Abstract
Studies of influenza transmission are necessary to predict the pandemic potential of emerging influenza viruses. Currently, both ferrets and guinea pigs are used in such studies, but these species are distantly related to humans. Nonhuman primates (NHP) share a close phylogenetic relationship with humans and may provide an enhanced means to model the virological and immunological events in influenza virus transmission. Here, for the first time, it was demonstrated that a human influenza virus isolate can productively infect and be transmitted between common marmosets (Callithrix jacchus), a New World monkey species. We inoculated four marmosets with the 2009 pandemic virus A/California/07/2009 (H1N1pdm) and housed each together with a naïve cage mate. We collected bronchoalveolar lavage and nasal wash samples from all animals at regular intervals for three weeks post-inoculation to track virus replication and sequence evolution. The unadapted 2009 H1N1pdm virus replicated to high titers in all four index animals by 1 day post-infection. Infected animals seroconverted and presented human-like symptoms including sneezing, nasal discharge, labored breathing, and lung damage. Transmission occurred in one cohabitating pair. Deep sequencing detected relatively few genetic changes in H1N1pdm viruses replicating in any infected animal. Together our data suggest that human H1N1pdm viruses require little adaptation to replicate and cause disease in marmosets, and that these viruses can be transmitted between animals. Marmosets may therefore be a viable model for studying influenza virus transmission.
Highlights
Studies of influenza virus transmission, pathogenesis and immunity rely on animal models to understand processes that are difficult or impossible to investigate in humans
One animal in each pair was inoculated with 16108 plaque-forming units (PFU) of an influenza A/California/07/2009 stock virus grown on Madin-Darby canine kidney (MDCK) cells
Bronchoalveolar lavage (BAL) and nasal wash (NW) samples were collected at regular intervals for three weeks post-inoculation, and viral replication was monitored by QRT-PCR and plaque assay
Summary
Studies of influenza virus transmission, pathogenesis and immunity rely on animal models to understand processes that are difficult or impossible to investigate in humans. Ferrets, guinea pigs and rhesus macaques have all been used to study various aspects of human infection with influenza viruses [1]. Ferrets are a favored model system due to their susceptibility to unadapted human influenza strains, their development of human-like symptoms during infection and their susceptibility to respiratory droplet transmission. Macaque monkeys have been used in studies of influenza pathogenesis and immunity [1], transmission of influenza viruses between macaques has not been documented, and there is currently no NHP model for influenza transmission studies. Marmosets are small New World monkeys native to eastern Brazil that breed well in captivity and are already used as models for other viral pathogens, including hepatitis A virus, GB virus B, measles virus, and several hemorrhagic fever and herpesviruses [3]
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