Anti-lipopolysaccharide factor D from kuruma shrimp exhibits antiviral activity

AbstractAnti-lipopolysaccharide factors (ALFs) exhibit a potent antimicrobial activity against a broad range of bacteria, filamentous fungi, and viruses. In previous reports, seven groups of ALFs (groups A–G) were identified in penaeid shrimp. Among them, group D showed negative net charges and weak antimicrobial activity. Whether this group has antiviral function is not clear. In this study, the ALF sequences of penaeid shrimp were analyzed, and eight groups of ALF family (groups A–H) were identified. The four ALFs including MjALF-C2, MjALF-D1, MjALF-D2, and MjALF-E2 from kuruma shrimp Marsupenaeus japonicus were expressed recombinantly in Escherichia coli, and the antiviral activity was screened via injection of purified recombinant ALFs into shrimp following white spot syndrome virus (WSSV) infection. Results showed that the expression of Vp28 (WSSV envelope protein) decreased significantly in the MjALF-D2-injected shrimp only. Therefore, MjALF-D2 was chosen for further study. Expression pattern analysis showed that MjAlf-D2 was upregulated in shrimp challenged by WSSV. The WSSV replication was detected in RNA, genomic DNA, and protein levels using VP28 and Ie1 (immediate-early gene of WSSV) as indicators in MjALF-D2-injected shrimp following WSSV infection. Results showed that WSSV replication was significantly inhibited compared with that in the rTRX- or PBS-injected control groups. After knockdown of MjAlf-D2 in shrimp by RNA interference, the WSSV replication increased significantly in the shrimp. All these results suggested that MjALF-D2 has an antiviral function in shrimp immunity, and the recombinant ALF-D2 has a potential application for viral disease control in shrimp aquaculture.

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SUMOylation of SAMHD1 at Lysine 595 is required for HIV-1 restriction in non-cycling cells

Nature Communications ◽

10.1038/s41467-021-24802-5 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Charlotte Martinat ◽

Arthur Cormier ◽

Joëlle Tobaly-Tapiero ◽

Noé Palmic ◽

Nicoletta Casartelli ◽

...

Keyword(s):

Antiviral Activity ◽

Reverse Transcription ◽

Immune Cells ◽

Viral Restriction ◽

Antiviral Function ◽

Hiv 1 ◽

Constitutively Active

AbstractSAMHD1 is a cellular triphosphohydrolase (dNTPase) proposed to inhibit HIV-1 reverse transcription in non-cycling immune cells by limiting the supply of the dNTP substrates. Yet, phosphorylation of T592 downregulates SAMHD1 antiviral activity, but not its dNTPase function, implying that additional mechanisms contribute to viral restriction. Here, we show that SAMHD1 is SUMOylated on residue K595, a modification that relies on the presence of a proximal SUMO-interacting motif (SIM). Loss of K595 SUMOylation suppresses the restriction activity of SAMHD1, even in the context of the constitutively active phospho-ablative T592A mutant but has no impact on dNTP depletion. Conversely, the artificial fusion of SUMO2 to a non-SUMOylatable inactive SAMHD1 variant restores its antiviral function, a phenotype that is reversed by the phosphomimetic T592E mutation. Collectively, our observations clearly establish that lack of T592 phosphorylation cannot fully account for the restriction activity of SAMHD1. We find that SUMOylation of K595 is required to stimulate a dNTPase-independent antiviral activity in non-cycling immune cells, an effect that is antagonized by cyclin/CDK-dependent phosphorylation of T592 in cycling cells.

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Flavonol 7-O-Glucoside Herbacitrin Inhibits HIV-1 Replication through Simultaneous Integrase and Reverse Transcriptase Inhibition

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2019/1064793 ◽

2019 ◽

Vol 2019 ◽

pp. 1-6 ◽

Cited By ~ 3

Author(s):

Éva Áy ◽

Attila Hunyadi ◽

Mária Mezei ◽

János Minárovits ◽

Judit Hohmann

Keyword(s):

Antiviral Activity ◽

Reverse Transcriptase ◽

Cell Cultures ◽

Core Protein ◽

Integrase Inhibitor ◽

Host Cells ◽

Cytotoxic Activities ◽

Protein Levels ◽

Hiv 1 ◽

Antiretroviral Activity

Here we report the evaluation of the antiretroviral effect of two flavonoid 7-O-glucosides, herbacitrin (1) and gossypitrin (2), together with quercetin (3), a well-studied flavonol. Antiviral activity of the flavonoids was assessed by analyzing HIV-1 p24 core protein levels in the supernatants of HIV-1 infected MT-4 and MT-2 cell cultures. The compounds showed mild to weak cytotoxic activities on the host cells; herbacitrin was the strongest in this regard (CC50=27.8 and 63.64 μM on MT-4 and MT-2 cells, respectively). In nontoxic concentrations, herbacitrin and quercetin reduced HIV-1 replication, whereas gossypitrin was ineffective. Herbacitrin was found to inhibit reverse transcriptase at 21.5 μM, while it was a more potent integrase inhibitor already active at 2.15 μM. Therefore, our observations suggest that herbacitrin exerts antiretroviral activity through simultaneously acting on these two targets of HIV-1 and that integrase inhibition might play a major role in this activity.

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Identification of Feline Interferon Regulatory Factor 1 as an Efficient Antiviral Factor against the Replication of Feline Calicivirus and Other Feline Viruses

BioMed Research International ◽

10.1155/2018/2739830 ◽

2018 ◽

Vol 2018 ◽

pp. 1-10 ◽

Cited By ~ 2

Author(s):

Yongxiang Liu ◽

Xiaoxiao Liu ◽

Hongtao Kang ◽

Xiaoliang Hu ◽

Jiasen Liu ◽

...

Keyword(s):

Antiviral Activity ◽

Viral Infections ◽

Interferon Regulatory Factor ◽

Feline Calicivirus ◽

Type I ◽

Norwalk Virus ◽

Regulatory Factor ◽

Feline Panleukopenia Virus ◽

Protein Levels ◽

Interferon Regulatory Factor 1

Interferons (IFNs) can inhibit most, if not all, viral infections by eliciting the transcription of hundreds of interferon-stimulated genes (ISGs). Feline calicivirus (FCV) is a highly contagious pathogen of cats and a surrogate for Norwalk virus. Interferon efficiently inhibits the replication of FCV, but the mechanism of the antiviral activity is poorly understood. Here, we evaluated the anti-FCV activity of ten ISGs, whose antiviral activities were previously reported. The results showed that interferon regulatory factor 1 (IRF1) can significantly inhibit the replication of FCV, whereas the other ISGs tested in this study failed. Further, we found that IRF1 was localized in the nucleus and efficiently activated IFN-β and the ISRE promoter. IRF1 can trigger the production of endogenous interferon and the expression of ISGs, suggesting that IRF1 can positively regulate IFN signalling. Importantly, the mRNA and protein levels of IRF1 were reduced upon FCV infection, which may be a new strategy for FCV to evade the innate immune system. Finally, the antiviral activity of IRF1 against feline panleukopenia virus, feline herpesvirus, and feline infectious peritonitis virus was demonstrated. These data indicate that feline IRF1 plays an important role in regulating the host type I IFN response and inhibiting feline viral infections.

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Nanodroplet-Benzalkonium Chloride Formulation Demonstrates In Vitro and Ex- Vivo Broad-Spectrum Antiviral Activity Against SARS-CoV-2 and other Enveloped Viruses

10.21203/rs.3.rs-362864/v1 ◽

2021 ◽

Author(s):

Jessie Pannu ◽

Susan Ciotti ◽

Shyamala Ganesan ◽

George Arida ◽

Chad Costley ◽

...

Keyword(s):

Antiviral Activity ◽

Broad Spectrum ◽

Benzalkonium Chloride ◽

Ex Vivo ◽

Viral Disease ◽

Influenza B ◽

Human Coronavirus ◽

Enveloped Viruses ◽

Nasal Irritation

Abstract Objective: The Covid-19 pandemic has highlighted the importance of aerosolized droplets inhaled into the nose in the transmission of respiratory viral disease. Inactivating pathogenic viruses at the nasal port of entry may reduce viral loads, thereby reducing infection, transmission and spread. In this communication, we demonstrate safe and broad anti-viral activity of oil-in-water nanoemulsion (nanodroplet) formulation containing the potent antiseptic 0.13% Benzalkonium Chloride (NE-BZK). Results: We have demonstrated that NE-BZK exhibits broad-spectrum, long-lasting antiviral activity with >99.9% in vitro killing of enveloped viruses including SARS-CoV-2, human coronavirus, RSV, and influenza B. In vitro and ex-vivo studies demonstrated continued killing of >99.99% of human coronavirus with diluted NE-BZK and persistent for 8 hours post application, respectively. The repeated application of NE-BZK, twice daily for 2 weeks into rabbit nostrils demonstrated its safety with no nasal irritation. These findings demonstrate that formulating BZK into the proprietary nanodroplets offers a safe and effective antiviral and a significant addition to strategies to combat the spread of respiratory viral infectious diseases.

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Oligomerization Requirements for MX2-Mediated Suppression of HIV-1 Infection

Journal of Virology ◽

10.1128/jvi.02247-15 ◽

2015 ◽

Vol 90 (1) ◽

pp. 22-32 ◽

Cited By ~ 24

Author(s):

Matthew D. J. Dicks ◽

Caroline Goujon ◽

Darja Pollpeter ◽

Gilberto Betancor ◽

Luis Apolonia ◽

...

Keyword(s):

Antiviral Activity ◽

Structure Function ◽

Influenza A ◽

Acute Infection ◽

Higher Order ◽

Nuclear Accumulation ◽

Antiviral Function ◽

Ring Structures ◽

Hiv 1

ABSTRACTHuman myxovirus resistance 2 (MX2/MXB) is an interferon-stimulated gene (ISG) and was recently identified as a late postentry suppressor of human immunodeficiency virus type 1 (HIV-1) infection, inhibiting the nuclear accumulation of viral cDNAs. Although the HIV-1 capsid (CA) protein is believed to be the viral determinant of MX2-mediated inhibition, the precise mechanism of antiviral action remains unclear. The MX family of dynamin-like GTPases also includes MX1/MXA, a well-studied inhibitor of a range of RNA and DNA viruses, including influenza A virus (FLUAV) and hepatitis B virus but not retroviruses. MX1 and MX2 are closely related and share similar domain architectures and structures. However, MX2 possesses an extended N terminus that is essential for antiviral function and confers anti-HIV-1 activity on MX1 [MX1(NMX2)]. Higher-order oligomerization is required for the antiviral activity of MX1 against FLUAV, with current models proposing that MX1 forms ring structures that constrict around viral nucleoprotein complexes. Here, we performed structure-function studies to investigate the requirements for oligomerization of both MX2 and chimeric MX1(NMX2) for the inhibition of HIV-1 infection. The oligomerization state of mutated proteins with amino acid substitutions at multiple putative oligomerization interfaces was assessed using a combination of covalent cross-linking and coimmunoprecipitation. We show that while monomeric MX2 and MX1(NMX2) mutants are not antiviral, higher-order oligomerization does not appear to be required for full antiviral activity of either protein. We propose that lower-order oligomerization of MX2 is sufficient for the effective inhibition of HIV-1.IMPORTANCEInterferon plays an important role in the control of virus replication during acute infectionin vivo. Recently, cultured cell experiments identified human MX2 as a key effector in the interferon-mediated postentry block to HIV-1 infection. MX2 is a member of a family of large dynamin-like GTPases that includes MX1/MXA, a closely related interferon-inducible inhibitor of several viruses, including FLUAV, but not HIV-1. MX GTPases form higher-order oligomeric structures, and the oligomerization of MX1 is required for inhibitory activity against many of its viral targets. Through structure-function studies, we report that monomeric mutants of MX2 do not inhibit HIV-1. However, in contrast to MX1, oligomerization beyond dimer assembly does not seem to be required for the antiviral activity of MX2, implying that fundamental differences exist between the antiviral mechanisms employed by these closely related proteins.

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Lead Aggravates Viral Disease and Represses the Antiviral Activity of Interferon Inducers

Environmental Health Perspectives ◽

10.1289/ehp.747113 ◽

1974 ◽

Vol 7 ◽

pp. 113-119 ◽

Cited By ~ 39

Author(s):

Joseph H. Gainer

Keyword(s):

Antiviral Activity ◽

Viral Disease ◽

Interferon Inducers

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Inhibition of human cytomegalovirus immediate-early gene expression by an antisense oligonucleotide complementary to immediate-early RNA.

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.40.9.2004 ◽

1996 ◽

Vol 40 (9) ◽

pp. 2004-2011 ◽

Cited By ~ 97

Author(s):

K P Anderson ◽

M C Fox ◽

V Brown-Driver ◽

M J Martin ◽

R F Azad

Keyword(s):

Gene Expression ◽

Cell Culture ◽

Antiviral Activity ◽

Protein Expression ◽

Human Cytomegalovirus ◽

Host Cells ◽

Early Gene ◽

Immediate Early ◽

Mrna Levels ◽

Virus Adsorption

ISIS 2922 is a phosphorothioate oligonucleotide that is complementary to human cytomegalovirus (CMV) immediate-early (IE) RNA and that exhibits potent and specific antiviral activity against CMV in cell culture assays. Specific assay systems were developed to separately characterize the antisense and nonantisense components of the antiviral activity mediated by ISIS 2922. In U373 cells transformed with cDNA encoding the CMV IE 55-kDa (IE55) protein, expression was inhibited at nanomolar concentrations comparable to effective concentrations in antiviral assays. The specificity of inhibition was demonstrated by using control oligonucleotides incorporating progressive base changes to destabilize oligonucleotide-RNA base pairing and by showing a lack of inhibition of the CMV IE72 product expressed from the same promoter. Inhibition of IE55 protein expression correlated with a reduction in mRNA levels consistent with an RNase H-mediated termination event. Studies with virus-infected cells demonstrated that antisense and nonantisense mechanisms contribute to the antiviral activity of ISIS 2922. Base complementarity to target RNA was important for optimal activity in antiviral assays, but base changes affecting parameters other than hybridization affinity also influenced antiviral activity. Sequence-independent inhibition of virus adsorption to host cells by phosphorothioate oligonucleotides was also observed at high concentrations. Therefore, at least three different mechanisms may contribute to the antiviral activity of ISIS 2922 in cell culture: antisense-mediated inhibition of target gene expression; nonantisense, sequence-dependent inhibition of virus replication; and sequence-independent inhibition of virus adsorption to host cells.

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Expression of the Immediate Early Gene c-fos in Basal Ganglia: Induction by Dopaminergic Drugs

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/s0317167100032480 ◽

1991 ◽

Vol 18 (S3) ◽

pp. 380-383 ◽

Cited By ~ 82

Author(s):

H.A. Robertson ◽

M.L. Paul ◽

R. Moratalla ◽

A.M. Graybiel

Keyword(s):

Dopamine Agonists ◽

Immediate Early Gene ◽

Early Gene ◽

Immediate Early ◽

Dopaminergic Drugs ◽

Protein Levels ◽

Selective Antagonists ◽

Fos Protein ◽

High Doses

ABSTRACT:Expression of the immediate early gene c-fos is increased in mammalian neurons by a number of stimuli and the usefulness of this gene as a marker of neuronal activation has been demonstrated in several systems. Directlyacting dopamine agonists of the D1-type (SKF 38393, CY 208-243) and indirectly-acting dopamine gonists (amphetamine, cocaine) all produce a rapid and transient increase in Fos protein levels in varying patterns in striatum and cerebral cortex. irectly-acting dopamine agonists only produce c-fos activation in denervated (supersensitive) striatum whereas cocaine and amphetamine activate c-fos in striatum in naive animals. Remarkably, D2 selective antagonists such as haloperidol, albeit in high doses, also activate c-fos expression. Activation of c-fos and other immediate early genes may play a part in the development of such long-term dopamine-related effects as dyskinetic movements and addiction.

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