H7N9 Virus is Both Deadly and Infectious in Animals
For the first time, Kawaoka says, his group has identified an influenza virus strain that is both transmissible between ferrets (the very best animal model proxy for individual flu infections) and deadly, both at the animal originally infected and in otherwise healthy ferrets in close contact with these infected animals. It has become a bit more easy recently to detect when poultry are infected with H7N9 allowing people to restrict their exposure. That is because the virus has started to kill birds from China, also. But unlike in the U.S., where farmers cull their flocks to limit the spread of infectious illness, China is based on vaccines.
This worries Kawaoka, given the virus was demonstrated to grow. "We can't do the experiments to learn why" Kawaoka says. "We really have to understand why H7N9 is deadly and transmissible, and what's different in this one resistant H7N9. If we understood that, because there are numerous viruses circulating, we can narrow down efforts to people who are deadly and transmissible."
To test whether the virus had been transmissible between mammals, the researchers set up experiments where ferrets were housed in individual cages separated by a barrier which allowed respiratory droplets to pass to another. While the other was put into the crate 21, in each pair, one ferret was deliberately infected with the virus. "Without additional mutations, the virus spread and killed ferrets," says Kawaoka, noting that further alterations to the virus may not be necessary to make it a potential public health threat, although human-to-human transmission has so far remained limited.
He recently released a comment in the Proceedings of the National Academy of Sciences, co-authored with two coworkers that are also specialists in flu, where they describe the challenges this moratorium generates for understanding the capacity of viruses such as H7N9 to become pandemic. "That is the first instance of a highly pathogenic avian virus that communicates between ferrets and kills them," Kawaoka says. "That is bad for public health." Each of those three virus types were transmitted from infected ferrets to the animals that were previously uninfected.
Two of three ferrets infected with the strain of H7N9 -- that the strain now circulating in China -- died, as did the animals to which they passed the virus. "I really don't want to cause alarm," Kawaoka says, but "it is only a matter of time until the immune virus acquires a mutation which allows it to grow well, (rendering it) more likely to be deadly at the same time it is resistant." Influenza viruses are well known for their propensity to accommodate.
With every new infection of a host, little changes take place within the genomes of influenza viruses. Sometimes these mutations happen in key regions and lead to significant alterations to the virus, which makes it capable of getting immune to the drugs typically utilized to deal with them, which makes hosts ill, causing illness, and infecting new hosts.
It stayed silent, passing infecting, unknown from chicken to chicken and, sometimes people that came into contact with the birds. Everybody in the influenza field knew it was only a matter of time before the virus became sterile in chickens, which would be to say that it became effective at causing illness, but Kawaoka says it required. It was initially hard to discover because, unlike another flu viruses such as H5N2 -- which is highly lethal in chickens and caused significant outbreaks on poultry farms across the U.S. and elsewhere in 2015 -- H7N9 was not killing the chickens it infected.
The H7N9 virus is very likely to continue to mutate because it infects humans, leading to adaptations that enhance the viruses' pathogenicity or ability Kawaoka adds. In other words, nature is doing its own experiments, together with serious consequences.
The group confirmed the drug-resistant H7N9 failed to respond to oseltamivir, the agent in Tamiflu. It did react to another drug called a protease inhibitor, but Kawaoka says it's a medication currently approved only in Japan and only for use in circumstances that are pandemic. The team found that every virus infects and causes sickness, in several animal models for influenza -- ferrets, mice and macaques, to varying degrees.
In early 2017, professor of pathobiological sciences at the University at Wisconsin-Madison School of Veterinary Medicine, Yoshihiro Kawaoka, received a sample of H7N9 virus isolated. He and his research team began work understand and to describe it. The first of these results are published today (Oct. 19, 2017) at Mobile Host & Microbe. However, Kawaoka and his team are currently unable to better understand what mutations may enable this transition, at least in the United States, where a moratorium on function that may cause a pathogen to undertake a new function not currently known in character has been in place for many decades.
Kawaoka and his group detected this within the sample isolated from the deceased patient, who had been treated with the flu drug Tamiflu. Utilizing a method to read the genetic identity of the virus population who had infected the patient, Kawaoka's group discovered the virus had begun to mutate: The sample comprised a population of virus which was sensitive to Tamiflu. In 2013, a flu virus that had never before been detected began moving among poultry in China.
It caused waves of infection and in 2016, the amount of individuals to become ill from the H7N9 virus started to rise. As of July 2017, nearly 1,600 people had tested positive. Almost 40 percent of those infected had died. So the team created two viruses almost identical to those isolated from the patient, one and the other bearing the mutation that conferred resistance. Comparing this to a variant of the virus that many others and Kawaoka had previously researched, the research team assessed every virus grows in cancerous cells, where most flu viruses take up residence within the body.
They discovered that every grew although the other two were not less powerful than the resistant strain. "consequences from (gain-of-function) studies would almost certainly assist in understanding the pandemic potential of flu viruses and create general health benefits, such as the prioritization and development of pre-pandemic vaccines and antiviral drugs," the authors write. Basic (gain-of-function) study on transmissibility, host-range restriction, drug resistance, immunogenicity, pathogenicity, and replicative capability would also benefit global public health."
