scholarly journals Widespread Historical Contingency in Influenza Viruses

2016 ◽  
Author(s):  
Jean Claude Nshogozabahizi ◽  
Jonathan Dench ◽  
Stéphane Aris-Brosou

AbstractIn systems biology and genomics, epistasis characterizes the impact that a substitution at a particular location in a genome can have on a substitution at another location. This phenomenon is often implicated in the evolution of drug resistance or to explain why particular ‘disease-causing’ mutations do not have the same outcome in all individuals. Hence, uncovering these mutations and their locations in a genome is a central question in biology. However, epistasis is notoriously difficult to uncover, especially in fast-evolving organisms. Here, we present a novel statistical approach that replies on a model developed in ecology and that we adapt to analyze genetic data in fast-evolving systems such as the influenza A virus. We validate the approach using a two-pronged strategy: extensive simulations demonstrate a low-to-moderate sensitivity with excellent specificity and precision, while analyses of experimentally-validated data recover known interactions, including in a eukaryotic system. We further evaluate the ability of our approach to detect correlated evolution during antigenic shifts or at the emergence of drug resistance. We show that in all cases, correlated evolution is prevalent in influenza A viruses, involving many pairs of sites linked together in chains, a hallmark of historical contingency. Strikingly, interacting sites are separated by large physical distances, which entails either long-range conformational changes or functional tradeoffs, for which we find support with the emergence of drug resistance. Our work paves a new way for the unbiased detection of epistasis in a wide range of organisms by performing whole-genome scans.

Viruses ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 528
Author(s):  
Brenda Aline Maya-Badillo ◽  
Rafael Ojeda-Flores ◽  
Andrea Chaves ◽  
Saul Reveles-Félix ◽  
Guillermo Orta-Pineda ◽  
...  

Influenza, a zoonosis caused by various influenza A virus subtypes, affects a wide range of species, including humans. Pig cells express both sialyl-α-2,3-Gal and sialyl-α-2,6-Gal receptors, which make them susceptible to infection by avian and human viruses, respectively. To date, it is not known whether wild pigs in Mexico are affected by influenza virus subtypes, nor whether this would make them a potential risk of influenza transmission to humans. In this work, 61 hogs from two municipalities in Campeche, Mexico, were sampled. Hemagglutination inhibition assays were performed in 61 serum samples, and positive results were found for human H1N1 (11.47%), swine H1N1 (8.19%), and avian H5N2 (1.63%) virus variants. qRT-PCR assays were performed on the nasal swab, tracheal, and lung samples, and 19.67% of all hogs were positive to these assays. An avian H5N2 virus, first reported in 1994, was identified by sequencing. Our results demonstrate that wild pigs are participating in the exposure, transmission, maintenance, and possible diversification of influenza viruses in fragmented habitats, highlighting the synanthropic behavior of this species, which has been poorly studied in Mexico.


2015 ◽  
Vol 22 (8) ◽  
pp. 957-964 ◽  
Author(s):  
Karen L. Laurie ◽  
Othmar G. Engelhardt ◽  
John Wood ◽  
Alan Heath ◽  
Jacqueline M. Katz ◽  
...  

ABSTRACTThe microneutralization assay is commonly used to detect antibodies to influenza virus, and multiple protocols are used worldwide. These protocols differ in the incubation time of the assay as well as in the order of specific steps, and even within protocols there are often further adjustments in individual laboratories. The impact these protocol variations have on influenza serology data is unclear. Thus, a laboratory comparison of the 2-day enzyme-linked immunosorbent assay (ELISA) and 3-day hemagglutination (HA) microneutralization (MN) protocols, using A(H1N1)pdm09, A(H3N2), and A(H5N1) viruses, was performed by the CONSISE Laboratory Working Group. Individual laboratories performed both assay protocols, on multiple occasions, using different serum panels. Thirteen laboratories from around the world participated. Within each laboratory, serum sample titers for the different assay protocols were compared between assays to determine the sensitivity of each assay and were compared between replicates to assess the reproducibility of each protocol for each laboratory. There was good correlation of the results obtained using the two assay protocols in most laboratories, indicating that these assays may be interchangeable for detecting antibodies to the influenza A viruses included in this study. Importantly, participating laboratories have aligned their methodologies to the CONSISE consensus 2-day ELISA and 3-day HA MN assay protocols to enable better correlation of these assays in the future.


The only direct evidence for transmission of influenza viruses between species comes from studies on swine influenza viruses. Antigenically and genetically identical Hsw1N1 influenza viruses were isolated from pigs and man on the same farm in Wisconsin, U.S.A. The isolation of H3N2 influenza viruses from a wide range of lower animals and birds suggests that influenza viruses of man can spread to the lower orders. Under some conditions the H3N2 viruses can persist for a number of years in some species. The isolation, from aquatic birds, of a large number of influenza A viruses that possess surface proteins antigenically similar to the viruses isolated from man, pigs and horses provides indirect evidence for inter-species transmission. There is now a considerable body of evidence which suggests that influenza viruses of lower animals and birds may play a role in the origin of some of the pandemic strains of influenza A viruses. There is no direct evidence that the influenza viruses in aquatic birds are transmitted to man, but they may serve as a genetic pool from which some genes may be introduced into humans by recombination. Preliminary evidence suggests that the molecular basis of host range and virulence may be related to the RNA segments coding for one of the polymerase proteins (P3) and for the nucleoprotein (NP).


2012 ◽  
Vol 93 (10) ◽  
pp. 2204-2214 ◽  
Author(s):  
Lindomar Pena ◽  
Amy L. Vincent ◽  
Crystal L. Loving ◽  
Jamie N. Henningson ◽  
Kelly M. Lager ◽  
...  

The PB1-F2 protein of the influenza A viruses (IAVs) can act as a virulence factor in mice. Its contribution to the virulence of IAV in swine, however, remains largely unexplored. In this study, we chose two genetically related H3N2 triple-reassortant IAVs to assess the impact of PB1-F2 in virus replication and virulence in pigs. Using reverse genetics, we disrupted the PB1-F2 ORF of A/swine/Wisconsin/14094/99 (H3N2) (Sw/99) and A/turkey/Ohio/313053/04 (H3N2) (Ty/04). Removing the PB1-F2 ORF led to increased expression of PB1-N40 in a strain-dependent manner. Ablation of the PB1-F2 ORF (or incorporation of the N66S mutation in the PB1-F2 ORF, Sw/99 N66S) affected the replication in porcine alveolar macrophages of only the Sw/99 KO (PB1-F2 knockout) and Sw/99 N66S variants. The Ty/04 KO strain showed decreased virus replication in swine respiratory explants, whereas no such effect was observed in Sw/99 KO, compared with the wild-type (WT) counterparts. In pigs, PB1-F2 did not affect virus shedding or viral load in the lungs for any of these strains. Upon necropsy, PB1-F2 had no effect on the lung pathology caused by Sw/99 variants. Interestingly, the Ty/04 KO-infected pigs showed significantly increased lung pathology at 3 days post-infection compared with pigs infected with the Ty/04 WT strain. In addition, the pulmonary levels of interleukin (IL)-6, IL-8 and gamma interferon were regulated differentially by the expression of PB1-F2. Taken together, these results indicate that PB1-F2 modulates virus replication, virulence and innate immune responses in pigs in a strain-dependent fashion.


2011 ◽  
Vol 32 (1) ◽  
pp. 26
Author(s):  
Aeron C Hurt

Two classes of anti-influenza drugs are currently available for the treatment or prophylaxis of influenza. These are the adamantanes (amantadine and rimantadine), which block the activity of the M2 ion channel of influenza A viruses (but not influenza B viruses), and the neuraminidase inhibitors (NAIs), which act by binding to the enzymatic site of the influenza neuraminidase (NA) thereby preventing progeny virions from being released from the host cell during viral replication. Antiviral resistance can occur in influenza viruses and render the drug ineffective for the treatment of patients. Virtually all influenza A viruses currently circulating in the human population are resistant to the adamantanes, while in comparison these viruses remain susceptible to the NAIs. In particular, very low NAI resistance has been observed in pandemic A(H1N1) 2009 viruses, even though unprecedented amounts of these drugs were used.


2020 ◽  
Vol 36 (10) ◽  
pp. 3251-3253 ◽  
Author(s):  
Congyu Lu ◽  
Zena Cai ◽  
Yuanqiang Zou ◽  
Zheng Zhang ◽  
Wenjun Chen ◽  
...  

Abstract Motivation Newly emerging influenza viruses keep challenging global public health. To evaluate the potential risk of the viruses, it is critical to rapidly determine the phenotypes of the viruses, including the antigenicity, host, virulence and drug resistance. Results Here, we built FluPhenotype, a one-stop platform to rapidly determinate the phenotypes of the influenza A viruses. The input of FluPhenotype is the complete or partial genomic/protein sequences of the influenza A viruses. The output presents five types of information about the viruses: (i) sequence annotation including the gene and protein names as well as the open reading frames, (ii) potential hosts and human-adaptation-associated amino acid markers, (iii) antigenic and genetic relationships with the vaccine strains of different HA subtypes, (iv) mammalian virulence-related amino acid markers and (v) drug resistance-related amino acid markers. FluPhenotype will be a useful bioinformatic tool for surveillance and early warnings of the newly emerging influenza A viruses. Availability and implementation It is publicly available from: http://www.computationalbiology.cn : 18888/IVEW. Supplementary information Supplementary data are available at Bioinformatics online.


2019 ◽  
Vol 147 ◽  
Author(s):  
Jiajun Yang ◽  
Hao Li ◽  
Liyuan Jia ◽  
Xianchun Lan ◽  
Yuhui Zhao ◽  
...  

Abstract In the human population, influenza A viruses are associated with acute respiratory illness and are responsible for millions of deaths annually. Avian and human influenza viruses typically have a different α2-3- and α2-6-linked sialic acid (SA) binding preference. Only a few amino acid changes in the haemagglutinin on the surface of avian influenza viruses (AIV) can cause a switch from avian to human receptor specificity, and the individuals with pathognostic chronic diseases might be more susceptible to AIV due to the decreased expression level of terminal α2-3-linked SA in their saliva. Here, using lectin and virus histochemical staining, we observed the higher expression levels of α2-3/6-linked SA influenza virus receptors in the airway of HBV-transgenic mice compared with that of control mice due to the significant decrease in control mice during ageing, which imply that this is also a risk factor for individuals with pathognostic chronic diseases susceptible to influenza viruses. Our findings will help understand the impact on influenza virus pathogenesis and transmission.


Viruses ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1028 ◽  
Author(s):  
Kevin M. Coombs ◽  
Philippe F. Simon ◽  
Nigel J. McLeish ◽  
Ali Zahedi-Amiri ◽  
Darwyn Kobasa

Influenza A viruses (IAVs) are important animal and human emerging and re-emerging pathogens that are responsible for yearly seasonal epidemics and sporadic pandemics. IAVs cause a wide range of clinical illnesses, from relatively mild infections by seasonal strains, to acute respiratory distress during infections with highly pathogenic avian IAVs (HPAI). For this study, we infected A549 human lung cells with lab prototype A/PR/8/34 (H1N1) (PR8), a seasonal H1N1 (RV733), the 2009 pandemic H1N1 (pdm09), or with two avian strains, an H5N1 HPAI strain or an H7N9 strain that has low pathogenicity in birds but high pathogenicity in humans. We used a newly-developed aptamer-based multiplexed technique (SOMAscan®) to examine >1300 human lung cell proteins affected by the different IAV strains, and identified more than 500 significantly dysregulated cellular proteins. Our analyses indicated that the avian strains induced more profound changes in the A549 global proteome compared to all tested low-pathogenicity H1N1 strains. The PR8 strain induced a general activation, primarily by upregulating many immune molecules, the seasonal RV733 and pdm09 strains had minimal effect upon assayed molecules, and the avian strains induced significant downregulation, primarily in antimicrobial response, cardiovascular and post-translational modification systems.


Pathogens ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 1320
Author(s):  
Jin Zhao ◽  
Wanting He ◽  
Meng Lu ◽  
Haijian He ◽  
Alexander Lai

Cats are susceptible to a wide range of influenza A viruses (IAV). Furthermore, cats can serve as an intermediate host, and transfer avian influenza virus (AIV) H7N2 to a veterinarian. In this report, a novel reassortant influenza virus, designated A/feline/Jiangsu/HWT/2017 (H3N2), and abbreviated as FIV-HWT-2017, was isolated from nasal swab of a symptomatic cat in Jiangsu province, China. Sequence analysis indicated that, whilst the other seven genes were most similar to the avian-origin canine influenza viruses (CIV H3N2) isolated in China, the NS gene was more closely related to the circulating human influenza virus (H3N2) in the region. Therefore, FIV-HWT-2017 is a reassortant virus. In addition, some mutations were identified, and they were similar to a distinctive CIV H3N2 clade. Whether these cats were infected with the reassortant virus was unknown, however, this random isolation of a reassortant virus indicated that domestic or stray cats were “mixing vessel” for IAV cannot be ruled out. An enhanced surveillance for novel influenza virus should include pet and stray cats.


Author(s):  
Christine H T Bui ◽  
H W Yeung ◽  
John C W Ho ◽  
Connie Y H Leung ◽  
Kenrie P Y Hui ◽  
...  

Abstract Background Human spillovers of SARS-CoV-2 to dogs and the emergence of a highly contagious avian-origin H3N2 canine influenza virus have raised concerns towards the role of dogs in the spread of SARS-CoV-2 and their susceptibility to existing human and avian influenza viruses which might result in further reassortment. Methods We systematically studied the replication kinetics of SARS-CoV-2, SARS-CoV, influenza A viruses of H1, H3, H5, H7 and H9 subtypes and influenza B viruses of Yamagata-like and Victoria-like lineages in ex-vivo canine nasal cavity (NC), soft palate (SP), trachea (T) and lung (L) tissue explant cultures and examined ACE2 and sialic acid (SA) receptor distribution in these tissues. Results There was limited productive replication of SARS-CoV-2 in canine NC and SARS-CoV in canine NC, SP and L with unexpectedly high ACE2 levels in canine NC and SP. Meanwhile, the canine tissues were susceptible to a wide range of human and avian influenza viruses, which matched with the abundance of both human and avian SA receptors. Conclusions Existence of suitable receptors and tropism for the same tissue foster virus adaptation and reassortment. Continuous surveillance in dog populations should be conducted given the plenty of chances for spillover during outbreaks.


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