PRO/AH/EDR> Avian influenza, human (114): China (H7N9) receptor properties
Date: Tue 10 Sep 2013
Source: News Medical [edited]
A new study has found that the novel avian-origin H7N9 influenza A virus, which has recently emerged in humans, attaches moderately or abundantly to the epithelium of both the upper and lower respiratory tracts. This pattern has not been observed before for other avian influenza A viruses. The report, published in the October 2013 issue of The American Journal of Pathology, suggests that the emerging H7N9 virus has the potential to cause a pandemic, since it may transmit efficiently in humans and cause severe pneumonia.
The 1st report of infections of humans with the influenza A virus of the subtype H7N9 surfaced in March 2013. Three patients from eastern China developed severe pneumonia and acute respiratory distress syndrome and died as a result. By 30 May 2013, the H7N9 infection was confirmed in 132 patients from China and Taiwan, 37 of whom died, according to the World Health Organization. Infected poultry were thought to be the source of the virus.
In the current study, investigators focused on the virus' pattern of attachment in order to assess its potential transmissibility and virulence. "Abundant virus attachment to the human upper respiratory tract correlates with efficient transmissibility among humans," explains Thijs Kuiken, DVM, PhD of the Department of Viroscience at Erasmus University Medical Centre in Rotterdam, The Netherlands. "Virus attachment to Clara cells in the bronchioles and pneumocytes and macrophages in the alveoli correlates with high virulence."
Using virus histochemical analysis, the investigators looked at the pattern of attachment of 2 genetically engineered emerging H7 viruses (containing the hemagglutinin (HA) of either influenza virus A/Shanghai/1/13 or A/Anhui/1/13) to fixed human respiratory tract tissues and compared the findings to attachment patterns seen with human influenza viruses with high transmissibility but low virulence (seasonal H3N2 and pandemic H1N1) and highly pathogenic avian influenza (HPAI) viruses with low transmissibility and high virulence (H5N1 and H7N7). They found that like other avian influenza viruses, the H7N9 viruses attached more strongly to lower parts of the human respiratory tract than to upper parts. However, compared to other avian influenza viruses, the attachment to epithelial cells by H7N9 in the bronchioles and alveoli of the lung was more abundant, and the viruses attached to a broader range of cell types. "These characteristics fit with increased virulence of these emerging avian H7 viruses compared to that of human influenza viruses," says Dr. Kuiken.
A 3rd notable finding was a more concentrated attachment of H7N9 viruses in ciliated cells of the nasal concha, trachea, and bronchi, suggesting the potential for efficient transmission among humans. "However, the fact that the emerging H7N9 virus has caused infection mainly in individual human cases suggests that it has not acquired all the necessary properties for efficient transmission among humans," notes Dr. Kuiken. "Our results indicate that based just on the pattern of virus attachment, the H7N9 currently emerging in China has the potential both to cause severe pulmonary disease and to be efficiently transmitted among humans," says Dr. Kuiken. He emphasizes that attachment is only the 1st step in the replication cycle of influenza virus in its host cell, and that other steps, as well as the host response, need to be taken into account to fully understand the potential of these emerging H7 viruses to cause an influenza pandemic.
Date: 5 Sep 2013
Source: Science DOI: 10.1126/science.1242917 [edited]
Structures and Receptor Binding of Hemagglutinins from Human-Infecting H7N9 Influenza Viruses. (By Y Yi Shi and 20 other contributors).
An avian-origin human-infecting influenza (H7N9) virus has recently been identified in China. Here, we have evaluated the viral hemagglutinin (HA) receptor binding properties from 2 human H7N9 isolates, A/Shanghai/1/2013 (SH-H7N9) (containing the avian-signature Q226) and A/Anhui/1/2013 (AH-H7N9) (containing the mammalian-signature L226). We found that SH-H7N9 HA preferentially binds the avian receptor analog, whereas the AH-H7N9 HA binds both avian and human receptor analogs. Furthermore, an AH-H7N9 mutant HA (L226Q) has dual receptor binding property, indicating that other amino acid substitutions contribute to the receptor binding switch. The structures of SH-H7N9 HA, AH-H7N9 HA, and its mutant in complex with either avian or human receptor analogs show how the AH-H7N9 can bind human receptors yet also retain the avian receptor binding property.
[In the 1st report above, the authors believe that, based just on the pattern of virus attachment, the H7N9 currently emerging in China has the potential both to cause severe pulmonary disease and to be efficiently transmitted among humans and cause severe pneumonia. However, the fact that the emerging H7N9 virus has caused infection mainly in individual human cases suggests that it has not acquired all the necessary properties for efficient transmission among humans.
The authors of the 2nd report above conclude that "loss of affinity for the avian receptor may be an important factor for development of efficient human-to-human transmission; however, to date, limited human-to-human transmission has been observed for H7N9 virus, which might be a result of retention of high affinity for the avian receptor." The authors of the Science report showed that, "in contrast to the H5N1 HA, the Q226L substitution is not solely responsible for the avian-to-human receptor binding switch for H7 HA." They conclude that: "We believe that surveillance of H7N9 virus isolates for detection of the new amino acid substitutions is essential for the future implementation of control strategies." - Mod.CP
A HealthMap/ProMED-mail map can be accessed at: http://healthmap.org/r/1zaU.]