Wild aquatic bird avian influenza virus infections in mammals
Driskell, Elizabeth Ann
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Numerous cases of direct transmission of avian H5, H7, and H9 influenza viruses from birds to humans have stimulated concern regarding a potential avian influenza pandemic. The purpose of this research is to evaluate the potential of avian influenza viruses (AIVs) from wild aquatic birds to replicate in mammals with the greater goal of assessing indirect or direct AIV transmission risk to humans. Four hundred nineteen AIV isolates from the reservoir hosts, waterfowl and shorebirds, were examined in vitro via plaquing in Madin-Darby canine kidney (MDCK) cells. Of these isolates, 93% replicated in MDCK cells and 28% of these isolates plaqued without the addition of trypsin. Twenty eight of these isolates were further examined in vivo in a BALB/c mouse model. The ability to replicate in the lower respiratory tract (lungs) of mice was highly variable and isolate dependent; however, many isolates were able to replicate to high titers in the mouse lung and induce pulmonary pathology in the absence of overt clinical disease. Two isolates that exhibited robust replication in the mouse lung were further characterized in ferrets. Both of these isolates resulted in upper and lower respiratory tract infection with nasal shedding, respiratory pathology, and seroconversion with minimal clinical disease. One of these isolates was also able to transmit from infected to naïve ferrets via direct contact. The two isolates examined in ferrets were also examined in domestic cats. Experimental infection of domestic cats with these two different shorebird AIVs did not result in disease, led to variable pharyngeal viral shedding with one of the viruses, and resulted in low levels of seroconversion of all cats. Taken together, these results indicate that wild bird influenza viruses have the ability to infect mammals without adaptation in domestic birds or other mammals; although the ability to infect mammals appears to be extremely variable based on the isolate and productive infections and transmission would likely be dependent on the magnitude of viral exposure and resultant shedding. Not only was the capacity for direct transmission demonstrated, but such events in domestic cats could lead to adaptation to or reassortment in this species.