Pathogenesis and transmission of human seasonal and swine-origin A(H1) influenza viruses in the ferret model

Abstract

Influenza A viruses (IAVs) in the swine reservoir constantly evolve, resulting in expanding genetic and antigenic diversity of strains that occasionally cause infections in humans and pose a threat of emerging as a strain capable of human-to-human transmission. For these reasons, there is an ongoing need for surveillance and characterization of newly emerging strains to aid pandemic preparedness efforts, particularly for the selection of candidate vaccine viruses and conducting risk assessments. Here, we performed a parallel comparison of the pathogenesis and transmission of genetically and antigenically diverse swine-origin A(H1N1) variant (v) and A(H1N2)v, and human seasonal A(H1N1)pdm09 IAVs using the ferret model. Both groups of viruses were capable of replication in the ferret upper respiratory tract; however, variant viruses were more frequently isolated from the lower respiratory tract as compared to the human-adapted viruses. Regardless of virus origin, observed clinical signs of infection differed greatly between strains, with some viruses causing nasal discharge, sneezing and, in some instances, diarrhea in ferrets. The most striking difference between the viruses was the ability to transmit through the air. Human-adapted viruses were capable of airborne transmission between all ferret pairs. In contrast, only one out of the four tested variant viruses was able to transmit via the air as efficiently as the human-adapted viruses. Overall, this work highlights the need for sustained monitoring of emerging swine IAVs to identify strains of concern such as those that are antigenically different from vaccine strains and that possess adaptations required for efficient respiratory droplet transmission in mammals.

Detection of Airborne Influenza A and SARS-CoV-2 Virus Shedding following Ocular Inoculation of Ferrets

“…1C ). Transient weight loss and fever were observed in all animals, and intermittent sneezing was detected in 3/3 and 2/3 Neb/14 and Anhui/1 virus-inoculated animals, respectively, but clinical signs were overall mild and in agreement with previous assessments of these viruses in ferrets ( 33 , 34 ).…”

“…In contrast, exposure of ferrets by the AR route to Neb/14 IAV led to a robust infection in all exposed animals ( Fig. 3B ), reaching peak mean NW titers comparable to those of ferrets inoculated with high doses of virus by standard intranasal or liquid ocular inoculation routes ( 34 ). Two of three ferrets became productively infected following either OA or AR exposure to Anhui/1 virus ( Table 2 ; Fig.…”

“…To extend this work and further study viral infection dynamics following ocular exposure by examining virus release into the air, we inoculated ferrets by the o.c. route with two different IAV: a contemporary A(H1N1)pdm09 virus derived from the 2009 pandemic well adapted for human infection (A/Nebraska/14/2019 [Neb/14]) and a first-wave low-pathogenic avian influenza (LPAI) A(H7N9) virus (A/Anhui/1/2013 [Anhui/1]) ( 33 , 34 ). Virus transmissibility was assessed by establishing contact 1 day later with an uninfected ferret; contact ferrets were either placed in an adjacent cage with perforated side walls to permit air exchange in the absence of direct or indirect contact (respiratory droplet transmission [RDT] model) or cohoused in the same solid-walled cage (direct contact transmission [DCT] model).…”

“…Neb/14 and Anhui/1 IAV have been shown previously to transmit efficiently after intranasal inoculation in RDT or DCT models, respectively ( 33 , 34 ). Following ocular inoculation, 2/3 (Neb/14, RDT) and 3/3 (Anhui/1, DCT) contact ferrets were productively infected in these settings and seroconverted to homologous virus by the end of the experimental period ( Table 1 ).…”

“…with two IAV and two SCOV2 strains previously shown to replicate efficiently following intranasal (i.n.) inoculation ( 26 , 33 , 34 ). Following inoculation, we examined virus pathogenicity, transmissibility, aerosolized virus shedding profiles, and emergence of variant virus populations during the course of infection.…”