Filamentous versus Spherical Morphology: A Case Study of the Recombinant A/WSN/33 (H1N1) Virus

2020 ◽  
Vol 26 (2) ◽  
pp. 297-309 ◽  
Author(s):  
Larisa V. Kordyukova ◽  
Ramil R. Mintaev ◽  
Artyom A. Rtishchev ◽  
Marina S. Kunda ◽  
Natalia N. Ryzhova ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Structural Effect ◽  
Spectrometric Analysis ◽  
Spherical Morphology ◽  
Next Generation Sequencing Ngs ◽  
Cellular Components ◽  
Negative Staining Electron Microscopy ◽  
Allantoic Cavity

AbstractInfluenza A virus is a serious human pathogen that assembles enveloped virions on the plasma membrane of the host cell. The pleiomorphic morphology of influenza A virus, represented by spherical, elongated, or filamentous particles, is important for the spread of the virus in nature. Using fixative protocols for sample preparation and negative staining electron microscopy, we found that the recombinant A/WSN/33 (H1N1) (rWSN) virus, a strain considered to be strictly spherical, may produce filamentous particles when amplified in the allantoic cavity of chicken embryos. In contrast, the laboratory WSN strain and the rWSN virus amplified in Madin–Darby canine kidney cells exhibited a spherical morphology. Next-generation sequencing (NGS) suggested a rare Ser126Cys substitution in the M1 protein of rWSN, which was confirmed by the mass spectrometric analysis. No structurally relevant substitutions were found by NGS in other proteins of rWSN. Bioinformatics algorithms predicted a neutral structural effect of the Ser126Cys mutation. The mrWSN_M1_126S virus generated after the introduction of the reverse Cys126Ser substitution exhibited a similar host-dependent partially filamentous phenotype. We hypothesize that a shortage of some as-yet-undefined cellular components involved in virion budding and membrane scission may result in the appearance of filamentous particles in the case of usually “nonfilamentous” virus strains.

scholarly journals HDAC6 Restricts Influenza A Virus by Deacetylation of the RNA Polymerase PA Subunit

2018 ◽  
Vol 93 (4) ◽  
Author(s):  
Huan Chen ◽  
Yingjuan Qian ◽  
Xin Chen ◽  
Zhiyang Ruan ◽  
Yuetian Ye ◽  
...  
Keyword(s):  
Life Cycle ◽  
Rna Polymerase ◽  
Influenza A Virus ◽  
Influenza A ◽  
Molecular Mechanisms ◽  
Polymerase Activity ◽  
Negative Regulator ◽  
Host Protein ◽  
Spectrometric Analysis ◽  
Rna Polymerase Activity

ABSTRACT The life cycle of influenza A virus (IAV) is modulated by various cellular host factors. Although previous studies indicated that IAV infection is controlled by HDAC6, the deacetylase involved in the regulation of PA remained unknown. Here, we demonstrate that HDAC6 acts as a negative regulator of IAV infection by destabilizing PA. HDAC6 binds to and deacetylates PA, thereby promoting the proteasomal degradation of PA. Based on mass spectrometric analysis, Lys(664) of PA can be deacetylated by HDAC6, and the residue is crucial for PA protein stability. The deacetylase activity of HDAC6 is required for anti-IAV activity, because IAV infection was enhanced due to elevated IAV RNA polymerase activity upon HDAC6 depletion and an HDAC6 deacetylase dead mutant (HDAC6-DM; H216A, H611A). Finally, we also demonstrate that overexpression of HDAC6 suppresses IAV RNA polymerase activity, but HDAC6-DM does not. Taken together, our findings provide initial evidence that HDAC6 plays a negative role in IAV RNA polymerase activity by deacetylating PA and thus restricts IAV RNA transcription and replication. IMPORTANCE Influenza A virus (IAV) continues to threaten global public health due to drug resistance and the emergence of frequently mutated strains. Thus, it is critical to find new strategies to control IAV infection. Here, we discover one host protein, HDAC6, that can inhibit viral RNA polymerase activity by deacetylating PA and thus suppresses virus RNA replication and transcription. Previously, it was reported that IAV can utilize the HDAC6-dependent aggresome formation mechanism to promote virus uncoating, but HDAC6-mediated deacetylation of α-tubulin inhibits viral protein trafficking at late stages of the virus life cycle. These findings together will contribute to a better understanding of the role of HDAC6 in regulating IAV infection. Understanding the molecular mechanisms of HDAC6 at various periods of viral infection may illuminate novel strategies for developing antiviral drugs.

Matrix proteins of enveloped viruses: a case study of Influenza A virus M1 protein

2018 ◽  
Vol 37 (3) ◽  
pp. 671-690 ◽  
Author(s):  
Larisa V. Kordyukova ◽  
Eleonora V. Shtykova ◽  
Lyudmila A. Baratova ◽  
Dmitri I. Svergun ◽  
Oleg V. Batishchev
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Matrix Proteins ◽  
Enveloped Viruses ◽  
M1 Protein

scholarly journals Host factor Rab11a is critical for efficient assembly of influenza A virus genomic segments

2021 ◽  
Vol 17 (5) ◽  
pp. e1009517
Author(s):  
Julianna Han ◽  
Ketaki Ganti ◽  
Veeresh Kumar Sali ◽  
Carly Twigg ◽  
Yifeng Zhang ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Genome Assembly ◽  
Influenza A ◽  
Early Time ◽  
Virus Genome ◽  
Host Factor ◽  
Influenza A Viruses ◽  
Ribonucleoprotein Complexes ◽  
Microtubule Networks ◽  
Cellular Components

It is well documented that influenza A viruses selectively package 8 distinct viral ribonucleoprotein complexes (vRNPs) into each virion; however, the role of host factors in genome assembly is not completely understood. To evaluate the significance of cellular factors in genome assembly, we generated a reporter virus carrying a tetracysteine tag in the NP gene (NP-Tc virus) and assessed the dynamics of vRNP localization with cellular components by fluorescence microscopy. At early time points, vRNP complexes were preferentially exported to the MTOC; subsequently, vRNPs associated on vesicles positive for cellular factor Rab11a and formed distinct vRNP bundles that trafficked to the plasma membrane on microtubule networks. In Rab11a deficient cells, however, vRNP bundles were smaller in the cytoplasm with less co-localization between different vRNP segments. Furthermore, Rab11a deficiency increased the production of non-infectious particles with higher RNA copy number to PFU ratios, indicative of defects in specific genome assembly. These results indicate that Rab11a+ vesicles serve as hubs for the congregation of vRNP complexes and enable specific genome assembly through vRNP:vRNP interactions, revealing the importance of Rab11a as a critical host factor for influenza A virus genome assembly.

scholarly journals Case Study: A 24-Year-Old Female Got Co-Infection with New Corona Virus Pneumonia and Influenza A Virus

2020 ◽  
Vol 6 (2) ◽  
Author(s):  
Dong Xin ◽  
Liu Xiuyun ◽  
Xie Xingjia ◽  
Liu Longfei ◽  
Wang Jun ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Corona Virus ◽  
Virus Pneumonia

Mass Spectrometric Analysis of S-palmitoylation of Hemagglutinin from Influenza A Virus

2016 ◽  
Vol 44 (10) ◽  
pp. 1521-1527 ◽  
Author(s):  
Zi-Jian WANG ◽  
Xiang GAO ◽  
Jing-Bo YANG ◽  
Wan-Chun SUN ◽  
Dong-Lin WU ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Mass Spectrometric ◽  
Mass Spectrometric Analysis ◽  
Spectrometric Analysis

scholarly journals Host Factor Rab11a is Critical for Efficient Assembly of Influenza A Virus Genomic Segments

2021 ◽  
Author(s):  
Julianna Han ◽  
Ketaki Ganti ◽  
Veeresh Kumar Sali ◽  
Carly Twigg ◽  
Yifeng Zhang ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Genome Assembly ◽  
Influenza A ◽  
Early Time ◽  
Virus Genome ◽  
Host Factor ◽  
Influenza A Viruses ◽  
Ribonucleoprotein Complexes ◽  
Microtubule Networks ◽  
Cellular Components

It is well documented that influenza A viruses selectively package 8 distinct viral ribonucleoprotein complexes (vRNPs) into each virion; however, the role of host factors in genome assembly is not completely understood. To evaluate the significance of cellular factors in genome assembly, we generated a reporter virus carrying a tetracysteine tag in the NP gene (NP-Tc virus) and assessed the dynamics of vRNP localization with cellular components by fluorescence microscopy. At early time points, vRNP complexes were preferentially exported to the MTOC; subsequently, vRNPs associated on vesicles positive for cellular factor Rab11a and formed distinct vRNP bundles that trafficked to the plasma membrane on microtubule networks. In Rab11a deficient cells, however, vRNP bundles were smaller in the cytoplasm with less co-localization between different vRNP segments. Furthermore, Rab11a deficiency increased the production of non-infectious particles with higher RNA copy number to PFU ratios, indicative of defects in specific genome assembly. These results indicate that Rab11a+ vesicles serve as hubs for the congregation of vRNP complexes and enable specific genome assembly through vRNP:vRNP interactions, revealing the importance of Rab11a as a critical host factor for influenza A virus genome assembly.

scholarly journals Simvastatin modulates cellular components in influenza A virus-infected cells

2014 ◽  
Vol 34 (1) ◽  
pp. 61-73 ◽  
Author(s):  
PARVANEH MEHRBOD ◽  
MOHD HAIR-BEJO ◽  
TENGKU AZMI TENGKU IBRAHIM ◽  
ABDUL RAHMAN OMAR ◽  
MOHAMED EL ZOWALATY ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Infected Cells ◽  
Cellular Components

scholarly journals Ribosomal frameshifting used in influenza A virus expression occurs within the sequence UCC_UUU_CGU and is in the +1 direction

Open Biology ◽  
2012 ◽  
Vol 2 (10) ◽  
pp. 120109 ◽  
Author(s):  
A. E. Firth ◽  
B. W. Jagger ◽  
H. M. Wise ◽  
C. C. Nelson ◽  
K. Parsawar ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Mass Spectrometric ◽  
Spectrometric Analysis ◽  
Ribosomal Frameshifting ◽  
Reading Frame ◽  
New Class ◽  
Cellular Genes ◽  
Virus Expression ◽  
Paralysis Virus

Programmed ribosomal frameshifting is used in the expression of many virus genes and some cellular genes. In eukaryotic systems, the most well-characterized mechanism involves –1 tandem tRNA slippage on an X_XXY_YYZ motif. By contrast, the mechanisms involved in programmed +1 (or −2) slippage are more varied and often poorly characterized. Recently, a novel gene, PA-X, was discovered in influenza A virus and found to be expressed via a shift to the +1 reading frame. Here, we identify, by mass spectrometric analysis, both the site (UCC_UUU_CGU) and direction (+1) of the frameshifting that is involved in PA-X expression. Related sites are identified in other virus genes that have previously been proposed to be expressed via +1 frameshifting. As these viruses infect insects (chronic bee paralysis virus), plants (fijiviruses and amalgamaviruses) and vertebrates (influenza A virus), such motifs may form a new class of +1 frameshift-inducing sequences that are active in diverse eukaryotes.

scholarly journals Infection Dynamics of Swine Influenza Virus in a Danish Pig Herd Reveals Recurrent Infections with Different Variants of the H1N2 Swine Influenza A Virus Subtype

Viruses ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 1013
Author(s):  
Tarka Bhatta ◽  
Pia Ryt-Hansen ◽  
Jens Nielsen ◽  
Lars Larsen ◽  
Inge Larsen ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Swine Influenza Virus ◽  
Swine Influenza ◽  
Respiratory Illness ◽  
Antigenic Sites ◽  
Infection Dynamics ◽  
Next Generation Sequencing Ngs ◽  
And Control ◽  
Swine Influenza A Virus

Influenza A virus (IAV) in swine, so-called swine influenza A virus (swIAV), causes respiratory illness in pigs around the globe. In Danish pig herds, a H1N2 subtype named H1N2dk is one of the main circulating swIAV. In this cohort study, the infection dynamic of swIAV was evaluated in a Danish pig herd by sampling and PCR testing of pigs from two weeks of age until slaughter at 22 weeks of age. In addition, next generation sequencing (NGS) was used to identify and characterize the complete genome of swIAV circulating in the herd, and to examine the antigenic variability in the antigenic sites of the virus hemagglutinin (HA) and neuraminidase (NA) proteins. Overall, 76.6% of the pigs became PCR positive for swIAV during the study, with the highest prevalence at four weeks of age. Detailed analysis of the virus sequences obtained showed that the majority of mutations occurred at antigenic sites in the HA and NA proteins of the virus. At least two different H1N2 variants were found to be circulating in the herd; one H1N2 variant was circulating at the sow and nursery sites, while another H1N2 variant was circulating at the finisher site. Furthermore, it was demonstrated that individual pigs had recurrent swIAV infections with the two different H1N2 variants, but re-infection with the same H1N2 variant was also observed. Better understandings of the epidemiology, genetic and antigenic diversity of swIAV may help to design better health interventions for the prevention and control of swIAV infections in the herds.

Antiviral effect of polyphenol-enriched extract of Rumex Acetosa L. against Influenza A virus

Planta Medica ◽  
2012 ◽  
Vol 78 (11) ◽  
Author(s):  
A Derksen ◽  
W Hafezi ◽  
A Hensel ◽  
J Kühn
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Antiviral Effect ◽  
Rumex Acetosa
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