A study published this month in Nature by CDC researchers presents findings from animal studies conducted by CDC to better understand the transmissibility and disease characteristics of influenza A (H7N9) viruses isolated in China in late March. Understanding the properties of H7N9 viruses that contribute to human disease and the capacity of these viruses to spread between people is a critical component of the public health response to this emerging disease threat.
The study’s key findings indicate that H7N9 viruses are capable of causing infection in a direct contact animal model, but the viruses would need to undergo additional adaptation to spread more easily by droplets or through the air. Person to person transmission, especially by respiratory droplet transmission (such as through coughs and sneezes) is a necessary precondition for the virus to become capable of causing a pandemic.
These findings support the conclusions drawn from China’s investigations of human H7N9 cases so far. China has found no clear evidence of sustained human-to-human spread of the H7N9 virus. Human cases of H7N9 virus infection in China reported have been primarily associated with exposure to infected poultry. Currently no human cases of H7N9 virus infection have been reported in the United States.
The paper describes the results of multiple studies conducted on two H7N9 viruses obtained from fatal human H7N9 cases from China. The studies were conducted in ferrets, mice and human epithelial cells. Ferrets are considered the best small mammal for studying flu virus infection and are commonly used as a tool for the risk assessment of emerging flu viruses that may pose a risk to public health.
The ferret studies revealed that the H7N9 viruses spread readily among ferrets placed in the same cage. However, the viruses were less capable of respiratory droplet transmission, which the researchers tested by placing infected ferrets in cages adjacent to cages housing naive ferrets. Compared to a human seasonal flu virus from last season, the H7N9 viruses were considerably less capable of transmitting by the respiratory route.
Other study findings indicated that the H7N9 virus did not cause severe disease in the ferrets and did not spread systemically to the spleen, kidney, liver, or intestinal tract. The lack of systemic spread by H7N9 is different from H5N1 (another avian influenza virus that can cause severe disease in humans). Systemic spread is considered an indicator of severe disease.
In addition to ferrets, CDC researchers also studied the H7N9 virus in mice. Compared with ferrets, the virus caused more lethal illness in the mice, and the virus was more capable of replicating in the lungs of mice compared with other avian and human seasonal viruses tested in the study. Also notable, the H7N9 virus was able to easily infect mice, whereas human seasonal flu viruses typically require prior host adaptation to be able to efficiently infect mice.
The mouse studies also revealed that H7N9 virus can pass through the eyes to infect the respiratory tract. As a result, the eyes represent a possible portal of entry for the H7N9 virus. This finding supports CDC’s existing flu recommendations to avoid touching the eyes, nose or mouth to help prevent spread of germs. It also supports the recommendation for health care providers to wear eye protection when caring for patients with confirmed or suspected H7N9 infection.
The remaining study findings analyzed the H7N9 virus’s ability to replicate in cells derived from human epithelial cells. Epithelial cells are found in the human respiratory tract and are the primary site where flu viruses replicate in humans. CDC researchers found that the H7N9 virus demonstrated a 20- to 400-fold increase in replication at the two-day mark when compared with a human seasonal flu virus and two other avian flu viruses genetically related to the H7N9 virus. Compared with a human seasonal H3N2 virus, the H7N9 virus exhibited an 80,000-fold increase in replication at 24 hours.
The studies in mice and ferrets corroborated this finding, as considerably more H7N9 virus was produced and detected in the respiratory tracts of ferrets and mice compared with the amount of virus produced by seasonal flu virus infection. This suggests the H7N9 viruses have the capacity to reproduce quickly and produce a large amount of virus within the cells of mammals and human airway cells. However, the viruses’ ability to replicate was determined to be better suited to the higher temperatures found in the lower airways (lungs) versus the lower temperatures found in the upper airways of mammals.
The study, entitled “Pathogenesis and transmission of A (H7N9) avian influenza virus in ferrets and mice” is available for online viewing via Nature’s website.