Chinese scientists reported today that the first human infection with an H10N8 avian influenza virus involved a new strain that carries genes from H9N2 viruses and has a mutation associated with adaptation to mammals.

Writing in The Lancet, the scientists detailed the results of their genomic analysis of the virus, which was isolated from a 73-year-old Chinese woman who died Dec 6. Her illness was the first known human case involving that strain.

A second human case in China was reported by the country's government news agency on Jan 27. "The pandemic potential of this novel virus should not be underestimated," the Lancet authors warn.

The study says the genes for all six of the virus's internal proteins were derived from H9N2 viruses, which circulate in poultry and occasionally infect humans in China, usually causing a mild illness.

The authors say H9N2 viruses also provided the internal protein genes for the H7N9 virus, which has caused scores of deaths in China since last spring, and the H5N1 virus, which has killed more than 380 people since 2003.

A rapidly fatal illness

The woman who had the first H10N8 infection lived in Nanchang, the capital of Jiangxi province (also the home of the second case-patient), and had hypertension, coronary heart disease, and myasthenia gravis, the report says. She fell ill with a cough on Nov 27 and became feverish 2 days later.

On Nov 30 she was hospitalized with fever and severe pneumonia. Despite antibiotic and antiviral treatment, mechanical ventilation, and other measures, she died 9 days after her first symptoms.

Using polymerase chain reaction and sequencing, the authors found that tracheal samples from the patient were positive for H10N8 and negative for seasonal flu viruses, H5N1, H7N9, and H9N2. They isolated the virus and dubbed it A/Jiangxi-Donghu/346/2013(H10N8), or JX346 for short.

An epidemiologic investigation revealed that the patient had visited a live-poultry market 4 days before she got sick and had bought a chicken but did not handle it, the report says. She had no other contact with live poultry and no contact with sick people in the 2 weeks before her illness, nor had she traveled recently. The virus was not found in samples from the poultry market.

Investigators identified 17 contacts of the patient, including 11 healthcare workers, 5 family members, and 1 caregiver, none of whom had any signs of flu-like illness in the 2 weeks after their exposures. Throat swabs from the healthcare workers tested negative for flu viruses, and serologic tests on the relatives were also negative.

Genetic findings

The authors' genomic analysis of the virus showed that its hemagglutinin (H) protein was most closely related to that of a 2012 H10N3 duck isolate from Hunan province and that the neuraminidase (N) protein was most closely related to that of an H10N8 virus from a mallard in Korea.

All six of JX346's internal genes were closely related to those of H9N2 poultry viruses currently circulating in China, the authors found. But the internal genes were significantly different from those of previously reported H10 and N8 subtype viruses and were in different subclades from those of known H7N9 viruses.

Only two H10N8 viruses have been reported previously in China, one from a lake and the other from a poultry market, the report notes.

"H9N2 virus provided the internal genes not only for the H10N8 virus, but also for H7N9 and H5N1 viruses," the report says. "This relation should be studied further to understand the mechanism of how the internal genes of H9N2 virus transfer to viruses that infect people, and how the avian influenza virus transfers between species."

The authors say the findings suggest that JX346 might have originated from multiple reassortments between different avian flu viruses.

Senior author Yuelong Shu, PhD, of the Chinese Center for Disease Control and Prevention commented in a Lancet press release, "The H10 and H8 gene segments might have derived from different wild bird influenza viruses [that] reassorted to give rise to a hypothetical H10N8 virus in wild birds, which infected poultry and then reassorted with H9N2 viruses in poultry to give rise to the novel reassortant JX346 (H10N8) virus."

In other observations, the researchers say the patient's chronic medical conditions could have played a role in her death. But they found that the novel virus was "overwhelmingly dominant" in her tracheal specimens, which indicates that it was involved in her demise.

In addition, they found a mixture of glutamic acid and lysine at residue 627 in the virus's PB2 protein, a mutation that is associated with adaptation to, and can increase virulence in, mammals.

Further, the authors report that the novel virus preferentially binds avian-like alpha2,3-linked sialic acid receptors, which are "dominant in human lung tissue," suggesting a potential for the kind of lung damage found in human H5N1 infections.

The scientists observe that no poultry outbreak of H10N8 has been reported and that the virus's apparent low pathogenicity in poultry could help it circulate undetected, as is true of H7N9.

They conclude that the first human infection with H10N8 "further increases the importance of surveillance for pandemic preparedness and response."

Chen H, Yuan H, Gao R, et al. Clinical and epidemiological characteristics of a fatal case of avian influenza A H10N8 virus infection: a descriptive study. Lancet 2014 (published online Feb 4) [Abstract]