Biological features of novel avian influenza A (H7N9) virus

Abstract

Human infection associated with a novel reassortant avian influenza H7N9 virus has recently been identified in China. A total of 132 confirmed cases and 39 deaths have been reported. Most patients presented with severe pneumonia and acute respiratory distress syndrome. Although the first epidemic has subsided, the presence of a natural reservoir and the disease severity highlight the need to evaluate its risk on human public health and to understand the possible pathogenesis mechanism. Here we show that the emerging H7N9 avian influenza virus poses a potentially high risk to humans. We discover that the H7N9 virus can bind to both avian-type (α2,3-linked sialic acid) and human-type (α2,6-linked sialic acid) receptors. It can invade epithelial cells in the human lower respiratory tract and type II pneumonocytes in alveoli, and replicated efficiently in ex vivo lung and trachea explant culture and several mammalian cell lines. In acute serum samples of H7N9-infected patients, increased levels of the chemokines and cytokines IP-10, MIG, MIP-1β, MCP-1, IL-6, IL-8 and IFN-α were detected. We note that the human population is naive to the H7N9 virus, and current seasonal vaccination could not provide protection.

Prevention of influenza by targeting host receptors using engineered proteins

“…Human influenza viruses such as the 2009 pandemic H1N1 virus recognize α-2,6-linked sialic acid receptors present in the upper respiratory tract, whereas avian influenza viruses such as H5N1 predominantly recognize α-2,3-linked sialic acid receptors, which are present in the human lower respiratory tract as well (12,13). The recently emerged human H7N9 influenza virus is unusual in recognizing both types of receptors and therefore has the possibility of sustained human-to-human transmission and pandemic potential (14,15).…”

Cytokines and chemokines in mild/asymptomatic cases infected with avian influenza A (H7N9) virus

“…Earlier studies showed that IP-10, IL-6, IL-8, IL-10, MCP-1, MIG and MIP-1b were dramatically increased in severe H7N9 cases and H5N1 cases compared to controls (Peiris et al, 2004;de Jong et al, 2006;Chi et al, 2013;Zhou et al, 2013;Shen et al, 2014;Wang et al, 2014b;Wu et al, 2014). However, these cytokines in mild/asymptomatic H7N9 cases were similar to those in controls except that the level of IP-10 increased very slightly.…”

“…Previous studies with highly pathogenic avian influenza A (H5N1) virus as well as pandemic (H1N1) 2009 virus suggested that poor prognosis in humans with these viruses might be attributed to a cytokine storm or hypercytokinaemia in the host (Peiris et al, 2004;de Jong et al, 2006;To et al, 2010). Some studies with H7N9 virus also showed the presence of high levels of a series of cytokines and chemokines, such as IP-10, IL-6, IL-8, IL-10, MCP-1, MIG and MIP-1b, in human infections with severe disease with or without fatal outcomes (Chi et al, 2013;Zhou et al, 2013;Shen et al, 2014;Wang et al, 2014b;Wu et al, 2014). It should be noted that investigation on the profiles of cytokines and chemokines induced in mild/asymptomatic cases will aid in assessing their role in mild/asymptomatic versus severe/fatal outcomes of infection with H7N9 and the role of innate immunity and provides a new perspective on the evaluation of prognosis and the innovation of treatment.…”

T cell epitope engineering: an avian H7N9 influenza vaccine strategy for pandemic preparedness and response

“…Any cross-reactive memory B and T cells would be present at frequencies too low to confer protective antibody immunity by seasonal vaccination. 18 As a consequence, avian influenza vaccines require higher doses than seasonal vaccines or adjuvant formulation to stimulate robust immune responses. 18 …”

“…18 As a consequence, avian influenza vaccines require higher doses than seasonal vaccines or adjuvant formulation to stimulate robust immune responses. 18 …”