scholarly journals Mutations in the NS1 Protein of Swine Influenza Virus Impair Anti-Interferon Activity and Confer Attenuation in Pigs

2005 ◽  
Vol 79 (12) ◽  
pp. 7535-7543 ◽  
Author(s):  
Alicia Solórzano ◽  
Richard J. Webby ◽  
Kelly M. Lager ◽  
Bruce H. Janke ◽  
Adolfo García-Sastre ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Nonstructural Protein ◽  
Swine Influenza Virus ◽  
Swine Influenza ◽  
Influenza Viruses ◽  
Model Systems ◽  
Ns1 Protein ◽  
Wild Type ◽  
Virulence Attenuation

ABSTRACT It has been shown previously that the nonstructural protein NS1 of influenza virus is an alpha/beta interferon (IFN-α/β) antagonist, both in vitro and in experimental animal model systems. However, evidence of this function in a natural host has not yet been obtained. Here we investigated the role of the NS1 protein in the virulence of a swine influenza virus (SIV) isolate in pigs by using reverse genetics. The virulent wild-type A/Swine/Texas/4199-2/98 (TX/98) virus and various mutants encoding carboxy-truncated NS1 proteins were rescued. Growth properties of TX/98 viruses with mutated NS1, induction of IFN in tissue culture, and virulence-attenuation in pigs were analyzed and compared to those of the recombinant wild-type TX/98 virus. Our results indicate that deletions in the NS1 protein decrease the ability of the TX/98 virus to prevent IFN-α/β synthesis in pig cells. Moreover, all NS1 mutant viruses were attenuated in pigs, and this correlated with the amount of IFN-α/β induced in vitro. These data suggest that the NS1 protein of SIV is a virulence factor. Due to their attenuation, NS1-mutated swine influenza viruses might have a great potential as live attenuated vaccine candidates against SIV infections of pigs.

scholarly journals Eurasian Avian-like M1 Plays More Important Role than M2 in Pathogenicity of 2009 Pandemic H1N1 Influenza Virus in Mice

Viruses ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2335
Author(s):  
Lixiang Xie ◽  
Guanlong Xu ◽  
Lingxiang Xin ◽  
Zhaofei Wang ◽  
Rujuan Wu ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Inflammatory Cytokines ◽  
Swine Influenza ◽  
Influenza Viruses ◽  
Chimeric Virus ◽  
Wild Type Virus ◽  
Type Virus ◽  
Wild Type ◽  
M Gene

Reassortant variant viruses generated between 2009 H1N1 pandemic influenza virus [A(H1N1)pdm09] and endemic swine influenza viruses posed a potential risk to humans. Surprisingly, genetic analysis showed that almost all of these variant viruses contained the M segment from A(H1N1)pdm09, which originated from Eurasian avian-like swine influenza viruses. Studies have shown that the A(H1N1)pdm09 M gene is critical for the transmissibility and pathogenicity of the variant viruses. However, the M gene encodes two proteins, M1 and M2, and which of those plays a more important role in virus pathogenicity remains unknown. In this study, the M1 and M2 genes of A(H1N1)pdm09 were replaced with those of endemic H3N2 swine influenza virus, respectively. The chimeric viruses were rescued and evaluated in vitro and in mice. Both M1 and M2 of H3N2 affected the virus replication in vitro. In mice, the introduction of H3N2 M1 attenuated the chimeric virus, where all the mice survived from the infection, compared with the wild type virus that caused 100 % mortality. However, the chimeric virus containing H3N2 M2 was still virulent to mice, and caused 16.6% mortality, as well as similar body weight loss to the wild type virus infected group. Compared with the wild type virus, the chimeric virus containing H3N2 M1 induced lower levels of inflammatory cytokines and higher levels of anti-inflammatory cytokines, whereas the chimeric virus containing H3N2 M2 induced substantial pro-inflammatory responses, but higher levels of anti-inflammatory cytokines. The study demonstrated that Eurasian avian-like M1 played a more important role than M2 in the pathogenicity of A(H1N1)pdm09 in mice.

scholarly journals Swine-Origin H1 Influenza Viruses Isolated from Humans Exhibit Sustained Infectivity in an Aerosol State

2019 ◽  
Vol 85 (10) ◽  
Author(s):  
Joanna A. Pulit-Penaloza ◽  
Jessica A. Belser ◽  
Terrence M. Tumpey ◽  
Taronna R. Maines
Keyword(s):  
Influenza Virus ◽  
Swine Influenza Virus ◽  
Virus Transmission ◽  
Swine Influenza ◽  
Influenza Viruses ◽  
Aerosol State ◽  
The Stability ◽  
Higher Doses ◽  
Enhanced Stability

ABSTRACT The relative importance of influenza virus transmission via aerosols is not fully understood, but experimental data suggest that aerosol transmission may represent a critical mode of influenza virus spread among humans. Decades ago, prototypical laboratory strains of influenza were shown to persist in aerosols; however, there is a paucity of data available covering currently circulating influenza viruses, which differ significantly from their predecessors. In this study, we evaluated the longevity of influenza viruses in aerosols generated in the laboratory. We selected a panel of H1 viruses that exhibit diverse transmission profiles in the ferret model, including four human isolates of swine origin (referred to as variant) and a seasonal strain. By measuring the ratio of viral RNA to infectious virus maintained in aerosols over time, we show that influenza viruses known to transmit efficiently through the air display enhanced stability in an aerosol state for prolonged periods compared to those viruses that do not transmit as efficiently. We then assessed whether H1 influenza virus was still capable of infecting and causing disease in ferrets after being aged in suspended aerosols. Ferrets exposed to very low levels of influenza virus (≤17 PFU) in aerosols aged for 15 or 30 min became infected, with five of six ferrets shedding virus in nasal washes at titers on par with ferrets who inhaled higher doses of unaged influenza virus. We describe here an underreported characteristic of influenza viruses, stability in aerosols, and make a direct connection to the role this characteristic plays in influenza transmission. IMPORTANCE Each time a swine influenza virus transmits to a human, it provides an opportunity for the virus to acquire adaptations needed for sustained human-to-human transmission. Here, we use aerobiology techniques to test the stability of swine-origin H1 subtype viruses in aerosols and evaluate their infectivity in ferrets. Our results show that highly transmissible influenza viruses display enhanced stability in an aerosol state compared to viruses that do not transmit as efficiently. Similar to human-adapted strains, swine-origin influenza viruses are infectious in ferrets at low doses even after prolonged suspension in the air. These data underscore the risk of airborne swine-origin influenza viruses and support the need for continued surveillance and refinement of innovative laboratory methods to investigate mammalian exposure to inhaled pathogens. Determination of the molecular markers that affect the longevity of airborne influenza viruses will improve our ability to quickly identify emerging strains that present the greatest threat to public health.

scholarly journals PB1-mediated virulence attenuation of H5N1 influenza virus in mice is associated with PB2

2011 ◽  
Vol 92 (6) ◽  
pp. 1435-1444 ◽  
Author(s):  
Jing Li ◽  
Yongqiang Li ◽  
Yi Hu ◽  
Guohui Chang ◽  
Wei Sun ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Recombinant Virus ◽  
Influenza Viruses ◽  
H5n1 Influenza Virus ◽  
Wild Type ◽  
Small Plaque ◽  
Large Plaque ◽  
H5n1 Influenza ◽  
Virulence Attenuation ◽  
N Terminus

H5N1 avian influenza viruses demonstrate different phenotypes, such as pathogenicity after one or serial passages in mammalian hosts or cells. To establish the molecular basis of these phenotypes, we cloned isolates from the lungs of mice infected with human A/Vietnam/1194/2004 (H5N1) influenza virus. Large-plaque isolates were less pathogenic to mice than small-plaque isolates. Genome sequencing revealed that the small-plaque and large-plaque isolates differed in several amino acids. In order to assess their effects on pathogenicity in mice, two amino acid changes common to attenuated isolates, one in PB2 (I63T) and the other in PB1 (T677M), were inserted into a wild-type recombinant virus construct. The PB2 (I63T) or PB1 (T677M) mutations alone did not alter the phenotype of H5N1 virus, whereas recombinant virus with both mutations was less pathogenic than the wild-type recombinant virus. Furthermore, the PB1 (T677M) mutation showed a lower replication efficiency, although it had higher polymerase activity. The recombinant virus with the PB2 (63T) mutation replicated as well as the wild-type recombinant virus. These results suggest that the C terminus of PB1 of H5N1 influenza virus mediates virulence attenuation of H5N1 influenza virus in mice, associating with the N terminus of PB2. However, the role of the N terminus of PB2 in virulence attenuation in mice remains unclear.

scholarly journals Effect of health seeking interval on outcome in swine flu cases attended a tertiary care hospital in southern Rajasthan region of India

2019 ◽  
Vol 6 (7) ◽  
pp. 2910
Author(s):  
Shalabh Sharma ◽  
Yogesh Kumar Singhal
Keyword(s):  
Influenza Virus ◽  
Clinical Care ◽  
Swine Influenza Virus ◽  
Swine Influenza ◽  
Influenza Viruses ◽  
Swine Flu ◽  
Care Hospital ◽  
Health Seeking ◽  
Early Presentation ◽  
Number Of Patients

Background: Swine flu influenza is an infection by H1N1 type of swine influenza virus. Swine influenza virus or swine-origin influenza virus (SIV or S-OIV) is a strain of the family of influenza viruses that’s endemic in swine (pigs). Early diagnosis and treatment is key approach to control the morbidity and mortality associated with swine flu which can be achieved by improving health seeking behaviour of community. Understanding of behaviour of community is essential for planning strategies for prevention and control. Aim of this study is to establish a relation between healthcare interval and outcome of swine flu.Methods: A complete data of all the patients visiting swine flu OPDs, swine flu wards and ICU were maintained for year 2015. Each patient visiting either the swine flu OPD or the swine flu ward, who was suspected clinically to be H1N1 positive were tested for real time PCR. Data was collected in a standardized pre-structured questionnaire.Results: Out of 1247 samples tested for rt-PCR, number of patients found to be swine positive was 491 (39.37%). Total 267 patients were admitted in swine flu ward and ICU, out of them 62 was expired. Clinical care intervals of more than 5 days from onset of symptoms to swab collection, diagnosis and admission were more in female and rural population. Mean duration between onset of symptom to hospitalization, swab collection and diagnosis was significantly higher in deceased patients than survived.Conclusions: Early presentation to healthcare facility is associated with better prognosis and outcome. After patient report to the health care setup, early sample collection and diagnosis help to reduce mortality.

scholarly journals Resurrected ancestral influenza A viruses recapitulate the avian-to-mammalian adaptation of European avian-like swine influenza virus

2021 ◽  
Author(s):  
Wen Su ◽  
Rhodri Harfoot ◽  
Yvonne Su ◽  
Jennifer DeBeauchamp ◽  
Udayan Joseph ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Avian Influenza ◽  
Influenza A ◽  
Swine Influenza Virus ◽  
Swine Influenza ◽  
Polymerase Activity ◽  
Influenza Viruses ◽  
Mammalian Host ◽  
Influenza A Viruses ◽  
Sequence Reconstruction

Abstract The emergence of a pandemic influenza virus may be better anticipated if we better understand the evolutionary steps taken by avian influenza viruses as they adapt to mammals. We used ancestral sequence reconstruction to resurrect viruses representing initial adaptive stages of the European avian-like H1N1 virus as it transitioned from avian to swine hosts. We demonstrate that efficient transmissibility in pigs was gained through stepwise adaptation after 1983. These time-dependent adaptations resulted in changes in hemagglutinin receptor binding specificity and increased viral polymerase activity. An NP-R351K mutation under strong positive selection increased the transmissibility of a reconstructed virus. The stepwise-adaptation of a wholly avian influenza virus to a mammalian host suggests a window where targeted intervention may have highest impact. Successful intervention will, however, require strategic coordination of surveillance and risk assessment activities to identify these adapting viruses and guide pandemic preparedness resources.

scholarly journals Cellular Innate Immunity against PRRSV and Swine Influenza Viruses

2019 ◽  
Vol 6 (1) ◽  
pp. 26 ◽  
Author(s):  
Elisa Crisci ◽  
Lorenzo Fraile ◽  
Maria Montoya
Keyword(s):  
Innate Immunity ◽  
T Cells ◽  
Natural Killer ◽  
Swine Influenza Virus ◽  
Swine Influenza ◽  
Γδ T Cells ◽  
Influenza Viruses ◽  
Production Costs ◽  
Respiratory Syndrome Virus

Porcine respiratory disease complex (PRDC) is a polymicrobial syndrome that results from a combination of infectious agents, such as environmental stressors, population size, management strategies, age, and genetics. PRDC results in reduced performance as well as increased mortality rates and production costs in the pig industry worldwide. This review focuses on the interactions of two enveloped RNA viruses—porcine reproductive and respiratory syndrome virus (PRRSV) and swine influenza virus (SwIV)—as major etiological agents that contribute to PRDC within the porcine cellular innate immunity during infection. The innate immune system of the porcine lung includes alveolar and parenchymal/interstitial macrophages, neutrophils (PMN), conventional dendritic cells (DC) and plasmacytoid DC, natural killer cells, and γδ T cells, thus the in vitro and in vivo interactions between those cells and PRRSV and SwIV are reviewed. Likewise, the few studies regarding PRRSV-SwIV co-infection are illustrated together with the different modulation mechanisms that are induced by the two viruses. Alterations in responses by natural killer (NK), PMN, or γδ T cells have not received much attention within the scientific community as their counterpart antigen-presenting cells and there are numerous gaps in the knowledge regarding the role of those cells in both infections. This review will help in paving the way for future directions in PRRSV and SwIV research and enhancing the understanding of the innate mechanisms that are involved during infection with these viruses.

Phylogeny of Spanish swine influenza viruses isolated from respiratory disease outbreaks and evolution of swine influenza virus within an endemically infected farm

2014 ◽  
Vol 170 (3-4) ◽  
pp. 266-277 ◽  
Author(s):  
Gerard E. Martín-Valls ◽  
Meritxell Simon-Grifé ◽  
Sander van Boheemen ◽  
Miranda de Graaf ◽  
Theo M. Bestebroer ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Respiratory Disease ◽  
Swine Influenza Virus ◽  
Swine Influenza ◽  
Disease Outbreaks ◽  
Influenza Viruses ◽  
Infected Farm
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