An Infant Mouse Model of Influenza Virus Transmission Demonstrates the Role of Virus-Specific Shedding, Humoral Immunity, and Sialidase Expression by Colonizing Streptococcus pneumoniae

Abstract

This study provides insight into the role of the virus strain, age, immunity, and URT flora on IAV shedding and transmission efficiency. Using the infant mouse model, we found that (i) differences in viral shedding of various IAV strains are dependent on specific hemagglutinin (HA) and/or neuraminidase (NA) proteins, (ii) host age plays a key role in the efficiency of IAV transmission, (iii) levels of IAV-specific immunoglobulins are necessary to limit infectiousness, transmission, and susceptibility to IAV, and (iv) expression of sialidases by colonizing S. pneumoniae antagonizes transmission by limiting the acquisition of IAV in recipient hosts. Our findings highlight the need for strategies that limit IAV shedding and the importance of understanding the function of the URT bacterial composition in IAV transmission. This work reinforces the significance of a tractable animal model to study both viral and host traits affecting IAV contagion and its potential for optimizing vaccines and therapeutics that target disease spread.

Pneumococcal colonization impairs nasal and lung mucosal immune responses to Live Attenuated Influenza Vaccination in adults

“…In our study, Spn colonised volunteers upregulated genes involved in TLR2 signalling, RIG-I/MDA5 mediated induction of IFN-α/β and IFN-α/β pathways before exposure to LAIV and exhibited impaired inflammatory responses post vaccination. Despite these observations, any alteration of viral replication cycle mediated by pneumoniae-IAV coinfection model 47 . In light of these observations, it would also be interesting to investigate to what extent symptoms and inflammation caused by wild type influenza viruses are altered by concurrent Spn colonization in humans.…”

Can animal models really teach us anything about pneumonia? Pro

“…For example, using deletion mutants, site-specific roles were identified for pneumococcal virulence determinants, which helps explain why pneumococcal strains vary in their ability to cause disease at different anatomical sites [45,46]. Similarly, dual infection animal models have characterised how host and pathogen factors affect influenza-induced transmission of S. pneumoniae and the efficacy of vaccination in blocking this key event [47,48].…”

Quantifying between-Host Transmission in Influenza Virus Infections

“…To address the inconsistency of transmission in adult mouse models, Ortigoza et al (2018) began with infant mice to track the transmission of influenza virus. Infant mice ∼7 days old efficiently transmitted the laboratory strain A/X-31(H3N2) to their cocaged infant recipients, whereas newly weaned and adult mice (>28 d) failed to transmit the virus altogether.…”

“…The infant mouse transmission model was similarly used to study effects on transmission of the precolonization of Streptococcus pneumoniae, because in human children, S. pneumoniae often precedes influenza A virus infections (Mc-Cullers 2006;Morris et al 2017). Here, recipient mice showed a lower incidence of influenza infection when prior colonization of S. pneumoniae occurred, further highlighting the potential importance of the host's microbiome in limiting the transmission of influenza (Ortigoza et al 2018). It is reasonable to speculate, however, that other bacterial species may help influenza transmit to other hosts.…”