Low Pathogenic Avian Influenza Isolates from Wild Birds Replicate and Transmit via Contact in Ferrets without Prior Adaptation

Direct transmission of avian influenza viruses to mammals has become an increasingly investigated topic during the past decade; however, isolates that have been primarily investigated are typically ones originating from human or poultry outbreaks. Currently there is minimal comparative information on the behavior of the innumerable viruses that exist in the natural wild bird host. We have previously demonstrated the capacity of numerous North American avian influenza viruses isolated from wild birds to infect and induce lesions in the respiratory tract of mice. In this study, two isolates from shorebirds that were previously examined in mice (H1N9 and H6N1 subtypes) are further examined through experimental inoculations in the ferret with analysis of viral shedding, histopathology, and antigen localization via immunohistochemistry to elucidate pathogenicity and transmission of these viruses. Using sequence analysis and glycan binding analysis, we show that these avian viruses have the typical avian influenza binding pattern, with affinity for cell glycoproteins/glycolipids having terminal sialic acid (SA) residues with α 2,3 linkage [Neu5Ac(α2,3)Gal]. Despite the lack of α2,6 linked SA binding, these AIVs productively infected both the upper and lower respiratory tract of ferrets, resulting in nasal viral shedding and pulmonary lesions with minimal morbidity. Moreover, we show that one of the viruses is able to transmit to ferrets via direct contact, despite its binding affinity for α 2,3 linked SA residues. These results demonstrate that avian influenza viruses, which are endemic in aquatic birds, can potentially infect humans and other mammals without adaptation. Finally this work highlights the need for additional study of the wild bird subset of influenza viruses in regard to surveillance, transmission, and potential for reassortment, as they have zoonotic potential

Confining CO molecules in stable orbits

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Comparison of critical amino acids involved in receptor specificity of influenza hemagglutinin.

a<p>Hemagglutinin residues using H3 numbering.</p

Morbidity, seroconversion, and respiratory viral replication of ferrets inoculated with wild bird avian influenza viruses H1N9 and H6N1.

a<p>Temperature is in degrees Celsius.</p>b<p>Limit of detection for nasal wash 1.5 log₁₀ TCID₅₀/mL.</p>c<p>Limit of detection for lung day 7 pi both viruses and day 3 pi for H6N1 is 1.3 TCID₅₀/g; for days 2 and 3 pi for H1N9 is 1.0 TCID₅₀/g.</p>d<p>One control ferret potentially had an unrelated infection, but remained influenza seronegative.</p>e<p>Not done.</p>f<p>Tested against both H6N1 and H1N9.</p

Presence of influenza virus in ferret organs by virus isolation in ECEs for ferrets infected with wild bird avian influenza viruses H6N1 and H1N9.

<p>For each organ listed, the number of animals with a positive isolation of virus out of the number of animals tested is shown.</p>a<p>Not done for this sample.</p

Glycan binding analysis of wild bird avian or human influenza viruses.

<p>Influenza viruses were propagated in Madin-Darby kidney cells, purified on a 25% sucrose cushion by ultracentrifugation, and labeled with Alexa488 before being applied to the microarray. The data was organized based on Neu5GC, α2,3 SA, α2,6 SA and α2,8 SA glycan structures and represented by different color schemes. Glycan microarray binding analysis was performed by Core H of the Consortium for Functional Glycomics. A) A/Ruddy Turnstone/DE/1171/02 (H1N9), B) A/Ruddy Turnstone/DE/892/02 (H6N1), C) A/Pennsylvania/08/2008 (H1N1).</p

Agglutination of erythrocytes from different animal species by human and avian influenza viruses.

a<p>Hemagglutination titers are provide as the reciprocal of the highest virus dilution generating agglutination.</p