, the two-year, toxic, costly drug regimen necessary to cure the infection.

One big advantage these days, Castro says, is a lab test that can tell within two days whether a patient’s sputum contains TB bacilli with mutations that confer resistance to seven different drugs.

“This is a game-changer,” Castro says. The TB organism is notoriously slow-growing, so it used to take six weeks to culture it in laboratory dishes and test its susceptibility to different drugs. “The result is that some folks died before results of drug susceptibility tests came back,” he says.

The CDC has recorded 63 cases of XDR-TB from 1993 through 2011 (the most recent data available), more than half of them among foreign-born people.

When illegal immigrants with drug-resistant TB are isolated in ICE detention facilities, things get complicated. They cannot be deported until they’re no longer contagious, which can require months of complex treatment. Otherwise, they’d pose a risk to fellow travelers.

But Dr. Edward Zuroweste of the nonprofit group Migrants Clinicians Network says just because such patients are no longer contagious doesn’t mean they’re cured. This requires at least two more years of treatment — often back in a home country without specialists in treating drug-resistant TB or access to the proper drugs.

Zuroweste’s group has a contract with ICE to make sure deportees have appropriate treatment. It checks up on them regularly to see if they’re sticking with it. He says 84 percent complete treatment, and the rest either disappear or refuse further treatment.

He says the U.S. and other nations should expect to see growing numbers of these difficult cases. “There’s no way to ever isolate the U.S. from an airborne disease,” Zuroweste tells Shots. “The world is becoming much smaller and people travel a lot. So what we have to do is attack the disease, not the individual unfortunate enough to contract the disease.”

Viruses can acquire fully functional immune systems, according to new research that bolsters the controversial theory that viruses are living creatures.

Until now, scientists thought that viruses existed only as primitive particles of DNA or RNA, and therefore lacked the sophistication of an immune system.

The study, published in the journal Nature, is the first to show that a virus can indeed possess an immune system, not to mention other qualities commonly associated with complex life forms.

The belief that viruses are living creatures “stems from the fact that viruses have their own complex genome, they replicate to make more of themselves, and they are evolving,” co-author Andrew Camilli of the Tufts University School of Medicine told Discovery News.

The use of a complex immune system “doesn’t prove” that viruses are living beings, “but it does add to the argument,” he said.

Living organisms are typically defined as being capable of vital functions, such as the ability to grow and adapt to the environment over successive generations. Viruses are now on the fence between being considered a biological entity and an actual living creature.

Camilli and his colleagues focused their investigation on a viral predator of cholera bacteria. This type of virus is known as a bacteriophage (“phage” for short).

Lead author Kimberley Seed, a postdoctoral fellow in Camilli’s lab, was analyzing DNA sequences of phages taken from stool samples of Bangladesh cholera patients. She was surprised to find genes for a functional immune system previously only found in some types of bacteria.

To verify the discovery, she and her colleagues used phages both with and without the immune system to infect a new strain of cholera bacteria. Only the virus harboring the immune system readily killed the cholera bacteria.

Not only can some viruses have an immune system; some also can steal them from bacteria.

The scientists found that viruses can capture immunity genes from bacteria during a phase when “the viral genome is being replicated into dozens of copies within the infected host cell,” Camilli explained. The virus therefore steals an immune system from the bacteria. This benefits the phage virus.

NEWS: Giant Viruses Are Ancient Living Organisms

“The immune system allows the phage to target and destroy specific inhibitory genes of the host cell by literally cutting the target genes into pieces,” Seed told Discovery News. By disarming these genes, “the phage essentially disarms the host cell, and can then proceed with the infection and kill the host cell.”

While we tend to associate both viruses and bacteria with health threats, that is not always the case. In this instance, the virus winds up on the side of humans.

Camilli explained that “phages are killers of bacteria. If the species of bacteria they happen to kill is a human pathogen, then the phage is doing us a favor.”

The researchers hope that this activity could battle “superbugs,” which are bacteria with a resistance to most are all current antibiotics.

Mammals, including humans, possess immune systems that, unlike those of bacteria, are encoded on much larger pieces of DNA.

“It would be very difficult, if not impossible, for a virus to capture (such an immune system),” Camilli said.

“A second consideration is that the virus has to have a good use for the captured immune system in order to hang onto it,” he added. “In the case of a phage, we have shown that it can use the captured immune system to good effect. This may or may not be true for another type of immune system, should a virus be able to capture it.”

Sylvain Moineau, a professor in the Department of Biochemistry, Microbiology and Bioinformatics at Université Laval, is one of the world’s leading experts on bacteriophages. Moineau told Discovery News that the discovery of a phage with an immune system “is a remarkable finding. Phages always seem to find a way to impress us.”

Moineau and colleague Manuela Villion remind that phages are among the most abundant biological entities on the planet, outnumbering their bacterial hosts tenfold. Whether they and other viruses represent living organisms, however, is still up for debate.

Doctors in the US have made medical history by effectively curing a child born with HIV, the first time such a case has been documented.

The infant, who is now two and a half, needs no medication for HIV, has a normal life expectancy and is highly unlikely to be infectious to others, doctors believe.

Though medical staff and scientists are unclear why the treatment was effective, the surprise success has raised hopes that the therapy might ultimately help doctors eradicate the virus among newborns.

Doctors did not release the name or sex of the child to protect the patient’s identity, but said the infant was born, and lived, in Mississippi state. Details of the case were unveiled on Sunday at the Conference on Retroviruses and Opportunistic Infections in Atlanta.

Dr Hannah Gay, who cared for the child at the University of Mississippi medical centre, told the Guardian the case amounted to the first “functional cure” of an HIV-infected child. A patient is functionally cured of HIV when standard tests are negative for the virus, but it is likely that a tiny amount remains in their body.

“Now, after at least one year of taking no medicine, this child’s blood remains free of virus even on the most sensitive tests available,” Gay said.

“We expect that this baby has great chances for a long, healthy life. We are certainly hoping that this approach could lead to the same outcome in many other high-risk babies,” she added.

The number of babies born with HIV in developed countries has fallen dramatically with the advent of better drugs and prevention strategies. Typically, women with HIV are given antiretroviral drugs during pregnancy to minimise the amount of virus in their blood. Their newborns go on courses of drugs too, to reduce their risk of infection further. The strategy can stop around 98% of HIV transmission from mother to child.

In the UK and Ireland, around 1,200 children are living with HIV they picked up in the womb, during birth, or while being breastfed. If an infected mother’s placenta is healthy, the virus tends not to cross into the child earlier in pregnancy, but can in labour and delivery.

The problem is far more serious in developing countries. In sub-Saharan Africa, around 387,500 children aged 14 and under were receiving antiretroviral therapy in 2010. Many were born with the infection. Nearly 2 million more children of the same age in the region are in need of the drugs.

In the latest case, the mother was unaware she had HIV until after a standard test came back positive while she was in labour. “She was too near delivery to give even the dose of medicine that we routinely use in labour. So the baby’s risk of infection was significantly higher than we usually see,” said Gay.

Doctors began treating the baby 30 hours after birth. Unusually, they put the child on a course of three antiretroviral drugs, given as liquids through a syringe. The traditional treatment to try to prevent transmission after birth is a course of a single antiretroviral drug. The doctor opted for the more aggressive treatment because the mother had not received any during her pregnancy.

Several days later, blood drawn from the baby before treatment started showed the child was infected, probably shortly before birth. The doctors continued with the drugs and expected the child to take them for life.

However, within a month of starting therapy, the level of HIV in the baby’s blood had fallen so low that routine lab tests failed to detect it.

The mother and baby continued regular clinic visits to the clinic for the next year, but then began to miss appointments, and eventually stopped attending all together. The child had no medication from the age of 18 months, and did not see doctors again until it was nearly two years old.

“We did not see this child at all for a period of about five months,” Gay told the Guardian. “When they did return to care aged 23 months, I fully expected that the baby would have a high viral load.”

When the mother and child arrived back at the clinic, Gay ordered several HIV tests, and expected the virus to have returned to high levels. But she was stunned by the results. “All of the tests came back negative, very much to my surprise,” she said.

The case was so extraordinary, Dr Gay called a colleague, Katherine Luzuriaga, an immunologist at Massachusetts Medical School, who with another scientist, Deborah Persaud at Johns Hopkins Children’s Centre in Baltimore, had far more sensitive blood tests to hand. They checked the baby’s blood and found traces of HIV, but no viruses that were capable of multiplying.

The team believe the child was cured because the treatment was so potent and given swiftly after birth. The drugs stopped the virus from replicating in short-lived, active immune cells, but another effect was crucial. The drugs also blocked the infection of other, long-lived white blood cells, called CD4, which can harbour HIV for years. These CD4 cells behave like hideouts, and can replace HIV that is lost when active immune cells die.

The treatment would not work in older children or adults because the virus will have already infected their CD4 cells.

“Prompt antiviral therapy in newborns that begins within days of exposure may help infants clear the virus and achieve long-term remission without lifelong treatment by preventing such viral hideouts from forming in the first place,” said Dr Persaud. “Our next step is to find out if this is a highly unusual response to very early antiretroviral therapy or something we can actually replicate in other high-risk newborns.”

Children infected with HIV are given antiretroviral drugs with the intent to treat them for life, and Gay warned that anyone who takes the drugs must remain on them.

“It is far too early for anyone to try stopping effective therapy just to see if the virus comes back,” she said.

Until scientists better understand how they cured the child, Gay emphasised that prevention is the most reliable way to stop babies contracting the virus from infected mothers. “Prevention really is the best cure, and we already have proven strategies that can prevent 98% of newborn infections by identifying and treating HIV-positive women,” she said.

Genevieve Edwards, a spokesperson for the Terrence Higgins Trust HIV/Aids charity, said: “This is an interesting case, but I don’t think it has implications for the antenatal screening programme in the UK, because it already takes steps to ensure that 98% to 99% of babies born to HIV-positive mothers are born without HIV.”

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