Influenza C and D Viruses Demonstrated a Differential Respiratory Tissue Tropism in a Comparative Pathogenesis Study in Guinea Pigs

Authors

Chithra C. Sreenivasan, University of Kentucky
Runxia Liu, South Dakota State University
Rongyuan Gao, South Dakota State University
Yicheng Guo, Columbia University
Ben M. Hause, South Dakota State University
Milton Thomas, South Dakota State University
Ahsan Naveed, University of Kentucky
Travis Clement, South Dakota State University
Dana Rausch, South Dakota State University
Jane Christopher-Hennings, South Dakota State University
Eric Nelson, South Dakota State University
Julian Druce, Victorian Infectious Diseases Reference Laboratory
Miaoyun Zhao, University of Nebraska—Lincoln, LincolnFollow
Radhey S. Kaushik, South Dakota State University
Qingsheng Li, University of Nebraska - LincolnFollow
Zizhang Sheng, Columbia University
Dan Dan, University of Kentucky
Feng Li, University of Kentucky

Document Type

Article

Date of this Version

5-18-2023

Citation

Influenza C and D Viruses in Guinea Pigs. Journal of Virology June 2023 Volume 97 Issue 6. 10.1128/jvi.00356-23

Comments

Used by permission.

Abstract

Influenza C virus (ICV) is increasingly associated with community-acquired pneumonia (CAP) in children and its disease severity is worse than the influenza B virus, but similar to influenza A virus associated CAP. Despite the ubiquitous infection landscape of ICV in humans, little is known about its replication and pathobiology in animals. The goal of this study was to understand the replication kinetics, tissue tropism, and pathogenesis of human ICV (huICV) in comparison to the swine influenza D virus (swIDV) in guinea pigs. Intranasal inoculation of both viruses did not cause clinical signs, however, the infected animals shed virus in nasal washes. The huICV replicated in the nasal turbinates, soft palate, and trachea but not in the lungs while swIDV replicated in all four tissues. A comparative analysis of tropism and pathogenesis of these two related seven-segmented influenza viruses revealed that swIDV-infected animals exhibited broad tissue tropism with an increased rate of shedding on 3, 5, and 7 dpi and high viral loads in the lungs compared to huICV. Seroconversion occurred late in the huICV group at 14 dpi, while swIDV-infected animals seroconverted at 7 dpi. Guinea pigs infected with huICV exhibited mild to moderate inflammatory changes in the epithelium of the soft palate and trachea, along with mucosal damage and multifocal alveolitis in the lungs. In summary, the replication kinetics and pathobiological characteristics of ICV in guinea pigs agree with the clinical manifestation of ICV infection in humans, and hence guinea pigs could be used to study these distantly related influenza viruses.