Adaptive Heterosubtypic Immunity to Low Pathogenic Avian Influenza Viruses in Experimentally Infected Mallards

Segovia, Karen; Stallknecht, David E.; Kapczynski, Darrell R.; Stabler, Lisa; Berghaus, Roy D.; Fotjik, Alinde; Latorre‐Margalef, Neus; França, Monique

doi:10.1371/journal.pone.0170335

Cited by 15 publications

(15 citation statements)

References 40 publications

(54 reference statements)

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“…An important outstanding question is why so many rare genetic lineages of surface glycoproteins (H14 and divergent H4, H3, N2, and N8), and unusual subtype combinations were identified in blue-winged teals overwintering in Guatemala (23, 24) and how this diversity relates to variations over time in heterosubtypic immunity in the host population (46, 47). The sources of this diversity also remain unclear.…”

Section: Discussionmentioning

confidence: 99%

Evidence of Intercontinental Spread and Uncommon Variants of Low-Pathogenicity Avian Influenza Viruses in Ducks Overwintering in Guatemala

Gonzalez‐Reiche

Nelson

Angel

et al. 2017

mSphere

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Recent outbreaks of highly pathogenic H7N3, H5Nx, and H7N8 avian influenza viruses in North America were introduced by migratory birds, underscoring the importance of understanding how wild birds contribute to the dissemination and evolution of IAVs in nature. At least four of the main IAV duck host species in North America migrate through or overwinter within a narrow strip of Central America, providing opportunities for diverse IAV lineages to mix and exchange gene segments. By obtaining whole-genome sequences of 68 IAV isolates collected from migratory waterfowl in Guatemala (2010 to 2013), the largest data set available from Central America to date, we detected extensive viral diversity, including gene variants rarely found in North America and gene segments of Eurasian origin. Our findings highlight the need for increased IAV surveillance across the geographical span of bird migration flyways, including Neotropical regions that have been vastly undersampled to date.

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Section: Discussionmentioning

confidence: 99%

Evidence of Intercontinental Spread and Uncommon Variants of Low-Pathogenicity Avian Influenza Viruses in Ducks Overwintering in Guatemala

Gonzalez‐Reiche

Nelson

Angel

et al. 2017

mSphere

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“…The 50% bird infectious doses (BID 50 ) were calculated by the same method. A mock-inoculum consisting of viral transport media was used as previously described [ 21 ].…”

Section: Methodsmentioning

confidence: 99%

“…Effects related to homo- and heterosubtypic immunity have been reported from experimental IAV infections in mallards [ 16 – 20 ]. Previously, we demonstrated that cross-protective immunity between IAV subtypes results in reduced virus shedding in mallards that is positively associated with the phylogenetic relatedness of the hemagglutinin (HA) of the challenge viruses [ 21 , 22 ]. It is also possible that previous IAV infections could affect viral transmission within waterfowl populations by increasing the dose necessary to produce subsequent IAV infections.…”

Section: Introductionmentioning

confidence: 99%

Heterosubtypic immunity increases infectious dose required to infect Mallard ducks with Influenza A virus

et al. 2018

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Previous field and experimental studies have demonstrated that heterosubtypic immunity (HSI) is a potential driver of Influenza A virus (IAV) prevalence and subtype diversity in mallards. Prior infection with IAV can reduce viral shedding during subsequent reinfection with IAV that have genetically related hemagglutinins (HA). In this experiment, we evaluated the effect of HSI conferred by an H3N8 IAV infection against increasing challenge doses of closely (H4N6) and distantly (H6N2) related IAV subtypes in mallards. Two groups of thirty 1-month-old mallards each, were inoculated with 105.9 50% embryo infectious doses (EID50) of an H3N8 virus or a mock-inoculum. One month later, groups of five birds each were challenged with increasing doses of H4N6 or H6N2 virus; age-matched, single infection control ducks were included for all challenges. Results demonstrate that naïve birds were infected after inoculation with 103 and 104 EID50 doses of the H4N6 or H6N2 virus, but not with 102 EID50 doses of either IAV. In contrast, with birds previously infected with H3N8 IAV, only one duck challenged with 104 EID50 of H4N6 IAV was shedding viral RNA at 2 days post-inoculation, and with H6N2 IAV, only birds challenged with the 104 EID50 dose were positive to virus isolation. Viral shedding in ducks infected with H6N2 IAV was reduced on days 2 and 3 post-inoculation compared to control birds. To explain the differences in the dose necessary to produce infection among H3-primed ducks challenged with H4N6 or H6N2 IAV, we mapped the amino acid sequence changes between H3 and H4 or H6 HA on predicted three-dimensional structures. Most of the sequence differences occurred between H3 and H6 at antigenic sites A, B, and D of the HA1 region. These findings demonstrate that the infectious dose necessary to infect mallards with IAV can increase as a result of HSI and that this effect is most pronounced when the HA of the viruses are genetically related.

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“… 3 , 4 The mechanisms underlying these seasonal patterns are not known, but one possibility is that they are driven by the induction of humoral cross protective immunity after early infections. 5 , 6 Given the capacity for influenza viruses to spread via migratory avian hosts, as observed when H5N8 spread across North America in 2015, 7 it is important to study the mechanics underlying these seasonal dynamics. This is specifically interesting in light of cross-reactivity/cross-protection within group 1 (H1, H2, H5, H6, H8, H9, H11, H12, H13, H16, H17 and H18) and group 2 (H3, H4, H7, H10, H14 and H15) hemagglutinnin (HA) expressing viruses by stalk-reactive monoclonal antibodies isolated from humans and mice.…”

Section: Introductionmentioning

confidence: 99%

Development of an influenza virus protein microarray to measure the humoral response to influenza virus infection in mallards

Meade

Latorre‐Margalef

Stallknecht

et al. 2017

Emerging Microbes & Infections

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Avian influenza viruses pose a serious zoonotic threat, in part because current seasonal influenza virus vaccines only offer strain-specific protection, instead of heterosubtypic or universal protection against influenza virus infection. Understanding the humoral response to vaccination and natural infection in the broadest context possible is important to developing defenses against influenza zoonosis. Protein microarrays are a novel platform well suited to assaying the humoral immune response broadly and efficiently. We developed an influenza virus protein microarray (IVPM) that could be used to assay sera from many species, including humans. Waterfowl such as mallard ducks are natural reservoirs for many influenza A viruses, but their humoral immune response to infection is poorly understood. To establish this technology, we assayed sera from mallards experimentally infected with two low-pathogenic common avian influenza viruses (H3N8 and H4N5) for reactivity to influenza virus hemagglutinin (HA) by IVPM. The IVPM results correlated well with results from an established enzyme-linked immunosorbent assay, supporting the validity of the IVPM as a serological assay in influenza virus research. Interestingly, successive infection with H3N8 followed by H4N5 virus in mallard ducks induced antibodies that were broadly reactive against group 2 hemagglutinins. We also analyzed sera from wild mallards and observed serological evidence for infection in those sera. With serological information, it may be possible to infer infection history of wild avian species and gain a better understanding of the infection dynamics of influenza viruses in their natural reservoir. This might ultimately lead to interventions that enhance our pandemic preparedness.

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Adaptive Heterosubtypic Immunity to Low Pathogenic Avian Influenza Viruses in Experimentally Infected Mallards

Cited by 15 publications

References 40 publications

Evidence of Intercontinental Spread and Uncommon Variants of Low-Pathogenicity Avian Influenza Viruses in Ducks Overwintering in Guatemala

Evidence of Intercontinental Spread and Uncommon Variants of Low-Pathogenicity Avian Influenza Viruses in Ducks Overwintering in Guatemala

Heterosubtypic immunity increases infectious dose required to infect Mallard ducks with Influenza A virus

Development of an influenza virus protein microarray to measure the humoral response to influenza virus infection in mallards

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