scholarly journals Upstream translation initiation expands the coding capacity of segmented negative-strand RNA viruses

2019 ◽  
Author(s):  
Elizabeth Sloan ◽  
Marta Alenquer ◽  
Liliane Chung ◽  
Sara Clohisey ◽  
Adam M. Dinan ◽  
...  
Keyword(s):  
Translation Initiation ◽  
Influenza A ◽  
Viral Infections ◽  
Rna Viruses ◽  
Influenza Viruses ◽  
Open Reading Frames ◽  
Viral Gene ◽  
Influenza A Viruses ◽  
Negative Strand ◽  
Coding Potential

AbstractSegmented negative-strand RNA viruses (sNSVs) include the influenza viruses, the bunyaviruses, and other major pathogens of humans, other animals and plants. The genomes of these viruses are extremely short. In response to this severe genetic constraint, sNSVs use a variety of strategies to maximise their coding potential. Because the eukaryotic hosts parasitized by sNSVs can regulate gene expression through low levels of translation initiation upstream of their canonical open reading frames (ORFs), we asked whether sNSVs could use upstream translation initiation to expand their own genetic repertoires. Consistent with this hypothesis, we showed that influenza A viruses (IAVs) and bunyaviruses were capable of upstream translation initiation. Using a combination of reporter assays and viral infections, we found that upstream translation in IAVs can initiate in two unusual ways: through non-AUG initiation in virally encoded ‘untranslated’ regions, and through the appropriation of an AUG-containing leader sequence from host mRNAs through viral cap-snatching, a process we termed ‘start-snatching.’ Finally, while upstream translation of cellular genes is mainly regulatory, for sNSVs it also has the potential to create novel viral gene products. If in frame with a viral ORF, this creates N-extensions of canonical viral proteins. If not, it allows the expression of cryptic overlapping ORFs, which we found were highly conserved in IAV and widely distributed in peribunyaviruses. Thus, by exploiting their host’s capacity for upstream translation initiation, sNSVs can expand still further the coding potential of their extremely compact RNA genomes.

scholarly journals Non-Uniform and Non-Random Binding of Nucleoprotein to Influenza A and B Viral RNA

Viruses ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 522 ◽  
Author(s):  
Valerie Le Sage ◽  
Adalena Nanni ◽  
Amar Bhagwat ◽  
Dan Snyder ◽  
Vaughn Cooper ◽  
...  
Keyword(s):  
Influenza A ◽  
Gene Segment ◽  
Influenza Viruses ◽  
Viral Rna ◽  
Influenza B Virus ◽  
Viral Gene ◽  
Influenza B ◽  
Influenza A Viruses ◽  
Binding Profile ◽  
Random Manner

The genomes of influenza A and B viruses have eight, single-stranded RNA segments that exist in the form of a viral ribonucleoprotein complex in association with nucleoprotein (NP) and an RNA-dependent RNA polymerase complex. We previously used high-throughput RNA sequencing coupled with crosslinking immunoprecipitation (HITS-CLIP) to examine where NP binds to the viral RNA (vRNA) and demonstrated for two H1N1 strains that NP binds vRNA in a non-uniform, non-random manner. In this study, we expand on those initial observations and describe the NP-vRNA binding profile for a seasonal H3N2 and influenza B virus. We show that, similar to H1N1 strains, NP binds vRNA in a non-uniform and non-random manner. Each viral gene segment has a unique NP binding profile with areas that are enriched for NP association as well as free of NP-binding. Interestingly, NP-vRNA binding profiles have some conservation between influenza A viruses, H1N1 and H3N2, but no correlation was observed between influenza A and B viruses. Our study demonstrates the conserved nature of non-uniform NP binding within influenza viruses. Mapping of the NP-bound vRNA segments provides information on the flexible NP regions that may be involved in facilitating assembly.

scholarly journals An evaluation of the InDevR FluChip-8G insight microarray assay in characterizing influenza a viruses

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Emily S. Bailey ◽  
Xinye Wang ◽  
Mai-juan Ma ◽  
Guo-lin Wang ◽  
Gregory C. Gray
Keyword(s):  
Influenza A ◽  
Influenza Viruses ◽  
Time Range ◽  
Influenza B ◽  
Influenza A Viruses ◽  
Laboratory Methods ◽  
Duke University ◽  
Multiple Viral Strains ◽  
Rapid Characterization

AbstractInfluenza viruses are an important cause of disease in both humans and animals, and their detection and characterization can take weeks. In this study, we sought to compare classical virology techniques with a new rapid microarray method for the detection and characterization of a very diverse, panel of animal, environmental, and human clinical or field specimens that were molecularly positive for influenza A alone (n = 111), influenza B alone (n = 3), both viruses (n = 13), or influenza negative (n = 2) viruses. All influenza virus positive samples in this study were first subtyped by traditional laboratory methods, and later evaluated using the FluChip-8G Insight Assay (InDevR Inc. Boulder, CO) in laboratories at Duke University (USA) or at Duke Kunshan University (China). The FluChip-8G Insight multiplexed assay agreed with classical virologic techniques 59 (54.1%) of 109 influenza A-positive, 3 (100%) of the 3 influenza B-positive, 0 (0%) of 10 both influenza A- and B-positive samples, 75% of 24 environmental samples including those positive for H1, H3, H7, H9, N1, and N9 strains, and 80% of 22 avian influenza samples. It had difficulty with avian N6 types and swine H3 and N2 influenza specimens. The FluChip-8G Insight assay performed well with most human, environmental, and animal samples, but had some difficulty with samples containing multiple viral strains and with specific animal influenza strains. As classical virology methods are often iterative and can take weeks, the FluChip-8G Insight Assay rapid results (time range 8 to 12 h) offers considerable time savings. As the FluChip-8G analysis algorithm is expected to improve over time with addition of new subtypes and sample matrices, the FluChip-8G Insight Assay has considerable promise for rapid characterization of novel influenza viruses affecting humans or animals.

scholarly journals PRESENCE OF RESPIRATORY VIRUSES IN EQUINES IN BRAZIL

2014 ◽  
Vol 56 (3) ◽  
pp. 191-195
Author(s):  
Dalva Assunção Portari Mancini ◽  
Aparecida Santo Pietro Pereira ◽  
Rita Maria Zucatelli Mendonça ◽  
Adelia Hiroko Nagamori Kawamoto ◽  
Rosely Cabette Barbosa Alves ◽  
...  
Keyword(s):  
Influenza A ◽  
Respiratory Viruses ◽  
Influenza Viruses ◽  
Influenza A Viruses ◽  
Equine Influenza ◽  
Hemagglutination Inhibition Test ◽  
Parainfluenza Viruses ◽  
Significant Difference ◽  
Antibody Titers ◽  
The Difference

Equines are susceptible to respiratory viruses such as influenza and parainfluenza. Respiratory diseases have adversely impacted economies all over the world. This study was intended to determine the presence of influenza and parainfluenza viruses in unvaccinated horses from some regions of the state of São Paulo, Brazil. Blood serum collected from 72 equines of different towns in this state was tested by hemagglutination inhibition test to detect antibodies for both viruses using the corresponding antigens. About 98.6% (71) and 97.2% (70) of the equines responded with antibody protective titers (≥ 80 HIU/25µL) H7N7 and H3N8 subtypes of influenza A viruses, respectively. All horses (72) also responded with protective titers (≥ 80) HIU/25µL against the parainfluenza virus. The difference between mean antibody titers to H7N7 and H3N8 subtypes of influenza A viruses was not statistically significant (p > 0.05). The mean titers for influenza and parainfluenza viruses, on the other hand, showed a statistically significant difference (p < 0.001). These results indicate a better antibody response from equines to parainfluenza 3 virus than to the equine influenza viruses. No statistically significant differences in the responses against H7N7 and H3N8 subtypes of influenza A and parainfluenza 3 viruses were observed according to the gender (female, male) or the age (≤ 2 to 20 years-old) groups. This study provides evidence of the concomitant presence of two subtypes of the equine influenza A (H7N7 and H3N8) viruses and the parainfluenza 3 virus in equines in Brazil. Thus, it is advisable to vaccinate equines against these respiratory viruses.

scholarly journals Influenza: An Emerging and Re-emerging Public Health Threat in Nepal

2018 ◽  
Vol 3 (2) ◽  
pp. 1-2
Author(s):  
Bishnu Prasad Upadhyay
Keyword(s):  
Influenza Virus ◽  
Influenza A ◽  
Winter Season ◽  
Emerging Infectious Diseases ◽  
Influenza Viruses ◽  
Influenza B ◽  
Influenza A Viruses ◽  
Influenza A H1n1 ◽  
New Variant ◽  
Seasonal Epidemics

Influenza virus type A and B are responsible for seasonal epidemics as well as pandemics in human. Influenza A viruses are further divided into two major groups namely, low pathogenic seasonal influenza (A/H1N1, A/H1N1 pdm09, A/H3N2) and highly pathogenic influenza virus (H5N1, H5N6, H7N9) on the basis of two surface antigens: hemagglutinin (HA) and neuraminidase (NA). Mutations, including substitutions, deletions, and insertions, are one of the most important mechanisms for producing new variant of influenza viruses. During the last 30 years; more than 50 viral threat has been evolved in South-East Asian countriesof them influenza is one of the major emerging and re-emerging infectious diseases of global concern. Similar to tropical and sub-tropical countries of Southeast Asia; circulation of A/H1N1 pdm09, A/H3N2 and influenza B has been circulating throughout the year with the peak during July-November in Nepal. However; the rate of infection transmission reach peak during the post-rain and winter season of Nepal.

Swine influenza vaccines: current status and future perspectives

2010 ◽  
Vol 11 (1) ◽  
pp. 81-96 ◽  
Author(s):  
Wenjun Ma ◽  
Jürgen A. Richt
Keyword(s):  
Influenza A ◽  
Swine Influenza ◽  
Influenza Viruses ◽  
Current Status ◽  
Economic Losses ◽  
Influenza A Viruses ◽  
Swine Industry ◽  
Effective Strategies ◽  
Swine Disease ◽  
And Control

AbstractSwine influenza is an important contagious disease in pigs caused by influenza A viruses. Although only three subtypes of influenza A viruses, H1N1, H1N2 and H3N2, predominantly infect pigs worldwide, it is still a big challenge for vaccine manufacturers to produce efficacious vaccines for the prevention and control of swine influenza. Swine influenza viruses not only cause significant economic losses for the swine industry, but are also important zoonotic pathogens. Vaccination is still one of the most important and effective strategies to prevent and control influenza for both the animal and human population. In this review, we will discuss the current status of swine influenza worldwide as well as current and future options to control this economically important swine disease.

scholarly journals N-Glycolylneuraminic Acid in Animal Models for Human Influenza A Virus

Viruses ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 815
Author(s):  
Cindy M. Spruit ◽  
Nikoloz Nemanichvili ◽  
Masatoshi Okamatsu ◽  
Hiromu Takematsu ◽  
Geert-Jan Boons ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Animal Models ◽  
Influenza A ◽  
Influenza Virus Infection ◽  
Influenza Viruses ◽  
Upper Respiratory Tract ◽  
Human Influenza ◽  
Influenza A Viruses ◽  
Sialic Acid Content ◽  
Acetylneuraminic Acid

The first step in influenza virus infection is the binding of hemagglutinin to sialic acid-containing glycans present on the cell surface. Over 50 different sialic acid modifications are known, of which N-acetylneuraminic acid (Neu5Ac) and N-glycolylneuraminic acid (Neu5Gc) are the two main species. Animal models with α2,6 linked Neu5Ac in the upper respiratory tract, similar to humans, are preferred to enable and mimic infection with unadapted human influenza A viruses. Animal models that are currently most often used to study human influenza are mice and ferrets. Additionally, guinea pigs, cotton rats, Syrian hamsters, tree shrews, domestic swine, and non-human primates (macaques and marmosets) are discussed. The presence of NeuGc and the distribution of sialic acid linkages in the most commonly used models is summarized and experimentally determined. We also evaluated the role of Neu5Gc in infection using Neu5Gc binding viruses and cytidine monophosphate-N-acetylneuraminic acid hydroxylase (CMAH)-/- knockout mice, which lack Neu5Gc and concluded that Neu5Gc is unlikely to be a decoy receptor. This article provides a base for choosing an appropriate animal model. Although mice are one of the most favored models, they are hardly naturally susceptible to infection with human influenza viruses, possibly because they express mainly α2,3 linked sialic acids with both Neu5Ac and Neu5Gc modifications. We suggest using ferrets, which resemble humans closely in the sialic acid content, both in the linkages and the lack of Neu5Gc, lung organization, susceptibility, and disease pathogenesis.

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.

Evolution of the NS genes of the influenza a viruses. I. The genetic relatedness of the NS genes of animal influenza viruses

Virus Genes ◽  
1990 ◽  
Vol 4 (1) ◽  
pp. 5-13 ◽  
Author(s):  
Katsuhisa Nakajima ◽  
Eri Nobusawa ◽  
Takashi Ogawa ◽  
Setsuko Nakajima
Keyword(s):  
Influenza A ◽  
Genetic Relatedness ◽  
Influenza Viruses ◽  
Influenza A Viruses

scholarly journals Plasticity of the Influenza Virus H5 HA Protein

mBio ◽  
2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Huihui Kong ◽  
David F. Burke ◽  
Tiago Jose da Silva Lopes ◽  
Kosuke Takada ◽  
Masaki Imai ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Amino Acid ◽  
Mammalian Cells ◽  
Influenza A ◽  
Viral Antigen ◽  
Influenza Viruses ◽  
Influenza A Viruses ◽  
Highly Pathogenic ◽  
Antigenic Properties ◽  
Ha Protein

ABSTRACT Since the emergence of highly pathogenic avian influenza viruses of the H5 subtype, the major viral antigen, hemagglutinin (HA), has undergone constant evolution, resulting in numerous genetic and antigenic (sub)clades. To explore the consequences of amino acid changes at sites that may affect the antigenicity of H5 viruses, we simultaneously mutated 17 amino acid positions of an H5 HA by using a synthetic gene library that, theoretically, encodes all combinations of the 20 amino acids at the 17 positions. All 251 mutant viruses sequenced possessed ≥13 amino acid substitutions in HA, demonstrating that the targeted sites can accommodate a substantial number of mutations. Selection with ferret sera raised against H5 viruses of different clades resulted in the isolation of 39 genotypes. Further analysis of seven variants demonstrated that they were antigenically different from the parental virus and replicated efficiently in mammalian cells. Our data demonstrate the substantial plasticity of the influenza virus H5 HA protein, which may lead to novel antigenic variants. IMPORTANCE The HA protein of influenza A viruses is the major viral antigen. In this study, we simultaneously introduced mutations at 17 amino acid positions of an H5 HA expected to affect antigenicity. Viruses with ≥13 amino acid changes in HA were viable, and some had altered antigenic properties. H5 HA can therefore accommodate many mutations in regions that affect antigenicity. The substantial plasticity of H5 HA may facilitate the emergence of novel antigenic variants.

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