scholarly journals Heterologous Packaging Signals on Segment 4, but Not Segment 6 or Segment 8, Limit Influenza A Virus Reassortment

2017 ◽  
Vol 91 (11) ◽  
Author(s):  
Maria C. White ◽  
John Steel ◽  
Anice C. Lowen
Keyword(s):  
Public Health ◽  
Influenza A Virus ◽  
Influenza A ◽  
Influenza A Viruses ◽  
Packaging Signal ◽  
Significant Preference ◽  
Virus Reassortment ◽  
Segment 8 ◽  
The Impact ◽  
Packaging Signals

ABSTRACT Influenza A virus (IAV) RNA packaging signals serve to direct the incorporation of IAV gene segments into virus particles, and this process is thought to be mediated by segment-segment interactions. These packaging signals are segment and strain specific, and as such, they have the potential to impact reassortment outcomes between different IAV strains. Our study aimed to quantify the impact of packaging signal mismatch on IAV reassortment using the human seasonal influenza A/Panama/2007/99 (H3N2) and pandemic influenza A/Netherlands/602/2009 (H1N1) viruses. Focusing on the three most divergent segments, we constructed pairs of viruses that encoded identical proteins but differed in the packaging signal regions on a single segment. We then evaluated the frequency with which segments carrying homologous versus heterologous packaging signals were incorporated into reassortant progeny viruses. We found that, when segment 4 (HA) of coinfecting parental viruses was modified, there was a significant preference for the segment containing matched packaging signals relative to the background of the virus. This preference was apparent even when the homologous HA constituted a minority of the HA segment population available in the cell for packaging. Conversely, when segment 6 (NA) or segment 8 (NS) carried modified packaging signals, there was no significant preference for homologous packaging signals. These data suggest that movement of NA and NS segments between the human H3N2 and H1N1 lineages is unlikely to be restricted by packaging signal mismatch, while movement of the HA segment would be more constrained. Our results indicate that the importance of packaging signals in IAV reassortment is segment dependent. IMPORTANCE Influenza A viruses (IAVs) can exchange genes through reassortment. This process contributes to both the highly diverse population of IAVs found in nature and the formation of novel epidemic and pandemic IAV strains. Our study sought to determine the extent to which IAV packaging signal divergence impacts reassortment between seasonal IAVs. Our knowledge in this area is lacking, and insight into the factors that influence IAV reassortment will inform and strengthen ongoing public health efforts to anticipate the emergence of new viruses. We found that the packaging signals on the HA segment, but not the NA or NS segments, restricted IAV reassortment. Thus, the packaging signals of the HA segment could be an important factor in determining the likelihood that two IAV strains of public health interest will undergo reassortment.

scholarly journals Comparison of Adjuvanted-Whole Inactivated Virus and Live-Attenuated Virus Vaccines against Challenge with Contemporary, Antigenically Distinct H3N2 Influenza A Viruses

2018 ◽  
Vol 92 (22) ◽  
Author(s):  
Eugenio J. Abente ◽  
Daniela S. Rajao ◽  
Jefferson Santos ◽  
Bryan S. Kaplan ◽  
Tracy L. Nicholson ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Vaccine Efficacy ◽  
Influenza A ◽  
Rapid Evolution ◽  
The United States ◽  
Upper Respiratory Tract ◽  
Influenza A Viruses ◽  
Partial Protection ◽  
Attenuated Virus ◽  
The Impact

ABSTRACTInfluenza A viruses in swine (IAV-S) circulating in the United States of America are phylogenetically and antigenically distinct. A human H3 hemagglutinin (HA) was introduced into the IAV-S gene pool in the late 1990s, sustained continued circulation, and evolved into five monophyletic genetic clades, H3 clades IV-A to -E, after 2009. Across these phylogenetic clades, distinct antigenic clusters were identified, with three clusters (cyan, red, and green antigenic cluster) among the most frequently detected antigenic phenotypes (Abente EJ, Santos J, Lewis NS, Gauger PC, Stratton J, et al. J Virol 90:8266–8280, 2016,https://doi.org/10.1128/JVI.01002-16). Although it was demonstrated that antigenic diversity of H3N2 IAV-S was associated with changes at a few amino acid positions in the head of the HA, the implications of this diversity for vaccine efficacy were not tested. Using antigenically representative H3N2 viruses, we compared whole inactivated virus (WIV) and live-attenuated influenza virus (LAIV) vaccines for protection against challenge with antigenically distinct H3N2 viruses in pigs. WIV provided partial protection against antigenically distinct viruses but did not prevent virus replication in the upper respiratory tract. In contrast, LAIV provided complete protection from disease and virus was not detected after challenge with antigenically distinct viruses.IMPORTANCEDue to the rapid evolution of the influenza A virus, vaccines require continuous strain updates. Additionally, the platform used to deliver the vaccine can have an impact on the breadth of protection. Currently, there are various vaccine platforms available to prevent influenza A virus infection in swine, and we experimentally tested two: adjuvanted-whole inactivated virus and live-attenuated virus. When challenged with an antigenically distinct virus, adjuvanted-whole inactivated virus provided partial protection, while live-attenuated virus provided effective protection. Additional strategies are required to broaden the protective properties of inactivated virus vaccines, given the dynamic antigenic landscape of cocirculating strains in North America, whereas live-attenuated vaccines may require less frequent strain updates, based on demonstrated cross-protection. Enhancing vaccine efficacy to control influenza infections in swine will help reduce the impact they have on swine production and reduce the risk of swine-to-human transmission.

scholarly journals VirPreNet: A weighted ensemble convolutional neural network for the virulence prediction of influenza A virus using all 8 segments

2020 ◽  
Author(s):  
Rui Yin ◽  
Zihan Luo ◽  
Pei Zhuang ◽  
Zhuoyi Lin ◽  
Chee Keong Kwoh
Keyword(s):  
Public Health ◽  
Neural Network ◽  
Convolutional Neural Network ◽  
Influenza A Virus ◽  
Influenza A ◽  
Lethal Dose ◽  
Influenza Viruses ◽  
Numerical Representation ◽  
Influenza A Viruses ◽  
Linear Layer

AbstractMotivationInfluenza viruses are persistently threatening public health, causing annual epidemics and sporadic pandemics. The evolution of influenza viruses remains to be the main obstacle in the effectiveness of antiviral treatments due to rapid mutations. Previous work has been investigated to reveal the determinants of virulence of the influenza A virus. To further facilitate flu surveillance, explicit detection of influenza virulence is crucial to protect public health from potential future pandemics.ResultsIn this paper, we propose a weighted ensemble convolutional neural network for the virulence prediction of influenza A viruses named VirPreNet that uses all 8 segments. Firstly, mouse lethal dose 50 is exerted to label the virulence of infections into two classes, namely avirulent and virulent. A numerical representation of amino acids named ProtVec is applied to the 8-segments in a distributed manner to encode the biological sequences. After splittings and embeddings of influenza strains, the ensemble convolutional neural network is constructed as the base model on the influenza dataset of each segment, which serves as the VirPreNet’s main part. Followed by a linear layer, the initial predictive outcomes are integrated and assigned with different weights for the final prediction. The experimental results on the collected influenza dataset indicate that VirPreNet achieves state-of-the-art performance combining ProtVec with our proposed architecture. It outperforms baseline methods on the independent testing data. Moreover, our proposed model reveals the importance of PB2 and HA segments on the virulence prediction. We believe that our model may provide new insights into the investigation of influenza [email protected] and ImplementationCodes and data to generate the VirPreNet are publicly available at https://github.com/Rayin-saber/VirPreNet

scholarly journals An Intranasal Virus-Like Particle Vaccine Broadly Protects Mice from Multiple Subtypes of Influenza A Virus

mBio ◽  
2015 ◽  
Vol 6 (4) ◽  
Author(s):  
Louis M. Schwartzman ◽  
Andrea L. Cathcart ◽  
Lindsey M. Pujanauski ◽  
Li Qi ◽  
John C. Kash ◽  
...  
Keyword(s):  
Public Health ◽  
Influenza A Virus ◽  
Influenza A ◽  
Influenza Viruses ◽  
Significant Protection ◽  
Virus Infections ◽  
Influenza A Viruses ◽  
Virus Like Particle ◽  
Practical Strategy ◽  
Universal Influenza Vaccine

ABSTRACTInfluenza virus infections are a global public health problem, with a significant impact of morbidity and mortality from both annual epidemics and pandemics. The current strategy for preventing annual influenza is to develop a new vaccine each year against specific circulating virus strains. Because these vaccines are unlikely to protect against an antigenically divergent strain or a new pandemic virus with a novel hemagglutinin (HA) subtype, there is a critical need for vaccines that protect against all influenza A viruses, a so-called “universal” vaccine. Here we show that mice were broadly protected against challenge with a wide variety of lethal influenza A virus infections (94% aggregate survival following vaccination) with a virus-like particle (VLP) vaccine cocktail. The vaccine consisted of a mixture of VLPs individually displaying H1, H3, H5, or H7 HAs, and vaccinated mice showed significant protection following challenge with influenza viruses expressing 1918 H1, 1957 H2, and avian H5, H6, H7, H10, and H11 hemagglutinin subtypes. These experiments suggest a promising and practical strategy for developing a broadly protective “universal” influenza vaccine.IMPORTANCEThe rapid and unpredictable nature of influenza A virus evolution requires new vaccines to be produced annually to match circulating strains. Human infections with influenza viruses derived from animals can cause outbreaks that may be associated with high mortality, and such strains may also adapt to humans to cause a future pandemic. Thus, there is a large public health need to create broadly protective, or “universal,” influenza vaccines that could prevent disease from a wide variety of human and animal influenza A viruses. In this study, a noninfectious virus-like particle (VLP) vaccine was shown to offer significant protection against a variety of influenza A viruses in mice, suggesting a practical strategy to develop a universal influenza vaccine.

scholarly journals A Non-phylogeny-dependent Reassortment Detection Method for Influenza A Viruses

2021 ◽  
Vol 1 ◽  
Author(s):  
Xingfei Gong ◽  
Mingda Hu ◽  
Boqian Wang ◽  
Haoyi Yang ◽  
Yuan Jin ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Detection Method ◽  
Rna Virus ◽  
Self Organizing Map ◽  
Influenza A Viruses ◽  
Multiple Sequence ◽  
Distance Methods ◽  
Virus Reassortment ◽  
Pandemic Strains

Influenza A virus is a segmented RNA virus whose genome consists of 8 single-stranded negative-sense RNA segments. This unique genetic structure allows viruses to exchange their segments through reassortment when they infect the same host cell. Studying the determination and nature of influenza A virus reassortment is critical to understanding the generation of pandemic strains and the spread of viruses across species. Reassortment detection is the first step in influenza A virus reassortment research. Several methods for automatic detection of reassortment have been proposed, which can be roughly divided into two categories: phylogenetic methods and distance methods. In this article, we proposed a reassortment detection method that does not require multiple sequence alignment and phylogenetic analysis. We extracted the codon features from the segment sequence and expressed the sequence as a feature vector, and then used the clustering method of self-organizing map to cluster the sequence for each segment. Based on the clustering results and the epidemiological information of the virus, the reassortment detection was implemented. We used this method to perform reassortment detection on the collected 7,075 strains from Asia and identified 516 reassortment events. We also conducted a statistical analysis of the identified reassortment events and found conclusions consistent with previous studies. Our method will provide new insights for automating reassortment detection tasks and understanding the reassortment patterns of influenza A viruses.

scholarly journals Packaging signal of influenza A virus

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Xiuli Li ◽  
Min Gu ◽  
Qinmei Zheng ◽  
Ruyi Gao ◽  
Xiufan Liu
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Packaging Signal ◽  
Genome Packaging ◽  
Genetic Reassortment ◽  
A Genome ◽  
Virus Genotypes ◽  
Virus Packaging ◽  
Negative Sense ◽  
Packaging Signals

AbstractInfluenza A virus (IAV) contains a genome with eight single-stranded, negative-sense RNA segments that encode 17 proteins. During its assembly, all eight separate viral RNA (vRNA) segments are incorporated into virions in a selective manner. Evidence suggested that the highly selective genome packaging mechanism relies on RNA-RNA or protein-RNA interactions. The specific structures of each vRNA that contribute to mediating the packaging of the vRNA into virions have been described and identified as packaging signals. Abundant research indicated that sequences required for genome incorporation are not series and are varied among virus genotypes. The packaging signals play important roles in determining the virus replication, genome incorporation and genetic reassortment of influenza A virus. In this review, we discuss recent studies on influenza A virus packaging signals to provide an overview of their characteristics and functions.

scholarly journals Influenza A Virus Reassortment Is Limited by Anatomical Compartmentalization following Coinfection via Distinct Routes

2017 ◽  
Vol 92 (5) ◽  
Author(s):  
Mathilde Richard ◽  
Sander Herfst ◽  
Hui Tao ◽  
Nathan T. Jacobs ◽  
Anice C. Lowen
Keyword(s):  
Respiratory Tract ◽  
Influenza A Virus ◽  
Lower Respiratory Tract ◽  
Influenza A ◽  
Upper Respiratory Tract ◽  
Extrinsic Factors ◽  
Genetic Incompatibility ◽  
Viral Spread ◽  
Virus Reassortment ◽  
The Impact

ABSTRACTExchange of gene segments through reassortment is a major feature of influenza A virus evolution and frequently contributes to the emergence of novel epidemic, pandemic, and zoonotic strains. It has long been evident that viral diversification through reassortment is constrained by genetic incompatibility between divergent parental viruses. In contrast, the role of virus-extrinsic factors in determining the likelihood of reassortment has remained unclear. To evaluate the impact of such factors in the absence of confounding effects of segment mismatch, we previously reported an approach in which reassortment between wild-type (wt) and genetically tagged variant (var) viruses of the same strain is measured. Here, using wt/var systems in the A/Netherlands/602/2009 (pH1N1) and A/Panama/2007/99 (H3N2) strain backgrounds, we tested whether inoculation of parental viruses into distinct sites within the respiratory tract limits their reassortment. Using a ferret (Mustella putorius furo) model, either matched parental viruses were coinoculated intranasally or one virus was instilled intranasally whereas the second was instilled intratracheally. Dual intranasal inoculation resulted in robust reassortment for wt/var viruses of both strain backgrounds. In contrast, when infections were initiated simultaneously at distinct sites, strong compartmentalization of viral replication was observed and minimal reassortment was detected. The observed lack of viral spread between upper and lower respiratory tract tissues may be attributable to localized exclusion of superinfection within the host, mediated by innate immune responses. Our findings indicate that dual infections in nature are more likely to result in reassortment if viruses are seeded into similar anatomical locations and have matched tissue tropisms.IMPORTANCEGenetic exchange between influenza A viruses (IAVs) through reassortment can facilitate the emergence of antigenically drifted seasonal strains and plays a prominent role in the development of pandemics. Typical human influenza infections are concentrated in the upper respiratory tract; however, lower respiratory tract (LRT) infection is an important feature of severe cases, which are more common in the very young, the elderly, and individuals with underlying conditions. In addition to host factors, viral characteristics and mode of transmission can also increase the likelihood of LRT infection: certain zoonotic IAVs are thought to favor the LRT, and transmission via small droplets allows direct seeding into lower respiratory tract tissues. To gauge the likelihood of reassortment in coinfected hosts, we assessed the extent to which initiation of infection at distinct respiratory tract sites impacts reassortment frequency. Our results reveal that spatially distinct inoculations result in anatomical compartmentalization of infection, which in turn strongly limits reassortment.

scholarly journals VirPreNet: a weighted ensemble convolutional neural network for the virulence prediction of influenza A virus using all eight segments

2020 ◽  
Author(s):  
Rui Yin ◽  
Zihan Luo ◽  
Pei Zhuang ◽  
Zhuoyi Lin ◽  
Chee Keong Kwoh
Keyword(s):  
Public Health ◽  
Neural Network ◽  
Convolutional Neural Network ◽  
Influenza A Virus ◽  
Influenza A ◽  
Lethal Dose ◽  
Influenza Viruses ◽  
Supplementary Information ◽  
Numerical Representation ◽  
Influenza A Viruses

Abstract Motivation Influenza viruses are persistently threatening public health, causing annual epidemics and sporadic pandemics. The evolution of influenza viruses remains to be the main obstacle in the effectiveness of antiviral treatments due to rapid mutations. Previous work has been investigated to reveal the determinants of virulence of the influenza A virus. To further facilitate flu surveillance, explicit detection of influenza virulence is crucial to protect public health from potential future pandemics. Results In this article, we propose a weighted ensemble convolutional neural network (CNN) for the virulence prediction of influenza A viruses named VirPreNet that uses all eight segments. Firstly, mouse lethal dose 50 is exerted to label the virulence of infections into two classes, namely avirulent and virulent. A numerical representation of amino acids named ProtVec is applied to the eight-segments in a distributed manner to encode the biological sequences. After splittings and embeddings of influenza strains, the ensemble CNN is constructed as the base model on the influenza dataset of each segment, which serves as the VirPreNet’s main part. Followed by a linear layer, the initial predictive outcomes are integrated and assigned with different weights for the final prediction. The experimental results on the collected influenza dataset indicate that VirPreNet achieves state-of-the-art performance combining ProtVec with our proposed architecture. It outperforms baseline methods on the independent testing data. Moreover, our proposed model reveals the importance of PB2 and HA segments on the virulence prediction. We believe that our model may provide new insights into the investigation of influenza virulence. Availability and implementation Codes and data to generate the VirPreNet are publicly available at https://github.com/Rayin-saber/VirPreNet. Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals Role of the B Allele of Influenza A Virus Segment 8 in Setting Mammalian Host Range and Pathogenicity

2016 ◽  
Vol 90 (20) ◽  
pp. 9263-9284 ◽  
Author(s):  
Matthew L. Turnbull ◽  
Helen M. Wise ◽  
Marlynne Q. Nicol ◽  
Nikki Smith ◽  
Rebecca L. Dunfee ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
H3n2 Virus ◽  
Mammalian Host ◽  
Influenza A Viruses ◽  
Content Type ◽  
Avian Virus ◽  
Segment 8 ◽  
Reassortant Viruses

ABSTRACTTwo alleles of segment 8 (NS) circulate in nonchiropteran influenza A viruses. The A allele is found in avian and mammalian viruses, but the B allele is viewed as being almost exclusively found in avian viruses. This might reflect the fact that one or both of its encoded proteins (NS1 and NEP) are maladapted for replication in mammalian hosts. To test this, a number of clade A and B avian virus-derived NS segments were introduced into human H1N1 and H3N2 viruses. In no case was the peak virus titer substantially reduced following infection of various mammalian cell types. Exemplar reassortant viruses also replicated to similar titers in mice, although mice infected with viruses with the avian virus-derived segment 8s had reduced weight loss compared to that achieved in mice infected with the A/Puerto Rico/8/1934 (H1N1) parent.In vitro, the viruses coped similarly with type I interferons. Temporal proteomics analysis of cellular responses to infection showed that the avian virus-derived NS segments provoked lower levels of expression of interferon-stimulated genes in cells than wild type-derived NS segments. Thus, neither the A nor the B allele of avian virus-derived NS segments necessarily attenuates virus replication in a mammalian host, although the alleles can attenuate disease. Phylogenetic analyses identified 32 independent incursions of an avian virus-derived A allele into mammals, whereas 6 introductions of a B allele were identified. However, A-allele isolates from birds outnumbered B-allele isolates, and the relative rates ofAves-to-Mammaliatransmission were not significantly different. We conclude that while the introduction of an avian virus segment 8 into mammals is a relatively rare event, the dogma of the B allele being especially restricted is misleading, with implications in the assessment of the pandemic potential of avian influenza viruses.IMPORTANCEInfluenza A virus (IAV) can adapt to poultry and mammalian species, inflicting a great socioeconomic burden on farming and health care sectors. Host adaptation likely involves multiple viral factors. Here, we investigated the role of IAV segment 8. Segment 8 has evolved into two distinct clades: the A and B alleles. The B-allele genes have previously been suggested to be restricted to avian virus species. We introduced a selection of avian virus A- and B-allele segment 8s into human H1N1 and H3N2 virus backgrounds and found that these reassortant viruses were fully competent in mammalian host systems. We also analyzed the currently available public data on the segment 8 gene distribution and found surprisingly little evidence for specific avian host restriction of the B-clade segment. We conclude that B-allele segment 8 genes are, in fact, capable of supporting infection in mammals and that they should be considered during the assessment of the pandemic risk of zoonotic influenza A viruses.

scholarly journals The Effects of Social Distancing Policies on non-SARS-CoV-2 Respiratory Pathogens

2021 ◽  
Author(s):  
Jeff Nawrocki ◽  
Katherine Olin ◽  
Martin C Holdrege ◽  
Joel Hartsell ◽  
Lindsay Meyers ◽  
...  
Keyword(s):  
Public Health ◽  
Influenza A ◽  
Detection Rate ◽  
Respiratory Illness ◽  
Respiratory Pathogens ◽  
Public Health Response ◽  
Mixed Effect ◽  
Detection Rates ◽  
Social Distancing ◽  
The Impact

Abstract Background The initial focus of the US public health response to COVID-19 was the implementation of numerous social distancing policies. While COVID-19 was the impetus for imposing these policies, it is not the only respiratory disease affected by their implementation. This study aimed to assess the impact of social distancing policies on non-SARS-CoV-2 respiratory pathogens typically circulating across multiple US states. Methods Linear mixed-effect models were implemented to explore the effects of five social distancing policies on non-SARS-CoV-2 respiratory pathogens across nine states from January 1 through May 1, 2020. The observed 2020 pathogen detection rates were compared week-by-week to historical rates to determine when the detection rates were different. Results Model results indicate that several social distancing policies were associated with a reduction in total detection rate, by nearly 15%. Policies were associated with decreases in pathogen circulation of human rhinovirus/enterovirus and human metapneumovirus, as well as influenza A, which typically decrease after winter. Parainfluenza viruses failed to circulate at historical levels during the spring. Total detection rate in April 2020 was 35% less than historical average. Many of the pathogens driving this difference fell below historical detection rate ranges within two weeks of initial policy implementation. Conclusion This analysis investigated the effect of multiple social distancing policies implemented to reduce transmission of SARS-CoV-2 on non-SARS-CoV-2 respiratory pathogens. These findings suggest that social distancing policies may be used as an impactful public health tool to reduce communicable respiratory illness.

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