Special Issue "Non-A Influenza 2.0"

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Animal Viruses".

Deadline for manuscript submissions: 31 December 2021.

Special Issue Editor

Prof. Dr. Feng Li
E-Mail Website
Guest Editor
Dept. Biology & Microbiology. Dept. Veterinary & Biomedical Sciences, South Dakota State University, Brookings, SD 57007, USA
Interests: influenza D and comparative influenza biology; virus assembly and maturation; antiviral therapeutics and vaccine; veterinary virology
Special Issues and Collections in MDPI journals

Special Issue Information

Dear Colleagues,

Influenza viruses are a group of respiratory pathogens that have been classified into four types in the family Orthomyxoviridae: A, B, C, and D. Among them, influenza A and B viruses can cause moderate to severe illness in humans, with influenza A having the potential to trigger an influenza pandemic. Influenza C virus generally causes mild reparatory disease in humans, but its infection can be severe with complications including lower respiratory infection in children, especially those under two years. The recently discovered influenza D primarily affects agricultural animals, with bovines as a reservoir. Of greater public health importance, serological evidence of influenza D virus infection in humans has been recently demonstrated. Within global influenza research, influenza A has been primarily investigated due to its pandemic potential. In contrast, other types of influenza viruses, including influenza B with humans as a primary reservoir, have received considerably less attention. This Special Issue will feature the most recent research and findings on non-A influenza viruses, including epidemiology, evolution, cross-species transmission, molecular biology, antigenic lineage, virus–host interactions, antivirals and vaccine development.

Prof. Dr. Feng Li
Guest Editor

Manuscript Submission Information

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Keywords

  • orthomyxoviruses
  • influenza B
  • influenza C
  • influenza D
  • epidemiology
  • evolution
  • transmission
  • molecular biology
  • antigenic lineage
  • reverse genetics
  • virus–host interactions
  • antivirals

Published Papers (4 papers)

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Research

Article
Tissue Microarrays to Visualize Influenza D Attachment to Host Receptors in the Respiratory Tract of Farm Animals
Viruses 2021, 13(4), 586; https://doi.org/10.3390/v13040586 - 31 Mar 2021
Viewed by 835
Abstract
The trimeric hemagglutinin-esterase fusion protein (HEF) of influenza D virus (IDV) binds 9-O-acetylated sialic acid receptors, which are expressed in various host species. While cattle are the main reservoir for IDV, the viral genome has also been detected in domestic pigs. In addition, [...] Read more.
The trimeric hemagglutinin-esterase fusion protein (HEF) of influenza D virus (IDV) binds 9-O-acetylated sialic acid receptors, which are expressed in various host species. While cattle are the main reservoir for IDV, the viral genome has also been detected in domestic pigs. In addition, antibodies against IDV have been detected in other farm animals such as sheep, goats, and horses, and even in farmers working with IDV positive animals. Viruses belonging to various IDV clades circulate, but little is known about their differences in host and tissue tropism. Here we used recombinantly produced HEF proteins (HEF S57A) from the major clades D/Oklahoma (D/OK) and D/Oklahoma/660 (D/660) to study their host and tissue tropism and receptor interactions. To this end, we developed tissue microarrays (TMA) composed of respiratory tissues from various farm animals including cattle, domestic pigs, sheep, goats, and horses. Protein histochemical staining of farm animal respiratory tissue-microarrays with HEF proteins showed that cattle have receptors present over the entire respiratory tract while receptors are only present in the nasal and pharyngeal epithelium of pigs, sheep, goats, and horses. No differences in tropism for tissues and animals were observed between clades, while hemagglutination assays showed that D/OK has a 2-fold higher binding affinity than D/660 for receptors on red blood cells. The removal of O-acetylation from receptors via saponification treatment confirmed that receptor-binding of both clades was dependent on O-acetylated sialic acids. Full article
(This article belongs to the Special Issue Non-A Influenza 2.0)
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Article
Establishment of a Reverse Genetic System from a Bovine Derived Influenza D Virus Isolate
Viruses 2021, 13(3), 502; https://doi.org/10.3390/v13030502 - 18 Mar 2021
Viewed by 999
Abstract
The ruminant-associated influenza D virus (IDV) has a broad host tropism and was shown to have zoonotic potential. To identify and characterize molecular viral determinants influencing the host spectrum of IDV, a reverse genetic system is required. For this, we first performed 5′ [...] Read more.
The ruminant-associated influenza D virus (IDV) has a broad host tropism and was shown to have zoonotic potential. To identify and characterize molecular viral determinants influencing the host spectrum of IDV, a reverse genetic system is required. For this, we first performed 5′ and 3′ rapid amplification of cDNA ends (RACE) of all seven genomic segments, followed by assessment of the 5′ and 3′ NCR activity prior to constructing the viral genomic segments of a contemporary Swiss bovine IDV isolate (D/CN286) into the bidirectional pHW2000 vector. The bidirectional plasmids were transfected in HRT-18G cells followed by viral rescue on the same cell type. Analysis of the segment specific 5′ and 3′ non-coding regions (NCR) highlighted that the terminal 3′ end of all segments harbours an uracil instead of a cytosine nucleotide, similar to other influenza viruses. Subsequent analysis on the functionality of the 5′ and 3′ NCR in a minireplicon assay revealed that these sequences were functional and that the variable sequence length of the 5′ and 3′ NCR influences reporter gene expression. Thereafter, we evaluated the replication efficiency of the reverse genetic clone on conventional cell lines of human, swine and bovine origin, as well as by using an in vitro model recapitulating the natural replication site of IDV in bovine and swine. This revealed that the reverse genetic clone D/CN286 replicates efficiently in all cell culture models. Combined, these results demonstrate the successful establishment of a reverse genetic system from a contemporary bovine IDV isolate that can be used for future identification and characterization of viral determinants influencing the broad host tropism of IDV. Full article
(This article belongs to the Special Issue Non-A Influenza 2.0)
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Article
Growth Kinetics of Influenza C Virus Antigenic Mutants That Escaped from Anti-Hemagglutinin Esterase Monoclonal Antibodies and Viral Antigenic Changes Found in Field Isolates
Viruses 2021, 13(3), 401; https://doi.org/10.3390/v13030401 - 03 Mar 2021
Viewed by 427
Abstract
The antigenicity of the hemagglutinin esterase (HE) glycoprotein of influenza C virus is known to be stable; however, information about residues related to antigenic changes has not yet been fully acquired. Using selection with anti-HE monoclonal antibodies, we previously obtained some escape mutants [...] Read more.
The antigenicity of the hemagglutinin esterase (HE) glycoprotein of influenza C virus is known to be stable; however, information about residues related to antigenic changes has not yet been fully acquired. Using selection with anti-HE monoclonal antibodies, we previously obtained some escape mutants and identified four antigenic sites, namely, A-1, A-2, A-3, and Y-1. To confirm whether the residues identified as the neutralizing epitope possibly relate to the antigenic drift, we analyzed the growth kinetics of these mutants. The results showed that some viruses with mutations in antigenic site A-1 were able to replicate to titers comparable to that of the wild-type, while others showed reduced titers. The mutants possessing substitutions in the A-2 or A-3 site replicated as efficiently as the wild-type virus. Although the mutant containing a deletion at positions 192 to 195 in the Y-1 site showed lower titers than the wild-type virus, it was confirmed that this region in the 190-loop on the top side of the HE protein is not essential for viral propagation. Then, we revealed that antigenic changes due to substitutions in the A-1, A-3, and/or Y-1 site had occurred in nature in Japan for the past 30 years. These results suggest that some residues (i.e., 125, 176, 192) in the A-1 site, residue 198 in the A-3 site, and residue 190 in the Y-1 site are likely to mediate antigenic drift while maintaining replicative ability. Full article
(This article belongs to the Special Issue Non-A Influenza 2.0)
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Article
Features of Nuclear Export Signals of NS2 Protein of Influenza D Virus
Viruses 2020, 12(10), 1100; https://doi.org/10.3390/v12101100 - 29 Sep 2020
Cited by 1 | Viewed by 719
Abstract
Emerging influenza D viruses (IDVs), the newest member in the genus Orthomyxovirus family, which can infect and transmit in multiple mammalian species as its relatives the influenza A viruses (IAVs). Additional studies of biological characteristics of IDVs are needed; here, we studied the [...] Read more.
Emerging influenza D viruses (IDVs), the newest member in the genus Orthomyxovirus family, which can infect and transmit in multiple mammalian species as its relatives the influenza A viruses (IAVs). Additional studies of biological characteristics of IDVs are needed; here, we studied the characteristics of IDV nonstructural protein 2 (NS2), which shares the lowest homology to known influenza proteins. First, we generated reassortant viruses via reverse genetics to analyze the segment compatibility and gene interchangeability between IAVs and IDVs. Next, we investigated the locations and exact sequences of nuclear export signals (NESs) of the IDV NS2 protein. Surprisingly, three separate NES regions were found to contribute to the nuclear export of an eGFP fusion protein. Alanine scanning mutagenesis identified critical amino acid residues within each NES, and co-immunoprecipitation experiments demonstrated that their nuclear export activities depend on the CRM1-mediated pathway, particularly for the third NES (136-146aa) of IDV NS2. Interestingly, the third NES was important for the interaction of NS2 protein with CRM1. The findings in this study contribute to the understanding of IDV NS2 protein’s role during nucleocytoplasmic transport of influenza viral ribonucleoprotein complexes (vRNPs) and will also facilitate the development of novel anti-influenza drugs targeting nuclear export signals of IDV NS2 protein. Full article
(This article belongs to the Special Issue Non-A Influenza 2.0)
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