Point-Counterpoint: Role of Rapid Immunochromatographic Antigen Testing in Diagnosis of Influenza A Virus 2009 H1N1 Infection

Nucleic acid aptamers are generally accepted as promising elements for the specific and high-affinity binding of various biomolecules. It has been shown for a number of aptamers that the complexes with several related proteins may possess a similar affinity. An outstanding example is the G-quadruplex DNA aptamer RHA0385, which binds to the hemagglutinins of various influenza A virus strains. These hemagglutinins have homologous tertiary structures but moderate-to-low amino acid sequence identities. Here, the experiment was inverted, targeting the same protein using a set of related, parallel G-quadruplexes. The 5′- and 3′-flanking sequences of RHA0385 were truncated to yield parallel G-quadruplex with three propeller loops that were 7, 1, and 1 nucleotides in length. Next, a set of minimal, parallel G-quadruplexes with three single-nucleotide loops was tested. These G-quadruplexes were characterized both structurally and functionally. All parallel G-quadruplexes had affinities for both recombinant hemagglutinin and influenza virions. In summary, the parallel G-quadruplex represents a minimal core structure with functional activity that binds influenza A hemagglutinin. The flanking sequences and loops represent additional features that can be used to modulate the affinity. Thus, the RHA0385–hemagglutinin complex serves as an excellent example of the hypothesis of a core structure that is decorated with additional recognizing elements capable of improving the binding properties of the aptamer.

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Thapsigargin Is a Broad-Spectrum Inhibitor of Major Human Respiratory Viruses: Coronavirus, Respiratory Syncytial Virus and Influenza A Virus

Viruses ◽

10.3390/v13020234 ◽

2021 ◽

Vol 13 (2) ◽

pp. 234

Author(s):

Sarah Al-Beltagi ◽

Cristian Alexandru Preda ◽

Leah V. Goulding ◽

Joe James ◽

Juan Pu ◽

...

Keyword(s):

Influenza Virus ◽

Respiratory Syncytial Virus ◽

Influenza A Virus ◽

Broad Spectrum ◽

Influenza A ◽

Respiratory Viruses ◽

Influenza Viruses ◽

Virus Challenge ◽

2009 H1n1 ◽

Syncytial Virus

The long-term control strategy of SARS-CoV-2 and other major respiratory viruses needs to include antivirals to treat acute infections, in addition to the judicious use of effective vaccines. Whilst COVID-19 vaccines are being rolled out for mass vaccination, the modest number of antivirals in use or development for any disease bears testament to the challenges of antiviral development. We recently showed that non-cytotoxic levels of thapsigargin (TG), an inhibitor of the sarcoplasmic/endoplasmic reticulum (ER) Ca2+ ATPase pump, induces a potent host innate immune antiviral response that blocks influenza A virus replication. Here we show that TG is also highly effective in blocking the replication of respiratory syncytial virus (RSV), common cold coronavirus OC43, SARS-CoV-2 and influenza A virus in immortalized or primary human cells. TG’s antiviral performance was significantly better than remdesivir and ribavirin in their respective inhibition of OC43 and RSV. Notably, TG was just as inhibitory to coronaviruses (OC43 and SARS-CoV-2) and influenza viruses (USSR H1N1 and pdm 2009 H1N1) in separate infections as in co-infections. Post-infection oral gavage of acid-stable TG protected mice against a lethal influenza virus challenge. Together with its ability to inhibit the different viruses before or during active infection, and with an antiviral duration of at least 48 h post-TG exposure, we propose that TG (or its derivatives) is a promising broad-spectrum inhibitor against SARS-CoV-2, OC43, RSV and influenza virus.

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MC1568 inhibits HDAC6/8 activity and influenza A virus replication in lung epithelial cells: role of Hsp90 acetylation

Future Medicinal Chemistry ◽

10.4155/fmc-2016-0073 ◽

2016 ◽

Vol 8 (17) ◽

pp. 2017-2031 ◽

Cited By ~ 16

Author(s):

Simona Panella ◽

Maria Elena Marcocci ◽

Ignacio Celestino ◽

Sergio Valente ◽

Clemens Zwergel ◽

...

Keyword(s):

Epithelial Cells ◽

Influenza A Virus ◽

Virus Replication ◽

Influenza A ◽

Lung Epithelial Cells ◽

Lung Epithelial

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Host-cell dependent role of phosphorylated keratin 8 during influenza A/NWS/33 virus (H1N1) infection in mammalian cells

Virus Research ◽

10.1016/j.virusres.2021.198333 ◽

2021 ◽

Vol 295 ◽

pp. 198333

Author(s):

Flora De Conto ◽

Francesca Conversano ◽

Sergey V. Razin ◽

Silvana Belletti ◽

Maria Cristina Arcangeletti ◽

...

Keyword(s):

Host Cell ◽

Mammalian Cells ◽

Influenza A ◽

Virus H1n1 ◽

H1n1 Infection ◽

Keratin 8

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The role of host cell Rab GTPases in influenza A virus infections

Future Microbiology ◽

10.2217/fmb-2020-0092 ◽

2021 ◽

Author(s):

Jing Wu ◽

Jiaqi Gu ◽

Li Shen ◽

Xiaonan Jia ◽

Yiqian Yin ◽

...

Keyword(s):

Influenza A Virus ◽

Influenza A ◽

Respiratory Infections ◽

Small Gtpase ◽

Regulatory Mechanisms ◽

Rab Proteins ◽

Rab Gtpases ◽

Virus Infections ◽

Adaptation Mechanisms

Influenza A virus (IAV) is a crucial cause of respiratory infections in humans worldwide. Therefore, studies should clarify adaptation mechanisms of IAV and critical factors of the viral pathogenesis in human hosts. GTPases of the Rab family are the largest branch of the Ras-like small GTPase superfamily, and they regulate almost every step during vesicle-mediated trafficking. Evidence has shown that Rab proteins participate in the lifecycle of IAV. In this mini-review, we outline the regulatory mechanisms of different Rab proteins in the lifecycle of IAV. Understanding the role of Rab proteins in IAV infections is important to develop broad-spectrum host-targeted antiviral strategies.

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Role of the chaperone protein 14-3-3ε in the regulation of influenza A virus-activated beta interferon

Journal of Virology ◽

10.1128/jvi.00231-21 ◽

2021 ◽

Author(s):

Ee-Hong Tam ◽

Yen-Chin Liu ◽

Chian-Huey Woung ◽

Helene Minyi Liu ◽

Guan-Hong Wu ◽

...

Keyword(s):

Virus Infection ◽

Influenza A Virus ◽

Influenza A ◽

Critical Role ◽

Type I ◽

Type I Ifn ◽

Ns1 Protein ◽

Chaperone Protein ◽

Influenza A Virus Infection

The NS1 protein of the influenza A virus plays a critical role in regulating several biological processes in cells, including the type I interferon (IFN) response. We previously profiled the cellular factors that interact with the NS1 protein of influenza A virus and found that the NS1 protein interacts with proteins involved in RNA splicing/processing, cell cycle regulation, and protein targeting processes, including 14-3-3ε. Since 14-3-3ε plays an important role in RIG-I translocation to MAVS to activate type I IFN expression, the interaction of the NS1 and 14-3-3ε proteins may prevent the RIG-I-mediated IFN response. In this study, we confirmed that the 14-3-3ε protein interacts with the N-terminal domain of the NS1 protein and that the NS1 protein inhibits RIG-I-mediated IFN-β promoter activation in 14-3-3ε-overexpressing cells. In addition, our results showed that knocking down 14-3-3ε can reduce IFN-β expression elicited by influenza A virus and enhance viral replication. Furthermore, we found that threonine in the 49 th amino acid position of the NS1 protein plays a role in the interaction with 14-3-3ε. Influenza A virus expressing C-terminus-truncated NS1 with T49A mutation dramatically increases IFN-β mRNA in infected cells and causes slower replication than that of virus without the T-to-A mutation. Collectively, this study demonstrates that 14-3-3ε is involved in influenza A virus-initiated IFN-β expression and that the interaction of the NS1 protein and 14-3-3ε may be one of the mechanisms for inhibiting type I IFN activation during influenza A virus infection. IMPORTANCE Influenza A virus is an important human pathogen causing severe respiratory disease. The virus has evolved several strategies to dysregulate the innate immune response and facilitate its replication. We demonstrate that the NS1 protein of influenza A virus interacts with the cellular chaperone protein 14-3-3ε, which plays a critical role in RIG-I translocation that induces type I IFN expression, and that NS1 protein prevents RIG-I translocation to mitochondrial membrane. The interaction site for 14-3-3ε is the RNA-binding domain (RBD) of the NS1 protein. Therefore, this research elucidates a novel mechanism by which the NS1 RBD mediates IFN-β suppression to facilitate influenza A viral replication. Additionally, the findings reveal the antiviral role of 14-3-3ε during influenza A virus infection.

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Defense against Influenza A Virus Infection: Essential Role of the Chemokine System

Immunobiology ◽

10.1078/0171-2985-00099 ◽

2001 ◽

Vol 204 (5) ◽

pp. 603-613 ◽

Cited By ~ 60

Author(s):

A KAUFMANN

Keyword(s):

Virus Infection ◽

Influenza A Virus ◽

Influenza A ◽

Essential Role ◽

Influenza A Virus Infection

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Molecular Events Involved in Influenza A Virus-Induced Cell Death

Frontiers in Microbiology ◽

10.3389/fmicb.2021.797789 ◽

2022 ◽

Vol 12 ◽

Author(s):

Rui Gui ◽

Quanjiao Chen

Keyword(s):

Cell Death ◽

Influenza A Virus ◽

Influenza A ◽

Regulatory Networks ◽

Molecular Mechanisms ◽

Tissue Destruction ◽

Inflammatory Reactions ◽

Molecular Events ◽

Host Death

Viral infection usually leads to cell death. Moderate cell death is a protective innate immune response. By contrast, excessive, uncontrolled cell death causes tissue destruction, cytokine storm, or even host death. Thus, the struggle between the host and virus determines whether the host survives. Influenza A virus (IAV) infection in humans can lead to unbridled hyper-inflammatory reactions and cause serious illnesses and even death. A full understanding of the molecular mechanisms and regulatory networks through which IAVs induce cell death could facilitate the development of more effective antiviral treatments. In this review, we discuss current progress in research on cell death induced by IAV infection and evaluate the role of cell death in IAV replication and disease prognosis.

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