The Orthomyxoviruses have three types of influenza viruses, termed as A, B, and C, that are classified according to the antigenic differences between their nucleoprotein (NP) and matrix 1 (M1) proteins as demonstrated in the traditional serological assays. We identified a novel influenza virus from swine exhibiting influenza-like illness. Its overall amino acid sequence shares approximately 50 % identity with that of ICV. Phylogenetic analysis further found that it is most closely related to ICV, rather than to IAV and IBV. However, the distance between the new virus and ICV was similar to the differences between IAV and IBV for the most of genomic segments. Recently, we also found the prevalence of C/OK-like virus in cattle. The incidences of C/OK and C/OK-like viruses in both cattle and swine provides strong evidence of cross-species transmission, highlighting their potential threat to human health because of closely physical contacts between humans and these farm animals. Additionally, this group of viruses may undergo reassortment with currently circulating human ICV to generate new antigenic variants that could pose a threat to human and animal health. The potential impact on human health and the novel properties in biology and molecular genetics warrant further investigation into this group of new viruses, which form the foundation of this R21 proposal. Major goals of this R21 project are to develop reverse genetics systems (RGS) for these novel viruses, identify their receptor, elucidate a functional role of vira HE protein in cell tropism and temperature restriction of virus replication, define viral mutation rates, and importantly determine whether human ICV and these new viruses can undergo reassortment to produce viable viruses. Successful completion of this project will provide novel insights to evolution, biology, and genetics of this new group of emerging viruses that have a potential threat to human health.

Public Health Relevance

We recently discovered a new group of influenza C-like viruses in swine and cattle. Prevalence of these novel viruses in both cattle and swine provides strong evidence of cross-species transmission, highlighting their potential threat to human health because of closely physical contacts between humans and these farm animals. The goal of this R21 project is to further study biology and molecular genetics of these emerging viruses along with the development of reverse genetics systems.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21AI107379-02
Application #
8912975
Study Section
Virology - B Study Section (VIRB)
Program Officer
Hauguel, Teresa M
Project Start
2014-08-15
Project End
2016-07-31
Budget Start
2015-08-01
Budget End
2016-07-31
Support Year
2
Fiscal Year
2015
Total Cost
Indirect Cost
Name
South Dakota State University
Department
Biology
Type
Earth Sciences/Resources
DUNS #
929929743
City
Brookings
State
SD
Country
United States
Zip Code
57007
Thomas, Milton; Pierson, Max; Uprety, Tirth et al. (2018) Comparison of Porcine Airway and Intestinal Epithelial Cell Lines for the Susceptibility and Expression of Pattern Recognition Receptors upon Influenza Virus Infection. Viruses 10:
Nedland, H; Wollman, J; Sreenivasan, C et al. (2018) Serological evidence for the co-circulation of two lineages of influenza D viruses in equine populations of the Midwest United States. Zoonoses Public Health 65:e148-e154
Wan, Yanmin; Kang, Guobin; Sreenivasan, Chithra et al. (2018) A DNA Vaccine Expressing Consensus Hemagglutinin-Esterase Fusion Protein Protected Guinea Pigs from Infection by Two Lineages of Influenza D Virus. J Virol 92:
Yu, Jieshi; Hika, Busha; Liu, Runxia et al. (2017) The Hemagglutinin-Esterase Fusion Glycoprotein Is a Primary Determinant of the Exceptional Thermal and Acid Stability of Influenza D Virus. mSphere 2:
Zhai, Shao-Lun; Zhang, He; Chen, Sheng-Nan et al. (2017) Influenza D Virus in Animal Species in Guangdong Province, Southern China. Emerg Infect Dis 23:1392-1396
Mitra, Namita; Cernicchiaro, Natalia; Torres, Siddartha et al. (2016) Metagenomic characterization of the virome associated with bovine respiratory disease in feedlot cattle identified novel viruses and suggests an etiologic role for influenza D virus. J Gen Virol 97:1771-84
Quast, Megan; Sreenivasan, Chithra; Sexton, Gabriel et al. (2015) Serological evidence for the presence of influenza D virus in small ruminants. Vet Microbiol 180:281-285
Collin, Emily A; Sheng, Zizhang; Lang, Yuekun et al. (2015) Cocirculation of two distinct genetic and antigenic lineages of proposed influenza D virus in cattle. J Virol 89:1036-42
Sreenivasan, Chithra; Thomas, Milton; Sheng, Zizhang et al. (2015) Replication and Transmission of the Novel Bovine Influenza D Virus in a Guinea Pig Model. J Virol 89:11990-2001
Hause, Ben M; Collin, Emily A; Liu, Runxia et al. (2014) Characterization of a novel influenza virus in cattle and Swine: proposal for a new genus in the Orthomyxoviridae family. MBio 5:e00031-14

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