H7N9 Double Whammy: Develops Drug Resistance, Remains Infectious
December 11, 2013

H7N9 Double Whammy: Develops Drug Resistance, Remains Infectious

Lawrence LeBlond for redOrbit.com - Your Universe Online

A deadly strain of avian bird flu that has been sickening people in China since last March has been offering health experts plenty of research material, with the most recent study showing that an H7N9 mutation has been found not to lose its ability to spread to mammals, despite developing resistance to drugs.

It is commonly known in medical science that seasonal flu strains often become less transmissible once they develop resistance to treatment drugs such as Roche’s Tamiflu. However, the H7N9 bird flu strain has been found to not follow this rule of thumb.

While this does not necessarily mean H7N9 will be more likely to become a human pandemic, the research team, led by Nicole Bouvier, a researcher with the Icahn School of Medicine at Mount Sinai’s Department of Microbiology and Division of Infectious Diseases, said it means doctors should use discretion in their reliance on antivirals to treat H7N9 cases. Also, they should consider using drugs other than Tamiflu whenever possible.

Tamiflu, and its generic counterpart oseltamivir, are common antiviral drugs for the treatment of flu infections. However, human cases of Tamiflu-resistant H7N9 were found swiftly following the outbreak earlier this year.

"It's important to emphasize that these H7N9 viruses seem to transmit fairly inefficiently overall," said Bouvier, whose study is published in the journal Nature Communications on Tuesday.

"But what was surprising about our study was that the drug-resistant virus was no less efficient than the drug-sensitive one. Usually what we see with influenza, is that resistance...also confers a fitness disadvantage on the virus," Bouvier told Reuters’ Kate Kelland in an interview.

For the study, Bouvier and colleagues at the Mount Sinai School of Medicine in NY analyzed a mutated strain of the H7N9 virus taken from a sample of an infected patient in China. The team examined the virus’ resistance to drugs, as well as it infectivity.

Their analysis revealed that this particular strain was not only highly resistant to Tamiflu, but that it also still had the ability to infect human cells in a lab dish. Furthermore, it was able to spread just as efficiently in lab animals as its non-mutated counterpart.

"This is unusual, as it is known that when seasonal influenza viruses gain resistance to drugs, it usually happens at a cost to the virus - the cost being a reduced ability to transmit between hosts and to grow within them," the researchers wrote.

The team also notes that because treating flu with antivirals often leads to drug resistance, in the case of this strain, a higher level of prudence is needed, since H7N9 has shown the ability to also remain highly infective once it develops resistance.

Experts have also noted that while there is no evidence of sustained human-to-human transmission of H7N9, recent studies have shown that the virus has the ability to jump between people and could potentially become a human pandemic.

In a study published Dec. 6, 2013 in the journal Science, researchers from The Scripps Research Institute (TSRI) found that the H7N9 strain that emerged in China earlier this year is poorly adapted for sustained transmission between humans. As such, they suggest that the current form of the virus is unlikely to cause a pandemic.

Ian A. Wilson, PhD, and James C. Paulson, PhD, both of TSRI, noted that most of the cases of infection were linked to exposure to infected poultry, but some cases may have been a result of limited human-to-human transmission.

For their study, the research team examined the three-dimensional structures of the hemagglutinin (HA) protein on the surface of the H7N9 virus and its interaction with the human influenza receptor – the molecule on the surface of human cells that HA binds to before entering the cell and causing infection.

Previous research had shown that compared to influenza viruses that are adapted to spread easily among birds, viruses adapted to humans generally have different amino acids at the HA site that recognize and bind to the human receptor.

Recent studies have shown that certain H7N9 viruses had acquired mutations that might make them more adapted to humans. However the TSRI team demonstrated that the HA in the avian H7N9 virus most closely resembles that of viruses that spread easily among birds, yet only attach to human receptors very weakly.

While it could potentially become more transmissible among humans, the H7N9 virus would need to undergo multiple mutations to do so, the team wrote.

For now, all scientists can do is keep a watchful eye for any sign that the virus may develop such potential.

Since the H7N9 outbreak first came to light in March, the virus has sickened more than 140 people and has killed at least 45. On Dec 10, 2013, the World Health Organization reported that it had been informed of four new laboratory-confirmed cases between Nov 28 and Dec 6, 2013.