H7N9 avian influenza has pandemic potential

The emerging H7N9 avian influenza A virus, which has claimed the lives of at least 40 people, carries traits that make it easily adaptable to humans, making this virus a candidate to cause a pandemic, according to several research papers.

Yoshihiro Kawaoka, PhD, of the University of Wisconsin-Madison, and researchers from the University of Tokyo published a paper recently in Nature that analyzed two of the first human isolates of the virus from patients in China, and their data suggest that H7N9 viruses have the potential to become a worldwide threat to human health.

“H7N9 viruses have several features typically associated with human influenza viruses and therefore possess pandemic potential and need to be monitored closely,” Kawaoka said in a prepared statement on the paper published as a letter in the journal this month.

In a related commentary also published this month, scientists at the National Institute of Allergy and Infectious Diseases (NIAID) noted that although avian H7 viruses have caused numerous influenza outbreaks among poultry in Europe and North America, none has yet to evolve into a strain that has widely infected humans or caused a pandemic.

However, the NIAID researchers warned that some of the H7 viruses — including the H7N9 virus — have stably adapted to infect mammals such as horses, suggesting that these viruses might become adapted to and transmissible among other mammals, including humans.

In the case of the H7N9 virus, many of its genes are shared with the H9N2 influenza virus subtype, which has also infected humans. This genetic relatedness may predispose it to more easily adapt to humans than other H7 viruses, according to the NIAID researchers.

Amino acid changes

Kawaoka and colleagues said that the ability of the H7N9 virus to infect and replicate in human cells may be possible with only a few amino acid changes in the genetic sequence of the virus.

In monkeys, the H7N9 virus was shown to efficiently infect cells in both the upper and lower respiratory tract. Conventional human influenza viruses are typically restricted to the upper airway of infected nonhuman primates.

“If H7N9 viruses acquire the ability to transmit efficiently from person to person, a worldwide outbreak is almost certain since humans lack protective immune responses to these types of viruses,” Kawaoka said.

Figure 1. Infectious particles of the avian H7N9 virus emerge from a cell. The virus, according to a new report in the journal Nature, has qualities that make it a potential global human health threat.

Source: Takeshi Noda, University of Tokyo

Transmission studies conducted by Kawaoka’s group in ferrets — animals that, like humans, infect one another through coughing and sneezing and that are a standard model for studies of influenza in mammals — showed that one of the H7N9 strains isolated from humans can transmit via respiratory droplets, though not as efficiently as human influenza viruses.

The limited aerosol transmission observed in ferrets adds to concerns about the potential threat as avian influenza viruses typically lack that ability, Kawaoka and colleagues noted.

Role of antivirals

The positive news conveyed in Kawaoka’s report is that most of the H7N9 strains tested were somewhat sensitive to antiviral drugs effective against seasonal influenza virus, which seemed to be the case in at least one of the World Health Organization’s most recently-reported patients with the illness.

According to a press release from WHO, the National Health and Family Planning Commission in China notified WHO officials of a 15-year-old boy reported from Jiangsu who became ill on April 25 and was hospitalized the next day. He recovered and was discharged on May 2. The results of molecular diagnostics were positive for influenza A/H3N2 seasonal influenza virus and H7N9 avian influenza virus.

In the WHO release, officials noted that so far, there is no evidence of sustained human-to-human transmission, but they said it is expected that there will be additional human infections.

Research needed

The possibility that more cases of H7N9 are expected and the possibility that this virus may adapt to easily infect humans highlights a need for more research on how avian influenza strains adapt to mammals, especially humans, and better integration of influenza research between human and veterinary public health specialists, according to the NIAID researchers.

Kawaoka and colleagues said that this type of research is going to be all the more important, since H7N9 virus does not kill poultry, which promises to make surveillance much more difficult.

“We cannot simply watch out for sick or dead birds. Rather, tests have to be performed to determine whether or not a bird is infected. Considering the vast number of poultry, this is a daunting task.”

Further research is needed to support vaccine development, to assess the risks, and to better understand why the H7N9 viruses infect humans so efficiently, Kawaoka and colleagues said.

For more information:

Kawaoka Y. Nature. 2013; doi:10.1038/nature12392.

Morens DM. mBio 2013; doi: 10.1128/mBio.00445-13.

Disclosure: Kawaoka reports no relevant financial disclosures.