This service exclusively searches for literature that cites resources. Please be aware that the total number of searchable documents is limited to those containing RRIDs and does not include all open-access literature.
PA-X protein arises from a ribosomal frameshift in the PA of influenza A virus (IAV). However, the immune regulatory effect of the PA-X protein of H1N1 viruses on the nasal mucosal system remains unclear. Here, a PA-X deficient H1N1 rPR8 viral strain (rPR8-△PAX) was generated and its pathogenicity was determined. The results showed that PA-X was a pro-virulence factor in mice. Furthermore, it reduced the ability of H1N1 viruses to infect dendritic cells (DCs), the regulator of the mucosal immune system, but not non-immune cells (DF-1 and Calu-3). Following intranasal infection of mice, CCL20, a chemokine that monitors the recruitment of submucosal DCs, was downregulated by PA-X, resulting in an inhibition of the recruitment of CD11b+ DCs to submucosa. It also attenuated the migration of CCR7+ DCs to cervical lymph nodes and inhibited DC maturation with low MHC II and CD40 expression. Moreover, PA-X suppressed the maturation of phenotypic markers (CD80, CD86, CD40, and MHC II) and the levels of secreted pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) while enhancing endocytosis and levels of anti-inflammatory IL-10 in vitro, suggesting an impaired maturation of DCs that the key step for the activation of downstream immune responses. These findings suggested that the PA-X protein played a critical role in escaping the immune response of nasal mucosal DCs for increasing the virulence of H1N1 viruses.
Inbred mice have several advantages, including genetic similarity to humans, a well-established gene manipulation system, and strong tolerance to inbreeding. However, inbred mice derived from a limited genetic pool have a small genetic diversity. Thus, the development of new inbred strains from wild mice is needed to overcome this limitation. Hence, in this study, we used a new strain of inbred mice called KWM/Hym. We sequenced the Mx1 gene to elucidate the genetic diversities of KWM/Hym mice and observed the biological alterations of the Mx1 protein upon influenza A infection.
To determine if fatal infections caused by different highly virulent influenza A viruses share the same pathogenesis, we compared 2 different influenza A virus subtypes, H1N1 and H5N1. The subtypes, which had shown no pathogenicity in laboratory mice, were forced to evolve by serial passaging. Although both adapted viruses evoked diffuse alveolar damage and showed a similar 50% mouse lethal dose and the same peak lung concentration, each had a distinct pathologic signature and caused a different course of acute respiratory distress syndrome. In the absence of any virus labeling, a histologist could readily distinguish infections caused by these 2 viruses. The different histologic features described in this study here refute the hypothesis of a single, universal cytokine storm underlying all fatal influenza diseases. Research is thus crucially needed to identify sets of virulence markers and to examine whether treatment should be tailored to the influenza virus pathotype.
Influenza A viruses circulating in pigs in Brazil are still not characterized, and only limited data are available about swine influenza epidemiology in the country. Therefore, we characterized the hemagglutinin (HA) and neuraminidase (NA) genes of influenza viruses isolated from Brazilian pigs. We also evaluated one case of probable swine-to-human transmission.
In April 2009, a novel triple-reassortant swine influenza A H1N1 virus ("A/H1N1pdm"; also known as SOIV) was detected and spread globally as the first influenza pandemic of the 21(st) century. Sequencing has since been conducted at an unprecedented rate globally in order to monitor the diversification of this emergent virus and to track mutations that may affect virus behavior.
H1N1 subtype influenza A viruses are the most common type of influenza A virus to infect humans. The two major outbreaks of the virus in 1918 and 2009 had a great impact both on human health and social development. Though data on their complete genome sequences have recently been obtained, the evolution and mutation of A/H1N1 viruses remain unknown to this day. Among many drivers, the impact of environmental factors on mutation is a novel hypothesis worth studying. Here, a geographically disaggregated method was used to explore the relationship between environmental factors and mutation of A/H1N1 viruses from 2000-2019. All of the 11,721 geo-located cases were examined and the data was analysed of six environmental elements according to the time and location (latitude and longitude) of those cases. The main mutation value was obtained by comparing the sequence of the influenza virus strain with the earliest reported sequence. It was found that environmental factors systematically affect the mutation of A/H1N1 viruses. Minimum temperature displayed a nonlinear, rising association with mutation, with a maximum ~15 °C. The effects of precipitation and social development index (nighttime light) were more complex, while population density was linearly and positively correlated with mutation of A/H1N1 viruses. Our results provide novel insight into understanding the complex relationships between mutation of A/H1N1 viruses and environmental factors.
Influenza A virus infects various animal species and transmits among different hosts, especially between humans and swine. Swine may serve as a mixing vessel to create new reassortants that could infect humans. Thus, monitoring and characterizing influenza viruses in swine are important in preventing interspecies transmission. We report the emergence and characterization of a novel H3N1 subtype of swine influenza virus (SIV) in the United States. Phylogenetic analysis showed that the H3N1 SIVs may have acquired the hemagglutinin gene from an H3N2 turkey isolate, the neuraminidase gene from a human H1N1 isolate, and the remaining genes from currently circulating SIVs. The H3N1 SIVs were antigenically related to the turkey virus. Lung lesions and nasal shedding occurred in swine infected with the H3N1 SIVs, suggesting the potential to transmit among swine and to humans. Further surveillance will help determine whether this novel subtype will continue to circulate in swine populations.
Influenza A viruses cause highly contagious diseases in a variety of hosts, including humans and pigs. To develop a vaccine that can be broadly effective against genetically divergent strains of the virus, in this study we employed molecular breeding (DNA shuffling) technology to create a panel of chimeric HA genes.
Swine influenza virus (SIV) and Mycoplasma hyopneumoniae (Mhp) are widespread in farms and are major pathogens involved in the porcine respiratory disease complex (PRDC). The aim of this experiment was to compare the pathogenicity of European avian-like swine H1N1 and European human-like reassortant swine H1N2 viruses in naïve pigs and in pigs previously infected with Mhp. Six groups of SPF pigs were inoculated intra-tracheally with either Mhp, or H1N1, or H1N2 or Mhp+H1N1 or Mhp+H1N2, both pathogens being inoculated at 21 days intervals in these two last groups. A mock-infected group was included. Although both SIV strains induced clinical signs when singly inoculated, results indicated that the H1N2 SIV was more pathogenic than the H1N1 virus, with an earlier shedding and a greater spread in lungs. Initial infection with Mhp before SIV inoculation increased flu clinical signs and pathogenesis (hyperthermia, loss of appetite, pneumonia lesions) due to the H1N1 virus but did not modify significantly outcomes of H1N2 infection. Thus, Mhp and SIV H1N1 appeared to act synergistically, whereas Mhp and SIV H1N2 would compete, as H1N2 infection led to the elimination of Mhp in lung diaphragmatic lobes. In conclusion, SIV would be a risk factor for the severity of respiratory disorders when associated with Mhp, depending on the viral subtype involved. This experimental model of coinfection with Mhp and avian-like swine H1N1 is a relevant tool for studying the pathogenesis of SIV-associated PRDC and testing intervention strategies for the control of the disease.
After the occurrence of 2009 pandemic H1N1, close attention has been paid to the H1N1 subtype swine influenza viruses (H1N1 SIV) by scientific communities in many countries. A large-scale sequence analysis of the NCBI Influenza Virus Resource Database on H1N1 SIVs submitted primarily by scientists in China during 1992 to 2011 was performed. The aims of this study were to elucidate the genetic and evolutionary characteristics of H1N1 SIVs, to identify and unify the lineages and genetic characteristics of the H1N1 SIVs isolated in mainland China.
Reporter influenza A viruses (IAVs) carrying fluorescent or luminescent genes provide a powerful tool for both basic and translational research. Most reporter IAVs are based on the backbone of either subtype H1N1 viruses, A/Puerto Rico/8/1934 (PR8) or A/WSN/1933, but no reporter subtype H3N2 virus is currently available to our knowledge. Since the IAV subtype H3N2 co-circulates with H1N1 among humans causing annual epidemics, a reporter influenza A subtype H3N2 virus would be highly valuable. In this study, the segments of A/Wyoming/3/03 (NY, H3N2) virus encoding hemagglutinin and neuraminidase, respectively, were reassorted with the six internal genes of PR8 where the NS gene was fused with a Gaussia luciferase (Gluc) gene. Using reverse genetics, NY-r19-Gluc, a replication competent reassortant influenza A subtype H3N2 virus expressing reporter Gluc was successfully generated. This reporter virus is stable during replication in Madin-Darby canine kidney (MDCK) cells, and preliminary studies demonstrated it as a useful tool to evaluate antivirals. In addition, NY-r19-Gluc virus will be a powerful tool in other studies including the application of diagnostic and therapeutic antibodies as well as the evaluation of novel vaccines.
Highly pathogenic avian influenza virus subtype H5N1 infects humans with a high fatality rate and has pandemic potential. Vaccination is the preferred approach for prevention of H5N1 infection. Seasonal influenza virus infection has been reported to provide heterosubtypic immunity against influenza A virus infection to some extend. In this study, we used a mouse model pre-exposed to an H1N1 influenza virus and evaluated the protective ability provided by a single dose of DNA vaccines encoding conserved H5N1 proteins.
A novel swine-origin pandemic influenza A(H1N1) virus (H1N1pdm, also referred to as S-OIV) was identified as the causative agent of the 21(st) century's first influenza pandemic, but molecular features conferring its ability of human-to-human transmission has not been identified. Here we compared the protein sequences of 2009 H1N1pdm strains with those causing other pandemics and the viruses isolated from humans, swines and avians, and then analyzed the mutation trend of the residues at the signature and non-signature positions, which are species- and non-species-associated, respectively, in the proteins of H1N1pdm during the pandemic of 2009. We confirmed that the host-specific genomic signatures of 2009 H1N1pdm, which are mainly swine-like, were highly identical to those of the 1918 H1N1pdm. During the short period of time when the pandemic alert level was raised from phase 4 to phase 6, one signature residue at the position of NP-100 mutated from valine to isoleucine. Four non-signature residues, at positions NA-91, NA-233, HA-206, and NS1-123, also changed during the epidemic in 2009. All these mutant residues, except that at NA-91, are located in the viral functional domains, suggesting that they may play roles in the human adaption and virulence of 2009 H1N1pdm.
The pandemic influenza virus (2009 H1N1) was recently introduced into the human population. The hemagglutinin (HA) gene of 2009 H1N1 is derived from "classical swine H1N1" virus, which likely shares a common ancestor with the human H1N1 virus that caused the pandemic in 1918, whose descendant viruses are still circulating in the human population with highly altered antigenicity of HA. However, information on the structural basis to compare the HA antigenicity among 2009 H1N1, the 1918 pandemic, and seasonal human H1N1 viruses has been lacking. By homology modeling of the HA structure, here we show that HAs of 2009 H1N1 and the 1918 pandemic virus share a significant number of amino acid residues in known antigenic sites, suggesting the existence of common epitopes for neutralizing antibodies cross-reactive to both HAs. It was noted that the early human H1N1 viruses isolated in the 1930s-1940s still harbored some of the original epitopes that are also found in 2009 H1N1. Interestingly, while 2009 H1N1 HA lacks the multiple N-glycosylations that have been found to be associated with an antigenic change of the human H1N1 virus during the early epidemic of this virus, 2009 H1N1 HA still retains unique three-codon motifs, some of which became N-glycosylation sites via a single nucleotide mutation in the human H1N1 virus. We thus hypothesize that the 2009 H1N1 HA antigenic sites involving the conserved amino acids will soon be targeted by antibody-mediated selection pressure in humans. Indeed, amino acid substitutions predicted here are occurring in the recent 2009 H1N1 variants. The present study suggests that antibodies elicited by natural infection with the 1918 pandemic or its early descendant viruses play a role in specific immunity against 2009 H1N1, and provides an insight into future likely antigenic changes in the evolutionary process of 2009 H1N1 in the human population.
Reassortment between human and avian influenza viruses (AIV) may result in novel viruses with new characteristics that may threaten human health when causing the next flu pandemic. A particular risk may be posed by avian influenza viruses of subtype H9N2 that are currently massively circulating in domestic poultry in Asia and have been shown to infect humans. In this study, we investigate the characteristics and compatibility of a human H1N1 virus with avian H9N2 derived genes.
The swine influenza (SI) is an infectious disease of swine and human. The novel swine-origin influenza A (H1N1) that emerged from April 2009 in Mexico spread rapidly and caused a human pandemic globally. To determine whether the tremendous virus had existed in or transmitted to pigs in southern China, eight H1N1 influenza strains were identified from pigs of Guangdong province during 2008-2009.
The pandemic influenza A (H1N1) 2009 virus (pH1N1) contains novel gene segments of zoonotic origin that lack virulence and antiviral resistance markers. We aimed to evaluate the applicability and accuracy of mass spectrometry-based comparative sequence analysis (MSCSA) to detect genetic mutations associated with increased virulence or antiviral resistance in pH1N1. During the 2009 H1N1 pandemic, routine surveillance specimens and clinical antiviral resistance monitoring specimens were analyzed. Routine surveillance specimens obtained from 70 patients with pH1N1 infection were evaluated for mutations associated with increased virulence (PB1-F2, PB2 and NS1 genes) or antiviral resistance (neuraminidase gene, NA) using MSCSA and Sanger sequencing. MSCSA and Sanger sequencing results revealed a high concordance (nucleotides >99%, SNPs ∼ 94%). Virulence or resistance markers were not detected in routine surveillance specimens: all identified SNPs encoded for silent mutations or non-relevant amino acid substitutions. In a second study population, the presence of H275Y oseltamivir resistant virus was identified by real-time PCR in 19 of 35 clinical antiviral resistance monitoring specimens obtained from 4 immunocompromised patients with ≥ 14 days prolonged pH1N1 excretion. MSCSA detected H275Y in 24% (4/19) of positive specimens and Sanger sequencing in 89% (17/19). MSCSA only detected H275Y when the mutation was dominant in the analyzed specimens. In conclusion, MSCSA may be used as a rapid screening tool during molecular surveillance of pH1N1. The low sensitivity for the detection of H275Y mutation in mixed viral populations suggests that MSCSA is not suitable for antiviral resistance monitoring in the clinical setting.
H11 subtype influenza viruses were isolated from a wide range of bird species and one strain also was isolated from swine. In an effort to generate reagents for a chimeric H11/1 hemagglutinin-based universal influenza virus vaccine candidate, we produced 28 monoclonal antibodies that recognize the H11 HA subtype. Here we characterized these antibodies in terms of binding breadth and functionality. We found that the antibodies bind broadly to North American and Eurasian lineage isolates and also show broad neutralizing activity, suggesting that immunogenic epitopes on the H11 head domain are not under strong pressure from immunity in the natural reservoir. Furthermore, we found that the antibodies were highly hemagglutination inhibition active against the homologous chimeric H11/1N1 virus, but approximately 50% lost this activity when tested against a virus expressing the same the full length H11 HA of which the head domain is present on cH11/1 HA. Furthermore, while strong neutralizing activity was found to a genetically distant North American lineage H11 isolate, little hemagglutination inhibition activity was detected. This suggests that small structural changes between wild type H11 and cH11/1 as well as between Eurasian and North American lineage H11 HAs can strongly influence the functionality of the isolated monoclonal antibodies.
Commercial swine farms provide unique systems for interspecies transmission of influenza A viruses (FLUAVs) at the animal-human interface. Bidirectional transmission of FLUAVs between pigs and humans plays a significant role in the generation of novel strains that become established in the new host population. Active FLUAV surveillance was conducted for 2 years on a commercial pig farm in Southern Guatemala with no history of FLUAV vaccination. Nasal swabs (n = 2,094) from fattening pigs (6 to 24 weeks old) with respiratory signs were collected weekly from May 2016 to February 2018. Swabs were screened for FLUAV by real-time reverse transcriptase PCR (RRT-PCR), and full virus genomes of FLUAV-positive swabs were sequenced by next-generation sequencing (NGS). FLUAV prevalence was 12.0% (95% confidence interval [CI], 10.6% to 13.4%) with two distinct periods of high infection. All samples were identified as FLUAVs of the H1N1 subtype within the H1 swine clade 1A.3.3.2 and whose ancestors are the human origin 2009 H1N1 influenza pandemic virus (H1N1 pdm09). Compared to the prototypic reference segment sequence, 10 amino acid signatures were observed on relevant antigenic sites on the hemagglutinin. The Guatemalan swine-origin FLUAVs show independent evolution from other H1N1 pdm09 FLUAVs circulating in Central America. The zoonotic risk of these viruses remains unknown but strongly calls for continued FLUAV surveillance in pigs in Guatemala. IMPORTANCE Despite increased surveillance efforts, the epidemiology of FLUAVs circulating in swine in Latin America remains understudied. For instance, the 2009 H1N1 influenza pandemic strain (H1N1 pdm09) emerged in Mexico, but its circulation remained undetected in pigs. In Central America, Guatemala is the country with the largest swine industry. We found a unique group of H1N1 pdm09 sequences that suggests independent evolution from similar viruses circulating in Central America. These viruses may represent the establishment of a novel genetic lineage with the potential to reassort with other cocirculating viruses and whose zoonotic risk remains to be determined.
Welcome to the FDI Lab - SciCrunch.org Resources search. From here you can search through a compilation of resources used by FDI Lab - SciCrunch.org and see how data is organized within our community.
You are currently on the Community Resources tab looking through categories and sources that FDI Lab - SciCrunch.org has compiled. You can navigate through those categories from here or change to a different tab to execute your search through. Each tab gives a different perspective on data.
If you have an account on FDI Lab - SciCrunch.org then you can log in from here to get additional features in FDI Lab - SciCrunch.org such as Collections, Saved Searches, and managing Resources.
Here is the search term that is being executed, you can type in anything you want to search for. Some tips to help searching:
You can save any searches you perform for quick access to later from here.
We recognized your search term and included synonyms and inferred terms along side your term to help get the data you are looking for.
If you are logged into FDI Lab - SciCrunch.org you can add data records to your collections to create custom spreadsheets across multiple sources of data.
Here are the facets that you can filter your papers by.
From here we'll present any options for the literature, such as exporting your current results.
If you have any further questions please check out our FAQs Page to ask questions and see our tutorials. Click this button to view this tutorial again.
Year:
Count: