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Potential Pandemic of H7N9 Avian Influenza A Virus in Human.

ABSTRACT: Since 2013, the H7N9 avian influenza A virus (AIV) has caused human infections and to the extent of now surpassing H5N1. This raises an alarm about the potential of H7N9 to become a pandemic problem. Our compilation of the amino acid changes required for AIVs to cross the species-barrier discovers 58 that have very high proportions in both the human- and avian-isolated H7N9 viruses. These changes correspond with sporadic human infections that continue to occur in regions of avian infections. Among the six internal viral genes, amino acid changes do not differ significantly between H9N2 and H7N9, except for V100A in PA, and K526R, D627K, and D701N in PB2. H9N2 AIVs provide internal genes to H7N9. Most of the amino acid changes in H7N9 appear to come directly from H9N2. Seventeen amino acid substitutions appear to have fixed quickly by the 5th wave. Among these, six amino acid sites in HA1 are receptor binding sites, and PB2-A588V was shown to promote the adaptation of AIVs to mammals. The accelerated fixation of mutations may promote the adaptation of H7N9 to human, but need further functional evidence. Although H7N9 AIVs still cannot efficiently transmit between humans, they have the genetic makeup associated with human infections. These viruses must be controlled in poultry to remove the threat of it becoming a human pandemic event.

SUBMITTER: Pu Z

PROVIDER: S-EPMC6265602 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Potential Pandemic of H7N9 Avian Influenza A Virus in Human.

Pu Zhiqing Z Xiang Dan D Li Xiaobing X Luo Tingting T Shen Xuejuan X Murphy Robert W RW Liao Ming M Shen Yongyi Y

Frontiers in cellular and infection microbiology 20181123

Since 2013, the H7N9 avian influenza A virus (AIV) has caused human infections and to the extent of now surpassing H5N1. This raises an alarm about the potential of H7N9 to become a pandemic problem. Our compilation of the amino acid changes required for AIVs to cross the species-barrier discovers 58 that have very high proportions in both the human- and avian-isolated H7N9 viruses. These changes correspond with sporadic human infections that continue to occur in regions of avian infections. Amo ...[more]

PMID: 30533399

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Project description:H7N9 avian influenza viruses (AIVs) continue to evolve and remain a huge threat to human health and the poultry industry. Previously, serially passaging the H7N9 A/Anhui/1/2013 virus in the presence of homologous ferret antiserum resulted in immune escape viruses containing amino acid substitutions alanine to threonine at residues 125 (A125T) and 151 (A151T) and leucine to glutamine at residue 217 (L217Q) in the hemagglutinin (HA) protein. These HA mutations have also been found in field isolates in 2019. To investigate the potential threat of serum escape mutant viruses to humans and poultry, the impact of these HA substitutions, either individually or in combination, on receptor binding, pH of fusion, thermal stability, and virus replication were investigated. Our results showed the serum escape mutant formed large plaques in Madin-Darby canine kidney (MDCK) cells and grew robustly in vitro and in ovo They had a lower pH of fusion and increased thermal stability. Of note, the serum escape mutant completely lost the ability to bind to human-like receptor analogues. Further analysis revealed that N-linked glycosylation, as a result of A125T or A151T substitutions in HA, resulted in reduced receptor-binding avidity toward both human and avian-like receptor analogues, and the A125T+A151T mutations completely abolished human-like receptor binding. The L217Q mutation enhanced the H7N9 acid and thermal stability while the A151T mutation dramatically decreased H7N9 HA thermal stability. To conclude, H7N9 AIVs that contain A125T+A151T+L217Q mutations in the HA protein may pose a reduced pandemic risk but remain a heightened threat for poultry.IMPORTANCE Avian influenza H7N9 viruses have been causing disease outbreaks in poultry and humans. We previously determined that propagation of H7N9 virus in virus-specific antiserum gives rise to mutant viruses carrying mutations A125T+A151T+L217Q in their hemagglutinin protein, enabling the virus to overcome vaccine-induced immunity. As predicted, these immune escape mutations were also observed in the field viruses that likely emerged in the immunized or naturally exposed birds. This study demonstrates that the immune escape mutants also (i) gained greater replication ability in cultured cells and in chicken embryos as well as (ii) increased acid and thermal stability but (iii) lost preferences for binding to human-type receptor while maintaining binding for the avian-like receptor. Therefore, they potentially pose reduced pandemic risk. However, the emergent virus variants containing the indicated mutations remain a significant risk to poultry due to antigenic drift and improved fitness for poultry.

Project description:BackgroundThe first identified cases of avian influenza A(H7N9) virus infection in humans occurred in China during February and March 2013. We analyzed data obtained from field investigations to describe the epidemiologic characteristics of H7N9 cases in China identified as of December 1, 2013.MethodsField investigations were conducted for each confirmed case of H7N9 virus infection. A patient was considered to have a confirmed case if the presence of the H7N9 virus was verified by means of real-time reverse-transcriptase-polymerase-chain-reaction assay (RT-PCR), viral isolation, or serologic testing. Information on demographic characteristics, exposure history, and illness timelines was obtained from patients with confirmed cases. Close contacts were monitored for 7 days for symptoms of illness. Throat swabs were obtained from contacts in whom symptoms developed and were tested for the presence of the H7N9 virus by means of real-time RT-PCR.ResultsAmong 139 persons with confirmed H7N9 virus infection, the median age was 61 years (range, 2 to 91), 71% were male, and 73% were urban residents. Confirmed cases occurred in 12 areas of China. Nine persons were poultry workers, and of 131 persons with available data, 82% had a history of exposure to live animals, including chickens (82%). A total of 137 persons (99%) were hospitalized, 125 (90%) had pneumonia or respiratory failure, and 65 of 103 with available data (63%) were admitted to an intensive care unit. A total of 47 persons (34%) died in the hospital after a median duration of illness of 21 days, 88 were discharged from the hospital, and 2 remain hospitalized in critical condition; 2 patients were not admitted to a hospital. In four family clusters, human-to-human transmission of H7N9 virus could not be ruled out. Excluding secondary cases in clusters, 2675 close contacts of case patients completed the monitoring period; respiratory symptoms developed in 28 of them (1%); all tested negative for H7N9 virus.ConclusionsMost persons with confirmed H7N9 virus infection had severe lower respiratory tract illness, were epidemiologically unrelated, and had a history of recent exposure to poultry. However, limited, nonsustained human-to-human H7N9 virus transmission could not be ruled out in four families.

Project description:BackgroundCharacterisation of the severity profile of human infections with influenza viruses of animal origin is a part of pandemic risk assessment, and an important part of the assessment of disease epidemiology. Our objective was to assess the clinical severity of human infections with avian influenza A H7N9 virus, which emerged in China in early 2013.MethodsWe obtained information about laboratory-confirmed cases of avian influenza A H7N9 virus infection reported as of May 28, 2013, from an integrated database built by the Chinese Center for Disease Control and Prevention. We estimated the risk of fatality, mechanical ventilation, and admission to the intensive care unit for patients who required hospital admission for medical reasons. We also used information about laboratory-confirmed cases detected through sentinel influenza-like illness surveillance to estimate the symptomatic case fatality risk.FindingsOf 123 patients with laboratory-confirmed avian influenza A H7N9 virus infection who were admitted to hospital, 37 (30%) had died and 69 (56%) had recovered by May 28, 2013. After we accounted for incomplete data for 17 patients who were still in hospital, we estimated the fatality risk for all ages to be 36% (95% CI 26-45) on admission to hospital. Risks of mechanical ventilation or fatality (69%, 95% CI 60-77) and of admission to an intensive care unit, mechanical ventilation, or fatality (83%, 76-90) were high. With assumptions about coverage of the sentinel surveillance network and health-care-seeking behaviour for patients with influenza-like illness associated with influenza A H7N9 virus infection, and pro-rata extrapolation, we estimated that the symptomatic case fatality risk could be between 160 (63-460) and 2800 (1000-9400) per 100,000 symptomatic cases.InterpretationHuman infections with avian influenza A H7N9 virus seem to be less serious than has been previously reported. Many mild cases might already have occurred. Continued vigilance and sustained intensive control efforts are needed to minimise the risk of human infection.FundingChinese Ministry of Science and Technology; Research Fund for the Control of Infectious Disease; Hong Kong University Grants Committee; China-US Collaborative Program on Emerging and Re-emerging Infectious Diseases; Harvard Center for Communicable Disease Dynamics; US National Institute of Allergy and Infectious Disease; and the US National Institutes of Health.

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Potential Pandemic of H7N9 Avian Influenza A Virus in Human.

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Potential Pandemic of H7N9 Avian Influenza A Virus in Human.

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