scholarly journals Pigs with Severe Combined Immunodeficiency Are Impaired in Controlling Influenza A Virus Infection

2016 ◽  
Vol 9 (2) ◽  
pp. 193-202 ◽  
Author(s):  
Daniela S. Rajao ◽  
Crystal L. Loving ◽  
Emily H. Waide ◽  
Phillip C. Gauger ◽  
Jack C.M. Dekkers ◽  
...  
Keyword(s):  
Nk Cells ◽  
Influenza A ◽  
Severe Combined Immunodeficiency ◽  
Lung Pathology ◽  
Combined Immunodeficiency ◽  
Influenza A Viruses ◽  
Nasal Swabs ◽  
2009 H1n1 ◽  
Pulmonary Pathology ◽  
Viral Titers

Influenza A viruses (IAV) infect many host species, including humans and pigs. Severe combined immunodeficiency (SCID) is a condition characterized by a deficiency of T, B, and/or natural killer (NK) cells. Animal models of SCID have great value for biomedical research. Here, we evaluated the pathogenesis and the innate immune response to the 2009 H1N1 pandemic IAV (H1N1pdm09) using a recently identified line of naturally occurring SCID pigs deficient in T and B lymphocytes that still have functional NK cells. SCID pigs challenged with H1N1pdm09 showed milder lung pathology compared to the non-SCID heterozygous carrier pigs. Viral titers in the lungs and nasal swabs of challenged SCID pigs were significantly higher than in carrier pigs 7 days postinfection, despite higher levels of IL-1β and IFN-α in the lungs of SCID pigs. The lower levels of pulmonary pathology were associated with the T and B cell absence in response to infection. The higher viral titers, prolonged shedding, and delayed viral clearance indicated that innate immunity was insufficient for controlling IAV in pigs. This recently identified line of SCID pigs provides a valuable model to understand the immune mechanisms associated with influenza protection and recovery in a natural host.

scholarly journals Assessment of exposure to influenza A viruses in pigs between weaning and market age

2021 ◽  
Vol 52 (1) ◽  
Author(s):  
Juliana Bonin Ferreira ◽  
Zvonimir Poljak ◽  
Robert Friendship ◽  
Éva Nagy ◽  
Greg Wideman ◽  
...  
Keyword(s):  
Influenza A ◽  
Production Systems ◽  
Influenza A Viruses ◽  
Ha Gene ◽  
Testing Strategies ◽  
Common Causes ◽  
Nasal Swabs ◽  
Antibody Titers ◽  
2009 H1n1 ◽  
Low Prevalence

AbstractInfluenza A viruses (IAVs) are common causes of respiratory infection in pigs. The objective of this study was to characterize the circulation of IAVs between weaning and market age on the basis of development of antibody response and molecular epidemiology of detected viruses. Two batches of weaned pigs were followed in the nursery and finisher barns with a sample of 81 and 75 pigs. Nasal swabs and blood samples were collected from individual pigs for virological and serological analyses. A H3N2 subtype virus, of cluster IV, was detected in Study 1, with a maximum of 97.9% identity to HA gene of viruses previously isolated in Ontario. In Study 2, a H1N1 subtype virus, of 2009 H1N1 pandemic lineage, was detected, with a maximum of 97.8% identity to HA gene of viruses previously isolated in Ontario. On the basis of HA gene, it was observed that pigs were being detected with the same virus over time. The existence of antibody titers for IAV other than the isolated one confirmed that more than one subtype can circulate in the same population. In Study 1, pigs with higher numbers of IAV detection had lower serological titers for the same virus that was confirmed to circulate in the nursery (P < 0.01). Thorough knowledge of all endemic viral strains is fundamental for development of infection and disease control, particularly in complex production systems. This may include consideration of sampling and testing strategies which could detect circulation of all IAV variants, even if they have low prevalence.

scholarly journals Natural killer (NK) cell response to virus infections in mice with severe combined immunodeficiency. The stimulation of NK cells and the NK cell-dependent control of virus infections occur independently of T and B cell function.

1991 ◽  
Vol 173 (5) ◽  
pp. 1053-1063 ◽  
Author(s):  
R M Welsh ◽  
J O Brubaker ◽  
M Vargas-Cortes ◽  
C L O'Donnell
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Cell Response ◽  
Nk Cell ◽  
Severe Combined Immunodeficiency ◽  
Scid Mice ◽  
Combined Immunodeficiency ◽  
Virus Infections ◽  
Mcmv Infection

The activation, proliferation, and antiviral properties of natural killer (NK) cells were examined in severe combined immunodeficiency (SCID) mice to determine the influence of mature T or B cells on virus-induced NK cell functions and to more conclusively determine the antiviral properties of prototypical CD3- NK cells. NK cells were activated to high levels of cytotoxicity 3 d after infection of mice with lymphocytic choriomeningitis virus (LCMV) or murine cytomegalovirus (MCMV). Analyses of spleen leukocytes from LCMV-infected mice by a variety of techniques indicated that the NK cells proliferated and increased in number during infection. Propidium iodide staining of the DNA of cycling cells revealed that the great majority of proliferating spleen leukocytes 3 d after LCMV infection was of the NK cell phenotype (CD3-, Ig-, Mac-1+, CZ1+, 50% Thy-1+), in contrast to uninfected mice, whose proliferating cells were predominantly of other lineages. Analyses of the NK cell responses over a 2 wk period in control CB17 mice infected with MCMV indicated a sharp rise in serum interferon (IFN) and spleen NK cell activity early (days 3-5) in infection, followed by sharp declines at later stages. In SCID mice the IFN levels continued to rise over a 10-d period, whereas the NK cell response peaked on day 3-5 and gradually tapered. In contrast to the immunocompetent CB17 mice, SCID mice did not clear the MCMV infection and eventually succumbed. SCID mice, again in contrast to immunocompetent CB17 mice, also failed to clear infections with LCMV and Pichinde virus (PV); these mice, infected as adults, did not die but instead developed long-term persistent infections. Depletion of the NK cells in vivo with antiserum to asialo GM1 rendered both SCID and CB17 control mice much more sensitive to MCMV infection, as shown by titers of virus in organs and by survival curves. In contrast, similar depletions of NK cells did not enhance the titers of the NK cell-resistant virus, LCMV. Two variants of PV, one sensitive to NK cells and the other selected for resistance to NK cells by in vivo passage, were also tested in NK cell-depleted SCID mice. The NK-sensitive PV replicated to higher titers in NK cell-depleted SCID mice, whereas the titers of the NK cell-resistant PV were the same, whether or not the mice had NK cells. These experiments support the concept that CD3- prototypical NK cells mediate resistance to NK cell-sensitive viruses via a mechanism independent of antiviral or "natural" antibody.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Strain-dependent effects of PB1-F2 of triple-reassortant H3N2 influenza viruses in swine

2012 ◽  
Vol 93 (10) ◽  
pp. 2204-2214 ◽  
Author(s):  
Lindomar Pena ◽  
Amy L. Vincent ◽  
Crystal L. Loving ◽  
Jamie N. Henningson ◽  
Kelly M. Lager ◽  
...  
Keyword(s):  
Virus Replication ◽  
Influenza A ◽  
Reverse Genetics ◽  
Influenza Viruses ◽  
Dependent Manner ◽  
Lung Pathology ◽  
Influenza A Viruses ◽  
Virus Shedding ◽  
The Impact ◽  
Strain Dependent

The PB1-F2 protein of the influenza A viruses (IAVs) can act as a virulence factor in mice. Its contribution to the virulence of IAV in swine, however, remains largely unexplored. In this study, we chose two genetically related H3N2 triple-reassortant IAVs to assess the impact of PB1-F2 in virus replication and virulence in pigs. Using reverse genetics, we disrupted the PB1-F2 ORF of A/swine/Wisconsin/14094/99 (H3N2) (Sw/99) and A/turkey/Ohio/313053/04 (H3N2) (Ty/04). Removing the PB1-F2 ORF led to increased expression of PB1-N40 in a strain-dependent manner. Ablation of the PB1-F2 ORF (or incorporation of the N66S mutation in the PB1-F2 ORF, Sw/99 N66S) affected the replication in porcine alveolar macrophages of only the Sw/99 KO (PB1-F2 knockout) and Sw/99 N66S variants. The Ty/04 KO strain showed decreased virus replication in swine respiratory explants, whereas no such effect was observed in Sw/99 KO, compared with the wild-type (WT) counterparts. In pigs, PB1-F2 did not affect virus shedding or viral load in the lungs for any of these strains. Upon necropsy, PB1-F2 had no effect on the lung pathology caused by Sw/99 variants. Interestingly, the Ty/04 KO-infected pigs showed significantly increased lung pathology at 3 days post-infection compared with pigs infected with the Ty/04 WT strain. In addition, the pulmonary levels of interleukin (IL)-6, IL-8 and gamma interferon were regulated differentially by the expression of PB1-F2. Taken together, these results indicate that PB1-F2 modulates virus replication, virulence and innate immune responses in pigs in a strain-dependent fashion.

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 Molecular Evidence of Influenza A Virus Circulation in African Dromedary Camels Imported to Saudi Arabia, 2017–2018

2019 ◽  
Vol 6 (10) ◽  
Author(s):  
Abdulaziz Alghamdi ◽  
Ahmed M Hassan ◽  
Ahmed M Tolah ◽  
Sawsan S Alamari ◽  
Abdulrahman A Alzahrani ◽  
...  
Keyword(s):  
Saudi Arabia ◽  
Influenza A ◽  
Swine Influenza ◽  
Interspecies Transmission ◽  
Molecular Evidence ◽  
Influenza A Viruses ◽  
Influenza A H1n1 ◽  
Nasal Swabs ◽  
Close Relationship ◽  
Partial Genome

Abstract Little is known about influenza A viruses in dromedaries. Here, we detected influenza A viral RNA in 11 specimens (1.7 %) out of 665 nasal swabs collected from dromedaries between 2017 and 2018 in Saudi Arabia. Positive samples were detected only in imported camels from Sudan and Djibouti but not local ones. Partial genome sequencing indicates a close relationship to 2009–2019 human/swine influenza A H1N1 isolates from different countries, suggesting possible interspecies transmission. Taken together, dromedaries could represent a potentially unrecognized permissive host for these viruses, highlighting the need for enhanced surveillance in animals to aid implementation of one-health strategies.

Detection of T lymphocytes with a second-site mutation in skin lesions of atypical X-linked severe combined immunodeficiency mimicking Omenn syndrome

Blood ◽  
2008 ◽  
Vol 112 (5) ◽  
pp. 1872-1875 ◽  
Author(s):  
Taizo Wada ◽  
Masahiro Yasui ◽  
Tomoko Toma ◽  
Yuko Nakayama ◽  
Mika Nishida ◽  
...  
Keyword(s):  
T Cells ◽  
Nk Cells ◽  
Severe Combined Immunodeficiency ◽  
Phenotypic Expression ◽  
Splice Site Mutation ◽  
Skin Lesions ◽  
Omenn Syndrome ◽  
Combined Immunodeficiency ◽  
Site Mutation ◽  
Gamma Chain

Abstract X-linked severe combined immunodeficiency (XSCID) is caused by mutations of the common gamma chain (γc) and usually characterized by the absence of T and natural killer (NK) cells. Here, we report an atypical case of XSCID presenting with autologous T and NK cells and Omenn syndrome-like manifestations. The patient carried a splice-site mutation (IVS1+5G>A) that caused most of the mRNA to be incorrectly spliced but produced normally spliced transcript in lesser amount, leading to residual γc expression and development of T and NK cells. The skin biopsy specimen showed massive infiltration of revertant T cells. Those T cells were found to have a second-site mutation and result in complete restoration of correct splicing. These findings suggest that the clinical spectrum of XSCID is quite broad and includes atypical cases mimicking Omenn syndrome, and highlight the importance of revertant mosaicism as a possible cause for variable phenotypic expression.

scholarly journals Characterization of Oseltamivir-Resistant 2009 H1N1 Pandemic Influenza A Viruses

2010 ◽  
Vol 6 (8) ◽  
pp. e1001079 ◽  
Author(s):  
Maki Kiso ◽  
Kyoko Shinya ◽  
Masayuki Shimojima ◽  
Ryo Takano ◽  
Kei Takahashi ◽  
...  
Keyword(s):  
Pandemic Influenza ◽  
Influenza A ◽  
H1n1 Pandemic ◽  
Influenza A Viruses ◽  
2009 H1n1
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