Influenza D virus

Abstract

Influenza D is the only type of influenza virus that mainly affects cattle with frequent spillover to other species. Since the initial description of influenza D virus (IDV) in 2011, the virus has been found to circulate among cattle and swine populations worldwide. Research conducted during the past several years has led to an increased understanding of this novel influenza virus with bovines as a reservoir. In this review, we describe the current knowledge of epidemiology and host range of IDV followed by discussion of infection biology and animal model development for IDV. Finally, we review progress towards understanding of the pathogenesis and host response of IDV as well as developing preventive vaccines for IDV.

Figure 1.. Infectious ecology and host range of influenza D virus.

Influenza D virus utilizes bovines as a primary reservoir with frequent spillover to other animals. The bold black line indicates animals or human that derived influenza D virus or viral genome, while the dotted black line represents animals in which viral antibodies were detected without the evidence of virus isolation or the detection of viral genome. Vector graphic images used in the figure were taken from icon pool of the Microsoft Office and Freepik (www.freepik.com).

Figure 2.. Maximum-likelihood phylogenetic tree of the Hemagglutinin-esterase (HEF) segment of IDV.

IDV D/660, D/OK, and D/Yama2016, and D/Yama2019 lineages were indicated with different colors, respectively. Total 65 full-length HEF nucleotide sequences available in Genbank were used and the tree was constructed in MEGA 6 using the general time reversible+invariable sites substitution model with 1000 replicates of bootstrap performed.

Figure 3.. 9-O-acetylated SA receptors and HEF structure of IDV.

Chemical structures of Neu5,9Ac2 and Neu5Gc9Ac were showed in (A), while structure of IDV D/OK HEF protein trimer (Left, cartoon mode; right, surface mode) (PDB ID:5E65) was presented in the context of binding to an analog of Neu5,9Ac2 Sialic acid (green) (B). Four structural elements involving in the formation of the receptor-binding pocket (RBP) were shown in different colors. Two monomers of a trimer were shown gray with HEF1 and HEF2 subunits of the HEF protein indicated in different colors.

Figure 4.. Evolutionary rate of the HEF gene of influenza D virus.

The evolutionary rate of IDV was estimated using BEAST package, with GTR substitution model, restricted molecular clock, and Bayesian Skyline tree prior model. The optimal models were selected using the path sampling approach in BEAST.