Comparing Influenza Virus Biology for Understanding Influenza D Virus

Abstract

The newest type of influenza virus, influenza D virus (IDV), was isolated in 2011. IDV circulates in several animal species worldwide, causing mild respiratory illness in its natural hosts. Importantly, IDV does not cause clinical disease in humans and does not spread easily from person to person. Here, we review what is known about the host-pathogen interactions that may limit IDV illness. We focus on early immune interactions between the virus and infected host cells in our summary of what is known about IDV pathogenesis. This work establishes a foundation for future research into IDV infection and immunity in mammalian hosts.

Keywords: influenza D virus; innate immunity; interferon; virus pathogenesis.

Figure 1

Natural host range of each influenza virus type. The major species of hosts that each influenza virus type naturally infects is shown, with some overlap existing across influenza virus types. Of note, pigs are the only species known to be infected by all four influenza virus types, and influenza D virus demonstrates the second widest host range behind influenza A virus [16]. Figure created with BioRender.com was adapted from ref. [16]: Kuchipudi and Nissly, 2018.

Figure 2

Influenza virus and viral ribonucleoprotein (vRNP) structure. Examples of IAV and IDV are shown, with vRNP structure for IAV magnified. IAVs are studded with the cell surface proteins hemagglutinin (HA) and neuraminidase (NA), while IDVs are studded with the cell surface protein hemagglutinin esterase fusion (HEF). Influenza viruses also have ion channels (M2 for IAV, DM2 for IDV) along their surface and contain an inner matrix of envelope support proteins (M1 for IAV and IDV). As shown for IAV, each of the RNA gene segments are individually wrapped into vRNP complexes which consist of the viral polymerase complex (for IAV, proteins PB1, PB2, and PA) bound to a viral RNA (vRNA) segment neatly surrounded by several copies of viral nucleoprotein (NP). This structure helps initiate transcription and replication of the viral RNA genome within the nucleus of an infected host cell [30]. Figure created with BioRender.com was generated with assistance from ref. [30]: Dou et al., 2018.

Figure 3

Key players in the innate immune response. Human lung epithelial cells are shown as an example for infected host cells. The innate immune response detects a viral infection at multiple points in the infection cycle through pathogen recognition receptors. These receptors activate the IRF and NFκB pathways, leading to transcription factors that will enter the nucleus and induce the expression of antiviral interferons (IFNs). These IFNs will be secreted from the infected cell and signal through IFN receptors to induce expression of IFN-stimulated genes (ISGs), establishing an antiviral state within the host to limit virus replication and spread [39,41]. (Author dissertation. Labels “nucleus” and “cytoplasm” added from original Dissertation Figure 1.4, ProQuest Document ID 2572559761).