scholarly journals Influenza A Virus Neuraminidase Limits Viral Superinfection

2008 ◽  
Vol 82 (10) ◽  
pp. 4834-4843 ◽  
Author(s):  
I-Chueh Huang ◽  
Wenhui Li ◽  
Jianhua Sui ◽  
Wayne Marasco ◽  
Hyeryun Choe ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Viral Proteins ◽  
Neuraminidase Inhibitors ◽  
Influenza A Viruses ◽  
Oseltamivir Carboxylate ◽  
Enveloped Viruses ◽  
Cellular Expression ◽  
Viral Genes ◽  
H3n2 Influenza

ABSTRACT Enveloped viruses use multiple mechanisms to inhibit infection of a target cell by more than one virion. These mechanisms may be of particular importance for the evolution of segmented viruses, because superinfection exclusion may limit the frequency of reassortment of viral genes. Here, we show that cellular expression of influenza A virus neuraminidase (NA), but not hemagglutinin (HA) or the M2 proton pump, inhibits entry of HA-pseudotyped retroviruses. Cells infected with H1N1 or H3N2 influenza A virus were similarly refractory to HA-mediated infection and to superinfection with a second influenza A virus. Both HA-mediated entry and viral superinfection were rescued by the neuraminidase inhibitors oseltamivir carboxylate and zanamivir. These inhibitors also prevented the removal of α-2,3- and α-2,6-linked sialic acid observed in cells expressing NA or infected with influenza A viruses. Our data indicate that NA alone among viral proteins limits influenza A virus superinfection.

scholarly journals Unseasonal Transmission of H3N2 Influenza A Virus During the Swine-Origin H1N1 Pandemic

2010 ◽  
Vol 84 (11) ◽  
pp. 5715-5718 ◽  
Author(s):  
Elodie Ghedin ◽  
David E. Wentworth ◽  
Rebecca A. Halpin ◽  
Xudong Lin ◽  
Jayati Bera ◽  
...  
Keyword(s):  
New York ◽  
Influenza A Virus ◽  
Influenza A ◽  
New York State ◽  
The United States ◽  
Influenza Viruses ◽  
Influenza A Viruses ◽  
York State ◽  
Low Incidence ◽  
H3n2 Influenza

ABSTRACT The initial wave of swine-origin influenza A virus (pandemic H1N1/09) in the United States during the spring and summer of 2009 also resulted in an increased vigilance and sampling of seasonal influenza viruses (H1N1 and H3N2), even though they are normally characterized by very low incidence outside of the winter months. To explore the nature of virus evolution during this influenza “off-season,” we conducted a phylogenetic analysis of H1N1 and H3N2 sequences sampled during April to June 2009 in New York State. Our analysis revealed that multiple lineages of both viruses were introduced and cocirculated during this time, as is typical of influenza virus during the winter. Strikingly, however, we also found strong evidence for the presence of a large transmission chain of H3N2 viruses centered on the south-east of New York State and which continued until at least 1 June 2009. These results suggest that the unseasonal transmission of influenza A viruses may be more widespread than is usually supposed.

scholarly journals Human Cytotoxic T-Lymphocyte Repertoire to Influenza A Viruses

1998 ◽  
Vol 72 (11) ◽  
pp. 8682-8689 ◽  
Author(s):  
Julie Jameson ◽  
John Cruz ◽  
Francis A. Ennis
Keyword(s):  
Cell Line ◽  
Influenza A Virus ◽  
Cell Lines ◽  
T Lymphocyte ◽  
Influenza A ◽  
Matrix Protein ◽  
Cytotoxic T Lymphocyte ◽  
Viral Proteins ◽  
Influenza A Viruses ◽  
Nonstructural Protein 1

ABSTRACT The murine CD8+ cytotoxic-T-lymphocyte (CTL) repertoire appears to be quite limited in response to influenza A viruses. The CTL responses to influenza A virus in humans were examined to determine if the CTL repertoire is also very limited. Bulk cultures revealed that a number of virus proteins were recognized in CTL assays. CTL lines were isolated from three donors for detailed study and found to be specific for epitopes on numerous influenza A viral proteins. Eight distinct CD8+ CTL lines were isolated from donor 1. The proteins recognized by these cell lines included the nucleoprotein (NP), matrix protein (M1), nonstructural protein 1 (NS1), polymerases (PB1 and PB2), and hemagglutinin (HA). Two CD4+ cell lines, one specific for neuraminidase (NA) and the other specific for M1, were also characterized. These CTL results were confirmed by precursor frequency analysis of peptide-specific gamma interferon-producing cells detected by ELISPOT. The epitopes recognized by 6 of these 10 cell lines have not been previously described; 8 of the 10 cell lines were cross-reactive to subtype H1N1, H2N2, and H3N2 viruses, 1 cell line was cross-reactive to subtypes H1N1 and H2N2, and 1 cell line was subtype H1N1 specific. A broad CTL repertoire was detected in the two other donors, and cell lines specific for the NP, NA, HA, M1, NS1, and M2 viral proteins were isolated. These findings indicate that the human memory CTL response to influenza A virus is broadly directed to epitopes on a wide variety of proteins, unlike the limited response observed following infection of mice.

Interspecies and intraspecies transmission of influenza A viruses: viral, host and environmental factors

2010 ◽  
Vol 11 (1) ◽  
pp. 53-72 ◽  
Author(s):  
Hadi M. Yassine ◽  
Chang-Won Lee ◽  
Renukaradhya Gourapura ◽  
Yehia M. Saif
Keyword(s):  
Influenza A ◽  
Mammalian Species ◽  
Viral Proteins ◽  
Interspecies Transmission ◽  
Influenza B ◽  
Influenza A Viruses ◽  
Enveloped Viruses ◽  
Host System ◽  
Specific Host ◽  
The Family

AbstractInfluenza A viruses are enveloped viruses belonging to the familyOrthomyxoviridaethat encompasses four more genera: Influenza B, Influenza C, Isavirus and Thogotovirus. Type A viruses belong to the only genus that is highly infectious to a variety of mammalian and avian species. They are divided into subtypes based on two surface glycoproteins, the hemagglutinin (HA) and neuraminidase (NA). So far, 16 HA and 9 NA subtypes have been identified worldwide, making a possible combination of 144 subtypes between both proteins. Generally, individual viruses are host-specific, however, interspecies transmission of influenza A viruses is not uncommon. All of the HA and NA subtypes have been isolated from wild birds; however, infections in humans and other mammalian species are limited to a few subtypes. The replication of individual influenza A virus in a specific host is dependent on many factors including, viral proteins, host system and environmental conditions. In this review, the key findings that contribute to the transmission of influenza A viruses amongst different species are summarized.

scholarly journals Nonproteolytic K29-Linked Ubiquitination of the PB2 Replication Protein of Influenza A Viruses by Proviral Cullin 4-Based E3 Ligases

mBio ◽  
2020 ◽  
Vol 11 (2) ◽  
Author(s):  
Marwah Karim ◽  
Elise Biquand ◽  
Marion Declercq ◽  
Yves Jacob ◽  
Sylvie van der Werf ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Ubiquitin Ligases ◽  
Viral Proteins ◽  
Replication Protein ◽  
E3 Ubiquitin Ligases ◽  
Influenza A Viruses ◽  
E3 Ligases ◽  
Recombinant Viruses ◽  
Virion Production

ABSTRACT The multifunctional nature of viral proteins is essentially driven by posttranslational modifications (PTMs) and is key for the successful outcome of infection. For influenza A viruses (IAVs), a composite pattern of PTMs regulates the activity of viral proteins. However, almost none are known that target the PB2 replication protein, except for inducing its degradation. We show here that PB2 undergoes a nonproteolytic ubiquitination during infection. We identified E3 ubiquitin ligases catalyzing this ubiquitination as two multicomponent RING-E3 ligases based on cullin 4 (CRL4s), which are both contributing to the levels of ubiquitinated forms of PB2 in infected cells. The CRL4 E3 ligase activity is required for the normal progression of the viral cycle and for maximal virion production, indicating that the CRL4s mediate a ubiquitin signaling that promotes infection. The CRL4s are recruiting PB2 through an unconventional bimodal interaction with both the DDB1 adaptor and DCAF substrate receptors. While able to bind to PB2 when engaged in the viral polymerase complex, the CRL4 factors do not alter transcription and replication of the viral segments during infection. CRL4 ligases catalyze different patterns of lysine ubiquitination on PB2. Recombinant viruses mutated in the targeted lysines showed attenuated viral production, suggesting that CRL4-mediated ubiquitination of PB2 contributes to IAV infection. We identified K29-linked ubiquitin chains as main components of the nonproteolytic PB2 ubiquitination mediated by the CRL4s, providing the first example of the role of this atypical ubiquitin linkage in the regulation of a viral infection. IMPORTANCE Successful infection by influenza A virus, a pathogen of major public health importance, involves fine regulation of the multiple functions of the viral proteins, which often relies on post-translational modifications (PTMs). The PB2 protein of influenza A viruses is essential for viral replication and a key determinant of host range. While PTMs of PB2 inducing its degradation have been identified, here we show that PB2 undergoes a regulating PTM signaling detected during infection, based on an atypical K29-linked ubiquitination and mediated by two multicomponent E3 ubiquitin ligases. Recombinant viruses impaired for CRL4-mediated ubiquitination are attenuated, indicating that ubiquitination of PB2 is necessary for an optimal influenza A virus infection. The CRL4 E3 ligases are required for normal viral cycle progression and for maximal virion production. Consequently, they represent potential candidate host factors for antiviral targets.

scholarly journals Introduction to molecular biology of influenza a viruses.

2014 ◽  
Vol 61 (3) ◽  
Author(s):  
Bogusław Szewczyk ◽  
Krystyna Bieńkowska-Szewczyk ◽  
Ewelina Król
Keyword(s):  
Molecular Biology ◽  
Influenza A Virus ◽  
Genome Organization ◽  
Influenza A ◽  
Current Knowledge ◽  
Viral Proteins ◽  
Influenza A Viruses ◽  
Viral Release ◽  
Virion Structure ◽  
Viral Development

This minireview presents an overview of current knowledge on virion structure, genome organization and basic events in the development of influenza A virus. The processes of entry, transcription/replication and viral release are described. In this context, the roles of viral proteins (including recently discovered minor polypeptides) in the subsequent stages of viral development are also discussed.

Influenza virus proteins as factors involved in interspecies transmission

2014 ◽  
Vol 17 (4) ◽  
Author(s):  
I.M. Góra ◽  
W. Rożek ◽  
J.F. Żmudziński
Keyword(s):  
Influenza Virus ◽  
Host Response ◽  
Influenza A ◽  
Viral Proteins ◽  
Interspecies Transmission ◽  
Influenza A Viruses ◽  
Specific Host ◽  
Viral Genes ◽  
Interspecies Barrier

AbstractInfluenza A viruses cause recurrent epidemics and global pandemics. One of the unique features of influenza virus is the ability to overcome interspecies barrier. Reassortment of viral genes and the accumulation of mutations contribute to the emergence of new influenza virus variants. The replication of influenza A virus in a specific host depends on many factors e.g. activity of viral proteins, host response system and environmental conditions. In this review the role of viral proteins as a condition for crossing the species barriers is discussed.

scholarly journals Effects of Basic Amino Acids and Their Derivatives on SARS-CoV-2 and Influenza-A Virus Infection

Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1301
Author(s):  
Ivonne Melano ◽  
Li-Lan Kuo ◽  
Yan-Chung Lo ◽  
Po-Wei Sung ◽  
Ni Tien ◽  
...  
Keyword(s):  
Amino Acids ◽  
Virus Infection ◽  
Influenza A Virus ◽  
Influenza A ◽  
Enveloped Viruses ◽  
Virus Attachment ◽  
Basic Amino Acids ◽  
Ester Derivative ◽  
Endosomal Acidification

Amino acids have been implicated with virus infection and replication. Here, we demonstrate the effects of two basic amino acids, arginine and lysine, and their ester derivatives on infection of two enveloped viruses, SARS-CoV-2, and influenza A virus. We found that lysine and its ester derivative can efficiently block infection of both viruses in vitro. Furthermore, the arginine ester derivative caused a significant boost in virus infection. Studies on their mechanism of action revealed that the compounds potentially disturb virus uncoating rather than virus attachment and endosomal acidification. Our findings suggest that lysine supplementation and the reduction of arginine-rich food intake can be considered as prophylactic and therapeutic regimens against these viruses while also providing a paradigm for the development of broad-spectrum antivirals.

scholarly journals Investigating Influenza A Virus Infection: Tools To Track Infection and Limit Tropism: TABLE 1

2015 ◽  
Vol 89 (12) ◽  
pp. 6167-6170 ◽  
Author(s):  
Jessica K. Fiege ◽  
Ryan A. Langlois
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Therapeutic Interventions ◽  
Microrna Target ◽  
Influenza A Viruses ◽  
Host Interactions ◽  
Target Sites ◽  
Recent Developments ◽  
Cellular Tropism ◽  
The Relationship

Influenza A viruses display a broad cellular tropism within the respiratory tracts of mammalian hosts. Uncovering the relationship between tropism and virus immunity, pathogenesis, and transmission will be critical for the development of therapeutic interventions. Here we discuss recent developments of several recombinant strains of influenza A virus. These viruses have inserted reporters to track tropism, microRNA target sites to restrict tropism, or barcodes to assess transmission dynamics, expanding our understanding of pathogen-host interactions.

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