An Update on the H7N9 Strain of the Influenza A Virus

2013 ◽  
Vol 2 (3) ◽  
pp. 59-66
Author(s):  
Dimitrios Vlachakis ◽  
Argiro Karozou ◽  
Spyridon Champeris Tsaniras ◽  
Sophia Kossida
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
World Wide ◽  
Current Knowledge ◽  
H7n9 Virus ◽  
Pandemic Threat ◽  
H7n9 Influenza ◽  
Pharmacological Target ◽  
Informed Opinion ◽  
Public Concerns

Currently, humanity lives in the verge of a world-wide epidemic of the H7N9 influenza A virus. This strain has turned out to be very virulent for humans and there have been many reported casualties already in several places around the globe. Concordantly, not much is known for the H7N9 strain. Herein, the authors intend to establish a modest database of current knowledge and informed opinion in different key areas of the H7N9 virus. The source of the virus, its infection routes and mutations remain unclear. Results of several recent studies will be further analyzed including clinical, virological and histopathological manifestations of H7N9, diagnosis modes and viral transmissibility. Treatment, vaccination and public concerns about a pandemic threat will be discussed as well. The present work is expected to act as an updated world reference for the H7N9 influenza A strain. Moreover, modes for tackling H7N9 will be proposed, focusing on RNA polymerase for further investigation as a potential pharmacological target. Hence, invaluable conclusions may be drawn that will lead to insights in the fight against the most recent and rather lethal H7N9 strain.

scholarly journals Assessment of the Internal Genes of Influenza A (H7N9) Virus Contributing to High Pathogenicity in Mice

2014 ◽  
Vol 89 (1) ◽  
pp. 2-13 ◽  
Author(s):  
Yuhai Bi ◽  
Qing Xie ◽  
Shuang Zhang ◽  
Yun Li ◽  
Haixia Xiao ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Virulence Genes ◽  
H9n2 Virus ◽  
H7n9 Virus ◽  
High Pathogenicity ◽  
H7n9 Influenza ◽  
High Infectivity

ABSTRACTThe recently identified H7N9 influenza A virus has caused severe economic losses and worldwide public concern. Genetic analysis indicates that its six internal genes all originated from H9N2 viruses. However, the H7N9 virus is more highly pathogenic in humans than H9N2, which suggests that the internal genes of H7N9 have mutated. To analyze which H7N9 virus internal genes contribute to its high pathogenicity, a series of reassortants was generated by reverse genetics, with each virus containing a single internal gene of the typical A/Anhui/1/2013 (H7N9) (AH-H7N9) virus in the genetic background of the A/chicken/Shandong/lx1023/2007 (H9N2) virus. The replication ability, polymerase activity, and pathogenicity of these viruses were then evaluatedin vitroandin vivo. These recombinants displayed high genetic compatibility, and the H7N9-derived PB2, M, and NP genes were identified as the virulence genes for the reassortants in mice. Further investigation confirmed that the PB2 K627 residue is critical for the high pathogenicity of the H7N9 virus and the reassortant containing the H7N9-derived PB2 segment (H9N2-AH/PB2). Notably, the H7N9-derived PB2 gene displayed greater compatibility with the H9N2 genome than that of H7N9, endowing the H9N2-AH/PB2 reassortant with greater viability and virulence than the parental H7N9 virus. In addition, the H7N9 virus, with the exception of the H9N2 reassortants, could effectively replicate in human A549 cells. Our results indicate that PB2, M, and NP are the key virulence genes, together with the surface hemagglutinin (HA) and neuraminidase (NA) proteins, contributing to the high infectivity of the H7N9 virus in humans.IMPORTANCETo date, the novel H7N9 influenza A virus has caused 437 human infections, with approximately 30% mortality. Previous work has primarily focused on the two viral surface proteins, HA and NA, but the contribution of the six internal genes to the high pathogenicity of H7N9 has not been systematically studied. Here, the H9N2 virus was used as a genetic backbone to evaluate the virulence genes of H7N9 virusin vitroandin vivo. Our data indicate that the PB2, M, and NP genes play important roles in viral infection in mice and, together with HA and NA, contribute to the high infectivity of the H7N9 virus in humans.

scholarly journals Emergence of H7N9 Influenza A Virus Resistant to Neuraminidase Inhibitors in Nonhuman Primates

2015 ◽  
Vol 59 (8) ◽  
pp. 4962-4973 ◽  
Author(s):  
Yasushi Itoh ◽  
Shintaro Shichinohe ◽  
Misako Nakayama ◽  
Manabu Igarashi ◽  
Akihiro Ishii ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Influenza A ◽  
Cynomolgus Macaque ◽  
Influenza Virus Infection ◽  
Influenza Viruses ◽  
H7n9 Virus ◽  
Macaque Model ◽  
H7n9 Influenza Virus ◽  
Number Of Patients ◽  
H7n9 Influenza

ABSTRACTThe number of patients infected with H7N9 influenza virus has been increasing since 2013. We examined the efficacy of neuraminidase (NA) inhibitors and the efficacy of a vaccine against an H7N9 influenza virus, A/Anhui/1/2013 (H7N9), isolated from a patient in a cynomolgus macaque model. NA inhibitors (oseltamivir and peramivir) barely reduced the total virus amount because of the emergence of resistant variants with R289K or I219T in NA [residues 289 and 219 in N9 of A/Anhui/1/2013 (H7N9) correspond to 292 and 222 in N2, respectively] in three of the six treated macaques, whereas subcutaneous immunization of an inactivated vaccine derived from A/duck/Mongolia/119/2008 (H7N9) prevented propagation of A/Anhui/1/2013 (H7N9) in all vaccinated macaques. The percentage of macaques in which variant H7N9 viruses with low sensitivity to the NA inhibitors were detected was much higher than that of macaques in which variant H5N1 highly pathogenic influenza virus was detected after treatment with one of the NA inhibitors in our previous study. The virus with R289K in NA was reported in samples from human patients, whereas that with I219T in NA was identified for the first time in this study using macaques, though no variant H7N9 virus was reported in previous studies using mice. Therefore, the macaque model enables prediction of the frequency of emerging H7N9 virus resistant to NA inhibitorsin vivo. Since H7N9 strains resistant to NA inhibitors might easily emerge compared to other influenza viruses, monitoring of the emergence of variants is required during treatment of H7N9 influenza virus infection with NA inhibitors.

scholarly journals Influenza Virus A/Anhui/1/2013 (H7N9) Replicates Efficiently in the Upper and Lower Respiratory Tracts of Cynomolgus Macaques

mBio ◽  
2014 ◽  
Vol 5 (4) ◽  
Author(s):  
Emmie de Wit ◽  
Angela L. Rasmussen ◽  
Friederike Feldmann ◽  
Trenton Bushmaker ◽  
Cynthia Martellaro ◽  
...  
Keyword(s):  
Gene Expression ◽  
Influenza Virus ◽  
Respiratory Tract ◽  
Influenza A Virus ◽  
Influenza A ◽  
Clinical Aspects ◽  
Polymorphonuclear Cells ◽  
H7n9 Virus ◽  
Cynomolgus Macaques ◽  
H7n9 Infection

ABSTRACT In March 2013, three fatal human cases of infection with influenza A virus (H7N9) were reported in China. Since then, human cases have been accumulating. Given the public health importance of this virus, we performed a pathogenicity study of the H7N9 virus in the cynomolgus macaque model, focusing on clinical aspects of disease, radiographic, histological, and gene expression profile changes in the upper and lower respiratory tracts, and changes in systemic cytokine and chemokine profiles during infection. Cynomolgus macaques developed transient, mild to severe disease with radiographic evidence of pulmonary infiltration. Virus replicated in the upper as well as lower respiratory tract, with sustained replication in the upper respiratory tract until the end of the experiment at 6 days after inoculation. Virus shedding occurred mainly via the throat. Histopathological changes in the lungs were similar to those observed in humans, albeit less severe, with diffuse alveolar damage, infiltration of polymorphonuclear cells, formation of hyaline membranes, pneumocyte hyperplasia, and fibroproliferative changes. Analysis of gene expression profiles in lung lesions identified pathways involved in tissue damage during H7N9 infection as well as leads for development of therapeutics targeting host responses rather than virus replication. Overall, H7N9 infection was not as severe in cynomolgus macaques as in humans, supporting the possible role of underlying medical complications in disease severity as discussed for human H7N9 infection (H. N. Gao et al., N. Engl. J. Med. 368:2277–2285, 2013, doi:10.1056/NEJMoa1305584). IMPORTANCE Influenza A virus H7N9 emerged early in 2013, and human cases have continued to emerge since then. Although H7N9 virus-induced disease in humans is often very severe and even lethal, the majority of reported H7N9 cases occurred in older people and people with underlying medical conditions. To better understand the pathogenicity of this virus, healthy cynomolgus macaques were inoculated with influenza A virus H7N9. Cynomolgus macaques were used as a model because the receptor distribution for H7N9 virus in macaques was recently shown to be more similar to that in humans than that of other frequently used animal models. From comparison with previous studies, we conclude that the emerging H7N9 influenza virus was more pathogenic in cynomolgus macaques than seasonal influenza A viruses and most isolates of the pandemic H1N1 virus but less pathogenic than the 1918 Spanish influenza virus or highly pathogenic avian influenza (HPAI) H5N1 virus.

scholarly journals Expression of inflammation-related genes in the lung of BALB/c mice response to H7N9 influenza A virus with different pathogenicity

2016 ◽  
Vol 205 (5) ◽  
pp. 501-509 ◽  
Author(s):  
Meng Yu ◽  
Qingnan Wang ◽  
Wenbao Qi ◽  
Kaizhao Zhang ◽  
Jianxin Liu ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
H7n9 Influenza

scholarly journals H7N9 influenza A virus in turkeys in Minnesota

2015 ◽  
Vol 96 (2) ◽  
pp. 269-276 ◽  
Author(s):  
Camille Lebarbenchon ◽  
Janice C. Pedersen ◽  
Srinand Sreevatsan ◽  
Andrew M. Ramey ◽  
Vivien G. Dugan ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
H7n9 Influenza

scholarly journals The PB1 protein of influenza A virus inhibits the innate immune response by targeting MAVS for NBR1-mediated selective autophagic degradation

2021 ◽  
Vol 17 (2) ◽  
pp. e1009300
Author(s):  
Yan Zeng ◽  
Shuai Xu ◽  
Yanli Wei ◽  
Xuegang Zhang ◽  
Qian Wang ◽  
...  
Keyword(s):  
Immune Response ◽  
Influenza A Virus ◽  
Innate Immune Response ◽  
Influenza A ◽  
Innate Immune ◽  
Negative Regulator ◽  
Poly I:C ◽  
H7n9 Virus ◽  
Autophagic Degradation ◽  
Negative Regulatory Mechanism

Influenza A virus (IAV) has evolved various strategies to counteract the innate immune response using different viral proteins. However, the mechanism is not fully elucidated. In this study, we identified the PB1 protein of H7N9 virus as a new negative regulator of virus- or poly(I:C)-stimulated IFN induction and specifically interacted with and destabilized MAVS. A subsequent study revealed that PB1 promoted E3 ligase RNF5 to catalyze K27-linked polyubiquitination of MAVS at Lys362 and Lys461. Moreover, we found that PB1 preferentially associated with a selective autophagic receptor neighbor of BRCA1 (NBR1) that recognizes ubiquitinated MAVS and delivers it to autophagosomes for degradation. The degradation cascade mediated by PB1 facilitates H7N9 virus infection by blocking the RIG-I-MAVS-mediated innate signaling pathway. Taken together, these data uncover a negative regulatory mechanism involving the PB1-RNF5-MAVS-NBR1 axis and provide insights into an evasion strategy employed by influenza virus that involves selective autophagy and innate signaling pathways.

scholarly journals Possible pandemic threat from new reassortment of influenza A(H7N9) virus in China

2014 ◽  
Vol 19 (6) ◽  
Author(s):  
Z Meng ◽  
R Han ◽  
Y Hu ◽  
Z Yuan ◽  
S Jiang ◽  
...  
Keyword(s):  
Phylogenetic Analysis ◽  
Hong Kong ◽  
Avian Influenza ◽  
Influenza A ◽  
East Coast ◽  
H7n9 Virus ◽  
Pandemic Threat

Avian influenza A(H7N9) virus re-emerged in China in December 2013, after a decrease in the number of new cases during the preceding six months. Reassortment between influenza A(H7N9) and local H9N2 strains has spread from China's south-east coast to other regions. Three new reassortments of A(H7N9) virus were identified by phylogenetic analysis: between A(H7N9) and Zhejiang-derived strains, Guangdong/Hong Kong-derived strains or Hunan-derived A(H9N2) strains. Our findings suggest there is a possible risk that a pandemic could develop.

scholarly journals Identification of two residues within the NS1 of H7N9 influenza A virus that critically affect the protein stability and function

2018 ◽  
Vol 49 (1) ◽  
Author(s):  
Song Wang ◽  
Lanlan Zhang ◽  
Rong Zhang ◽  
Xiaojuan Chi ◽  
Zhou Yang ◽  
...  
Keyword(s):  
Protein Stability ◽  
Influenza A Virus ◽  
Influenza A ◽  
H7n9 Influenza ◽  
And Function
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