Respiratory Tract Explant Infection Dynamics of Influenza A Virus in California Sea Lions, Northern Elephant Seals, and Rhesus Macaques

• Published in: Journal of virology Vol. 95; no. 16; p. e0040321
• Main Authors: Liu, Hongwei, Plancarte, Magdalena, Ball, Erin E, Weiss, Christopher M, Gonzales-Viera, Omar, Holcomb, Karen, Ma, Zhong-Min, Allen, A Mark, Reader, J Rachel, Duignan, Pádraig J, Halaska, Barbie, Khan, Zenab, Kriti, Divya, Dutta, Jayeeta, van Bakel, Harm, Jackson, Kenneth, Pesavento, Patricia A, Boyce, Walter M, Coffey, Lark L
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 26.07.2021
• Subjects: Animals; Dogs; Host Specificity; Influenza A virus - classification; Influenza A virus - physiology; Kinetics; Macaca mulatta; Madin Darby Canine Kidney Cells; Models, Biological; Orthomyxoviridae Infections - virology; Respiratory System - pathology; Respiratory System - virology; Respiratory Tract Infections - virology; Sea Lions; Seals, Earless; Species Specificity; Viral Load; Viral Tropism; Virus-Cell Interactions; rhesus macaque; tropism; kinetics; respiratory viruses; marine mammal; infection dynamics; explant; influenza A virus
• ISSN: 0022-538X; 1098-5514
• DOI: 10.1128/JVI.00403-21

To understand susceptibility of wild California sea lions and Northern elephant seals to influenza A virus (IAV), we developed an respiratory explant model and used it to compare infection kinetics for multiple IAV subtypes. We first established the approach using explants from colonized rhesus macaques, a model for human IAV. Trachea, bronchi, and lungs from 11 California sea lions, 2 Northern elephant seals, and 10 rhesus macaques were inoculated within 24 h postmortem with 6 strains representing 4 IAV subtypes. Explants from the 3 species showed similar IAV infection kinetics, with peak viral titers 48 to 72 h post-inoculation that increased by 2 to 4 log PFU/explant relative to the inoculum. Immunohistochemistry localized IAV infection to apical epithelial cells. These results demonstrate that respiratory tissue explants from wild marine mammals support IAV infection. In the absence of the ability to perform experimental infections of marine mammals, this culture of respiratory tissues mirrors the environment and serves as a tool to study IAV susceptibility, host range, and tissue tropism. Although influenza A virus can infect marine mammals, a dearth of marine mammal cell lines and ethical and logistical challenges prohibiting experimental infections of living marine mammals mean that little is known about IAV infection kinetics in these species. We circumvented these limitations by adapting a respiratory tract explant model first to establish the approach with rhesus macaques and then for use with explants from wild marine mammals euthanized for nonrespiratory medical conditions. We observed that multiple strains representing 4 IAV subtypes infected trachea, bronchi, and lungs of macaques and marine mammals with variable peak titers and kinetics. This model can define infection dynamics for IAV in marine mammals. Further, use of explants from animals euthanized for other reasons reduces use of animals in research.