scholarly journals Local patterns of spread of influenza A(H3N2) virus in coastal Kenya over a one-year period revealed through virus sequence data

2021 ◽  
Author(s):  
D. Collins Owuor ◽  
Joyce M. Ngoi ◽  
Festus M. Nyasimi ◽  
Nickson Murunga ◽  
Joyce U. Nyiro ◽  
...  
Keyword(s):  
Influenza A ◽  
Spatial Clustering ◽  
Sequence Data ◽  
H3n2 Virus ◽  
Influenza A Viruses ◽  
Tropical Regions ◽  
Local Populations ◽  
One Year ◽  
The One ◽  
Virus Genomes

The patterns of spread of influenza A viruses in local populations in tropical and sub-tropical regions are unclear due to sparsity of representative spatiotemporal sequence data. We sequenced and analyzed 58 influenza A(H3N2) virus genomes sampled between December 2015 and December 2016 from nine health facilities within the Kilifi Health and Demographic Surveillance System (KHDSS), a predominantly rural region, covering approximately 891 km2 along the Kenyan coastline. The genomes were compared with 1,571 contemporaneous global sequences from 75 countries. We observed at least five independent introductions of A(H3N2) viruses into the region during the one-year period, with the importations originating from Africa, Europe, and North America. We also inferred 23 virus location transition events between the nine facilities included in the study. International virus imports into the study area were captured at the facilities of Chasimba, Matsangoni, Mtondia, and Mavueni, while all four exports from the region were captured from the Chasimba facility, all occurring to Africa destinations. A strong spatial clustering of virus strains at all locations was observed associated with local evolution. Our study shows that influenza A(H3N2) virus epidemics in local populations appear to be characterized by limited introductions followed by significant local spread and evolution.

scholarly journals Chimeric Hemagglutinin-Based Live-Attenuated Vaccines Confer Durable Protective Immunity against Influenza A Viruses in a Preclinical Ferret Model

Vaccines ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 40
Author(s):  
Wen-Chun Liu ◽  
Raffael Nachbagauer ◽  
Daniel Stadlbauer ◽  
Shirin Strohmeier ◽  
Alicia Solórzano ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Influenza A ◽  
Influenza Virus Infection ◽  
Influenza Virus Vaccine ◽  
Antibody Responses ◽  
Upper Respiratory Tract ◽  
Influenza A Viruses ◽  
Humoral And Cellular Immunity ◽  
Stalk Domain ◽  
One Year

Epidemic or pandemic influenza can annually cause significant morbidity and mortality in humans. We developed novel chimeric hemagglutinin (cHA)-based universal influenza virus vaccines, which contain a conserved HA stalk domain from a 2009 pandemic H1N1 (pH1N1) strain combined with globular head domains from avian influenza A viruses. Our previous reports demonstrated that prime-boost sequential immunizations induced robust antibody responses directed toward the conserved HA stalk domain in ferrets. Herein, we further followed vaccinated animals for one year to compare the efficacy and durability of these vaccines in the preclinical ferret model of influenza. Although all cHA-based immunization regimens induced durable HA stalk-specific and heterosubtypic antibody responses in ferrets, sequential immunization with live-attenuated influenza virus vaccines (LAIV-LAIV) conferred the best protection against upper respiratory tract infection by a pH1N1 influenza A virus. The findings from this study suggest that our sequential immunization strategy for a cHA-based universal influenza virus vaccine provides durable protective humoral and cellular immunity against influenza virus infection.

Rapid diagnosis of influenza A infection by direct immunofluorescence of nasopharyngeal aspirates in adults

1979 ◽  
Vol 9 (6) ◽  
pp. 688-692
Author(s):  
J A Daisy ◽  
F S Lief ◽  
H M Friedman
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Virus Isolation ◽  
Fluorescent Antibody ◽  
Positive Culture ◽  
H3n2 Virus ◽  
Direct Immunofluorescence ◽  
The One ◽  
Immunofluorescent Test ◽  
Culture Negative

The efficacy for direct immunofluorescence of a commercial conjugate for influenza A virus prepared against whole A/Udorn (H3NS) virus was studied. The conjugate was specific for influenza A virus, but its sensitivity varied depending upon the strain of influenza A tested. Nasopharyngeal aspirates collected from 25 patients during an outbreak of influenza were examined for viral antigen with the conjugates and inoculated onto monkey kidney (MK) cells for virus isolation. Fifteen patients had isolates for influenza A/USSR/90/77 (H1N1); nasopharyngeal secretions were fluorescent antibody positive in 12. Fluorescent antibody was copositive with culture in 11/15 patients (73.3%) and conegative in 9/10 (90%). The one fluorescent antibody-positive, culture-negative patient had negative serology for influenza A and the fluorescent antibody result was considered to be a false positive. At a 1:10 dilution, the conjugate stained nasopharyngeal and MK cells infected with A/USSR (H1N1) 2 to 3+, whereas cells infected with H3N2 virus stained 4+. A conjugate made specifically against the ribonucleoprotein antigen, which is universal to all influenza A strains, may improve the sensitivity of the direct immunofluorescent test.

scholarly journals Improving pandemic influenza risk assessment

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Colin A Russell ◽  
Peter M Kasson ◽  
Ruben O Donis ◽  
Steven Riley ◽  
John Dunbar ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Pandemic Influenza ◽  
Influenza A ◽  
Sequence Data ◽  
Virus Genome ◽  
Influenza Viruses ◽  
Influenza Surveillance ◽  
Human Influenza ◽  
Influenza A Viruses ◽  
Virus Genotype

Assessing the pandemic risk posed by specific non-human influenza A viruses is an important goal in public health research. As influenza virus genome sequencing becomes cheaper, faster, and more readily available, the ability to predict pandemic potential from sequence data could transform pandemic influenza risk assessment capabilities. However, the complexities of the relationships between virus genotype and phenotype make such predictions extremely difficult. The integration of experimental work, computational tool development, and analysis of evolutionary pathways, together with refinements to influenza surveillance, has the potential to transform our ability to assess the risks posed to humans by non-human influenza viruses and lead to improved pandemic preparedness and response.

scholarly journals Protective Memory Responses Are Modulated by Priming Events prior to Challenge

2009 ◽  
Vol 84 (2) ◽  
pp. 1047-1056 ◽  
Author(s):  
John A. Rutigliano ◽  
Melissa Y. Morris ◽  
Wen Yue ◽  
Rachael Keating ◽  
Richard J. Webby ◽  
...  
Keyword(s):  
T Cell ◽  
Influenza A ◽  
T Cell Response ◽  
H3n2 Virus ◽  
Cell Mediated Immunity ◽  
Influenza A Viruses ◽  
Differential Survival ◽  
Virus Challenge ◽  
Response Characteristics ◽  
H5n1 Influenza

ABSTRACT Human infections with highly pathogenic H5N1 avian influenza A viruses in the last decade have legitimized fears of a long-predicted pandemic. We thus investigated the response to secondary infections with an engineered, but still highly virulent, H5N1 influenza A virus in the C57BL/6 mouse model. Mice primed with the H1N1 A/Puerto Rico/8/34 (PR8) virus were partially protected from lethality following respiratory infection with the modified H5N1 virus A/Vietnam/1203/04 (ΔVn1203). In contrast, those that had been comparably exposed to the HKx31 (H3N2) virus succumbed to the ΔVn1203 challenge, despite similarities in viral replication, weight loss, and secondary CD8+-T-cell response characteristics. All three viruses share the internal genes of PR8 that are known to stimulate protective CD8+-T-cell-mediated immunity. This differential survival of PR8- and HKx31-primed mice was also apparent for antibody-deficient mice challenged with the ΔVn1203 virus. The relative protection afforded by PR8 priming was abrogated in tumor necrosis factor-deficient (TNF−/−) mice, although lung fluids from the B6 HKx31-primed mice contained more TNF early after challenge. These data demonstrate that the nature of the primary infection can influence pathological outcomes following virulent influenza virus challenge, although the effect is not clearly correlated with classical measures of CD8+-T-cell-mediated immunity.

scholarly journals Consequences of Immunodominant Epitope Deletion for Minor Influenza Virus-Specific CD8+-T-Cell Responses

2005 ◽  
Vol 79 (7) ◽  
pp. 4329-4339 ◽  
Author(s):  
Samita S. Andreansky ◽  
John Stambas ◽  
Paul G. Thomas ◽  
Weidong Xie ◽  
Richard J. Webby ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Influenza A ◽  
Reverse Genetics ◽  
H3n2 Virus ◽  
Influenza A Viruses ◽  
Cell Responses ◽  
Infected Cells ◽  
H3n2 Influenza

ABSTRACT The extent to which CD8+ T cells specific for other antigens expand to compensate for the mutational loss of the prominent DbNP366 and DbPA224 epitopes has been investigated using H1N1 and H3N2 influenza A viruses modified by reverse genetics. Significantly increased numbers of CD8+ KbPB1703 +, CD8+ KbNS2114 +, and CD8+ DbPB1-F262 + T cells were found in the spleen and in the inflammatory population recovered by bronchoalveolar lavage from mice that were first given the −NP−PA H1N1 virus intraperitoneally and then challenged intranasally with the homologous H3N2 virus. The effect was less consistent when this prime-boost protocol was reversed. Also, though the quality of the response measured by cytokine staining showed some evidence of modification when these minor CD8+-T-cell populations were forced to play a more prominent part, the effects were relatively small and no consistent pattern emerged. The magnitude of the enhanced clonal expansion following secondary challenge suggested that the prime-boost with the −NP−PA viruses gave a response overall that was little different in magnitude from that following comparable exposure to the unmanipulated viruses. This was indeed shown to be the case when the total response was measured by ELISPOT analysis with virus-infected cells as stimulators. More surprisingly, the same effect was seen following primary challenge, though individual analysis of the CD8+ KbPB1703 +, CD8+ KbNS2114 +, and CD8+ DbPB1-F262 + sets gave no indication of compensatory expansion. A possible explanation is that novel, as yet undetected epitopes emerge following primary exposure to the −NP−PA deletion viruses. These findings have implications for both natural infections and vaccines.

scholarly journals Stochastic processes dominate the within and between host evolution of influenza virus

2017 ◽  
Author(s):  
John T. McCrone ◽  
Robert J. Woods ◽  
Emily T. Martin ◽  
Ryan E. Malosh ◽  
Arnold S. Monto ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Stochastic Processes ◽  
Influenza A ◽  
Evolutionary Dynamics ◽  
Sequence Data ◽  
Influenza A Viruses ◽  
Effective Population ◽  
The Individual ◽  
Host Evolution

AbstractThe global evolutionary dynamics of influenza virus ultimately derive from processes that take place within and between infected individuals. Here we define the dynamics of influenza A virus populations in human hosts through next generation sequencing of 249 specimens from 200 individuals collected over 6290 person-seasons of observation. Because these viruses were collected over 5 seasons from individuals in a prospective community-based cohort, they are broadly representative of natural human infections with seasonal viruses. We used viral sequence data from 35 serially sampled individuals to estimate a within host effective population size of 30-70 and an in vivo mutation rate of 4x10−5 per nucleotide per cellular infectious cycle. These estimates are consistent across several models and robust to the models' underlying assumptions. We also identified 43 epidemiologically linked and genetically validated transmission pairs. Maximum likelihood optimization of multiple transmission models estimates an effective transmission bottleneck of 1-2 distinct genomes. Our data suggest that positive selection of novel viral variants is inefficient at the level of the individual host and that genetic drift and other stochastic processes dominate the within and between host evolution of influenza A viruses.

scholarly journals Phylogeographic reconstruction using air transportation data and its application to the 2009 H1N1 influenza A pandemic

2019 ◽  
Author(s):  
Susanne Reimering ◽  
Sebastian Muñoz ◽  
Alice C. McHardy
Keyword(s):  
Influenza A ◽  
State Of The Art ◽  
Sequence Data ◽  
Air Transportation ◽  
H1n1 Influenza ◽  
Real Sequence ◽  
Influenza A Viruses ◽  
Geographic Spread ◽  
2009 H1n1 ◽  
Genetic Sequences

AbstractInfluenza A viruses cause seasonal epidemics and occasional pandemics in the human population. While the worldwide circulation of seasonal influenza is at least partly understood, the exact migration patterns between countries, states or cities are not well studied. Here, we use the Sankoff algorithm for parsimonious phylogeographic reconstruction together with effective distances based on a worldwide air transportation network. By first simulating geographic spread and then phylogenetic trees and genetic sequences, we confirmed that reconstructions with effective distances inferred phylogeographic spread more accurately than reconstructions with geographic distances and Bayesian reconstructions with BEAST, the current state-of-the-art. Our method extends the state-of-the-art by using fine-grained locations like airports and inferring intermediate locations not observed among sampled isolates. When applied to sequence data of the pandemic H1N1 influenza A virus in 2009, our approach correctly inferred the origin and proposed airports mainly involved in the spread of the virus. In case of a novel outbreak, this approach allows to rapidly analyze sequence data and infer origin and spread routes to improve disease surveillance and control.Author summaryInfluenza A viruses infect up to 5 million people in recurring epidemics every year. Further, viruses of zoonotic origin constantly pose a pandemic risk. Understanding the geographical spread of these viruses, including the origin and the main spread routes between cities, states or countries, could help to monitor or contain novel outbreaks. Based on genetic sequences and sampling locations, the geographic spread can be reconstructed along a phylogenetic tree. Our approach uses a parsimonious reconstruction with air transportation data and was verified using a simulation of the 2009 H1N1 influenza A pandemic. Applied to real sequence data of the outbreak, our analysis gave detailed insights into spread patterns of influenza A viruses, highlighting the origin as well as airports mainly involved in the spread.

scholarly journals Method comparison of targeted influenza A virus typing and whole-genome sequencing from respiratory specimens of companion animals

2020 ◽  
pp. 104063872093387
Author(s):  
Patrick K. Mitchell ◽  
Brittany D. Cronk ◽  
Ian E. H. Voorhees ◽  
Derek Rothenheber ◽  
Renee R. Anderson ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Influenza A ◽  
Sequence Data ◽  
Companion Animals ◽  
The United States ◽  
Quality Data ◽  
Whole Genome ◽  
Influenza A Viruses ◽  
Respiratory Specimens

Epidemics of H3N8 and H3N2 influenza A viruses (IAVs) in dogs, along with recognition of spillover infections from IAV strains typically found in humans or other animals, have emphasized the importance of efficient laboratory testing. Given the lack of active IAV surveillance or immunization requirements for dogs, cats, or horses imported into the United States, serotype prediction and whole-genome sequencing of positive specimens detected at veterinary diagnostic laboratories are also needed. The conserved sequences at the ends of the viral genome segments facilitate universal amplification of all segments of viral genomes directly from respiratory specimens. Although several methods for genomic analysis have been reported, no optimization focusing on companion animal strains has been described, to our knowledge. We compared 2 sets of published universal amplification primers using 26 IAV-positive specimens from dogs, horses, and a cat. Libraries prepared from the resulting amplicons were sequenced using Illumina chemistry, and reference-based assemblies were generated from the data produced by both methods. Although both methods produced high-quality data, coverage profiles and base calling differed between the 2 methods. The sequence data were also used to identify the subtype of the IAV strains sequenced and then compared to standard PCR assays for neuraminidase types N2 and N8.

scholarly journals Prevalence of antibody against influenza A viruses in the Kren-Akorore, an Indian tribe of Central Brazil, first contacted in 1973

1985 ◽  
Vol 95 (1) ◽  
pp. 159-164 ◽  
Author(s):  
J. P. Nascimento ◽  
M. M. Krawczuk ◽  
L. F. Marcopito ◽  
R. G. Baruzzi
Keyword(s):  
Hong Kong ◽  
Influenza A ◽  
H3n2 Virus ◽  
Influenza A Viruses ◽  
Serum Samples ◽  
Urban Populations ◽  
Indian Populations ◽  
Central Brazil ◽  
Indian Tribe ◽  
Civilized World

SUMMARYInfluenza A antibodies in serum samples obtained in 1980 from two Indian populations in Central Brazil were compared. The Kren-Akorore, who were first contacted in 1973 and two years later transferred to the Xingu Indian Park (PIX), were compared with Indians from other tribes already living in the PIX before 1975. An analysis was made of the prevalence and distribution of antibodies against the influenza A viruses which have circulated in the civilized world since 1918. Antibodies to the early influenza A viruses were absent in both Indian populations, but A/Hong Kong/1/68 (H3N2) virus apparently circulated in the PIX. No antibody to influenza A/Bangkok/I/79 or to A/Brazil/11/78 (H1N1) was found in any of the sera, whereas antibodies to these viruses were commonly found in urban populations in Brazil. The evidence from influenza antibodies agrees with the information that the Kren-Akorore Indians had been living in complete isolation until 1973, when they were first contacted.

scholarly journals Adaptation of Pandemic H2N2 Influenza A Viruses in Humans

2014 ◽  
Vol 89 (4) ◽  
pp. 2442-2447 ◽  
Author(s):  
Udayan Joseph ◽  
Martin Linster ◽  
Yuka Suzuki ◽  
Scott Krauss ◽  
Rebecca A. Halpin ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Influenza A ◽  
Avian Species ◽  
Influenza A Viruses ◽  
Genetic Sequences ◽  
H2n2 Virus ◽  
Virus Genomes ◽  
Virus Isolates

The 1957 A/H2N2 influenza virus caused an estimated 2 million fatalities during the pandemic. Since viruses of the H2 subtype continue to infect avian species and pigs, the threat of reintroduction into humans remains. To determine factors involved in the zoonotic origin of the 1957 pandemic, we performed analyses on genetic sequences of 175 newly sequenced human and avian H2N2 virus isolates and all publicly available influenza virus genomes.

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