Publications by authors named "Marco Vignuzzi"
Article Synopsis
- Chikungunya virus (CHIKV) is an emerging mosquito-borne RNA virus that can create defective viral genomes (DVGs), which help inhibit its replication and spread.
- This study examines how the RNA secondary structures of CHIKV influence the production of DVGs by using advanced techniques like SHAPE-MaP to map these structures.
- The findings show that alterations in RNA secondary structures can lead to differences in DVG generation, highlighting the role of RNA configuration in the virus's replication process.
Article Synopsis
- - Japanese encephalitis virus (JEV) is primarily spread by mosquitoes and can lead to severe illness in humans, with the potential for direct transmission observed in pigs, raising concerns about outbreaks in unvaccinated pig populations.
- - Experiments involving JEV passaging in pigs revealed increased viral replication and immune responses, but did not lead to enhanced direct transmission between pigs.
- - Genetic analysis during the experiments identified mutations that may confer advantages to the virus in pigs, highlighting the evolution of viral quasispecies without improving transmission efficiency.
Article Synopsis
- * Molecular modeling and synthesis led to the discovery of two potent α-glucosidase inhibitors, with one showing high activity against the Omicron BA.1 strain of the virus.
- * While some inhibitors showed promise, others were either ineffective or cytotoxic; however, our approach may lead to drugs that resist viral drug resistance and could be used for other viral infections.
Influenza A Virus (IAV) is a recurring respiratory virus with limited availability of antiviral therapies. Understanding host proteins essential for IAV infection can identify targets for alternative host-directed therapies (HDTs). Using affinity purification-mass spectrometry and global phosphoproteomic and protein abundance analyses using three IAV strains (pH1N1, H3N2, H5N1) in three human cell types (A549, NHBE, THP-1), we map 332 IAV-human protein-protein interactions and identify 13 IAV-modulated kinases.
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- Developing effective drugs for coronavirus infections is challenging, but recent findings highlight the sigma-1 receptor (S1R) as a promising target for antiviral treatments against SARS-CoV-1 and SARS-CoV-2.
- The S1R antagonist PB28 shows strong antiviral effects against SARS-CoV-2, and researchers developed modified versions of PB28, discovering one that is four times more effective.
- By using advanced modeling techniques, the study explores how S1R interactions with specific compounds may lead to enhanced antiviral activity, paving the way for designing new drugs targeting S1R for better virus treatment.
Article Synopsis
- The study focuses on how the Mayaro virus (MAYV) adapts to urban mosquito vectors like Ae. aegypti, which could influence its transmission and emergence as a health threat.
- Researchers discovered a specific mutation (E2-T179N) that enhances MAYV replication in mosquitoes, improving its transmission after passing through the mosquito's gut, but it reduces its ability to replicate in human cells.
- The findings suggest that while this mutation may increase the virus's ability to spread through mosquitoes, it compromises its efficiency in human hosts, indicating a complex trade-off in virus adaptation that might lead to future emergence of outbreaks.
Article Synopsis
- Viruses pose significant health challenges, leading to issues like respiratory infections, cancer, and neurological impairments, but virology research has developed vaccines and antivirals to mitigate these problems.
- The COVID-19 pandemic has heightened public scrutiny of virology, especially regarding the safe conduct of research with human pathogens, leading to confusion and misinterpretation about the origins of SARS-CoV-2.
- This article aims to clarify misconceptions by explaining gain-of-function research, the origins of SARS-CoV-2, and the regulatory frameworks in place, fostering informed discussions and emphasizing the need for balanced, evidence-based dialogue in virology.
Article Synopsis
- Viruses have historically caused serious health issues, including respiratory infections and cancer, leading to significant virology research that resulted in vaccines and antiviral treatments.
- The COVID-19 pandemic highlighted the necessity for careful research on human pathogens, creating both concerns and confusion about the safety of virology work and the origins of SARS-CoV-2.
- The article aims to clarify misunderstandings by explaining gain-of-function research, exploring the origins of SARS-CoV-2, and discussing regulatory oversight, while advocating for rational and evidence-based discussions to guide policy decisions in virology.
Article Synopsis
- Viruses pose significant health challenges, leading to various issues such as respiratory infections and cancer, prompting virology research to develop vaccines and antiviral treatments over the past 60+ years.
- The COVID-19 pandemic has intensified focus on virology, bringing up safety concerns about research involving human pathogens and creating public confusion between safe research practices and the origins of SARS-CoV-2.
- The article aims to clarify these issues by discussing gain-of-function research, the origins of SARS-CoV-2, and current regulatory frameworks, advocating for informed, balanced conversations to support necessary virology research.
Article Synopsis
- Anti-CD20 monoclonal antibodies like Rituximab are used to treat lymphomas and autoimmune diseases by depleting B cells, but some patients resist this treatment for unclear reasons.
- A CRISPR/Cas9 screen was conducted to find genes that affect the effectiveness of these antibodies, revealing MS4A1 (CD20) as expected and highlighting the role of Interferon Regulatory Factor 8 (IRF8) in the process.
- IRF8 is crucial for maintaining CD20 levels, as its absence reduces the effectiveness of antibody-induced B cell depletion, providing new insights into why some patients resist anti-CD20 therapies.
Article Synopsis
- * In French Guiana, researchers identified three mosquito populations with varying resistance levels to the insecticide deltamethrin, one showing a specific resistance allele.
- * Differences in chikungunya virus infection rates were observed among these mosquito populations, with certain genes linked to resistance being overexpressed after feeding, highlighting a potential connection that needs further investigation.
Article Synopsis
- Interferon can limit SARS-CoV-2 replication, but only a few Interferon Stimulated Genes (ISGs) with antiviral properties have been discovered.
- A CRISPR/Cas9 screening identified DAXX as a potent inhibitor of SARS-CoV-2, showing that its basic expression can restrict virus replication, especially during early infection stages.
- The study revealed that SARS-CoV-2 triggers DAXX's movement to the cytoplasm and promotes its degradation through mechanisms involving the viral protease PLpro and the proteasome, illustrating a viral strategy to evade DAXX's inhibitory effects.
Article Synopsis
- - Self-amplifying mRNA (SAM) vaccines, derived from Semliki Forest virus (SFV), have the potential to improve the efficacy and speed of vaccine development against infectious diseases and cancer.
- - Researchers optimized protocols for preparing, packaging, and measuring the titer of SFV-PD self-amplifying mRNA, specifically focusing on its expression in HEK-293 and BHK-21 cell lines.
- - The study demonstrated that BHK-21 cells yielded higher and more stable EGFP expression, and that ultrafiltration combined with RT-qPCR provided a rapid and accurate method for producing high quantities and assessing the quality of virus replicon particles for vaccine research.
Article Synopsis
- * Zebrafish larvae showed a quick decrease of SARS-CoV-2 RNA after exposure, but when the virus was introduced into the swim bladder, the viral RNA remained stable, indicating a unique reaction in this organ.
- * Despite testing multiple variants of the virus, zebrafish larvae displayed mostly low levels of infectivity, suggesting that their biology limits SARS-CoV-2 infection, particularly in areas mimicking mammalian lung functions like the swim bladder.
Article Synopsis
- - The study aimed to create a fusion protein of two specific proteins from Leishmania major and Phlebotomus papatasi, expressing it using a self-amplifying mRNA (SAM) system packaged in viral particles.
- - Two fusion combinations (PpSP15-LmSTI1 and LmSTI1-PpSP15) were analyzed for their structure and stability, revealing that PpSP15-LmSTI1 showed more favorable characteristics for mRNA folding and protein stability.
- - This research is pioneering in the use of alphavirus-derived SAM and viral replicon particles (VRPs) for targeting leishmaniasis, providing promising results for future applications in recombinant protein expression and infection of
Article Synopsis
- SARS-CoV-2 enters human cells by the Spike protein attaching to the ACE2 receptor, prompting researchers to use a targeted CRISPRi screen to explore ways to block this interaction.
- The study identifies the BRD2 protein as crucial for the transcription of ACE2 in lung and heart cells, with BRD2 inhibitors being effective at hindering ACE2 expression and preventing SARS-CoV-2 infection.
- Furthermore, the inhibition of BRD2 not only stops virus replication in Syrian hamsters but also impacts the transcription of other genes involved in the immune response, marking BRD2 as a significant target for COVID-19 therapies.
Article Synopsis
- A specific genetic variation in the APOBEC3C enzyme, affecting a single amino acid (serine to isoleucine at position 188), is found in around 10% of African populations and significantly boosts the enzyme's ability to fight off HIV-1 and SIV.
- The study observed that this variant, APOBEC3CS188I, can edit the hepatitis B virus (HBV) both in lab cultures and in infected individuals.
- Utilizing next-generation sequencing, researchers discovered that this edited variant enhances activity in a specific DNA editing context (5'TpCpA to 5'TpTpA), marking a new understanding of the enzyme's function and potential implications for HBV and nuclear DNA.
Article Synopsis
- SARS-CoV-2 infection leads to a weakened interferon response in severe COVID-19 cases, but the exact mechanisms are not fully understood.
- Researchers discovered a microRNA (miRNA) derived from a new part of the viral genome that interferes with the host's immune response by targeting key immune genes.
- The viral miRNA was found in both infected human cells and COVID-19 patient samples, suggesting that it helps the virus evade the immune system by manipulating the host's miRNA processes.
Article Synopsis
- Herpes simplex virus type 1 (HSV-1) disrupts the structure and function of mitochondria through the viral protein UL12.5, causing mitochondrial fragmentation and the release of mitochondrial DNA (mtDNA) into the cytosol.
- The presence of cytosolic mtDNA triggers immune responses, leading to an increase in type I interferon and the enzyme APOBEC3A, which is responsible for inducing mutations in mtDNA.
- The study highlights how HSV-1 infection not only damages mitochondrial networks but also utilizes released mtDNA as a danger signal to stimulate inflammation and immune reactions.
Article Synopsis
- - Rhinoviruses (RVs) cause recurrent respiratory infections and can lead to severe complications in vulnerable populations, such as those with chronic respiratory illnesses or young children prone to asthma, resulting in significant economic costs due to treatment and lost productivity.
- - This study identified specific mutations in the viral proteins VP1 and VP3 of RV-A16 that enable the virus to resist certain chemical inhibitors meant to lower endosomal pH, indicating a mechanism through which RVs adapt and survive treatment.
- - The findings suggest that using endosomal acidification inhibitors could be a promising strategy to combat RV infections, especially if these inhibitors are applied directly to the airways, despite the challenges posed by the viruses' rapid evolution and genetic diversity.
Article Synopsis
- Viral RNA-dependent RNA polymerases (RdRps) are crucial targets for broad-spectrum antiviral drugs, and a specific compound, T-1106 triphosphate, influences their function by causing delays in RNA synthesis.
- Using magnetic tweezers, researchers found that the RdRp of enterovirus A-71 utilizes a "backtracked" state to facilitate processes like copy-back RNA synthesis and homologous recombination during viral replication.
- The study indicates that pyrazine-carboxamide ribonucleotides enhance these processes without causing harmful mutations, suggesting they can promote the creation of defective viral genomes, presenting a new potential for antiviral therapies.
Article Synopsis
- SARS-CoV-2 is the virus responsible for the COVID-19 pandemic, causing over 170 million infections and 3.7 million deaths globally, making research on its biology crucial for testing, treatment, and vaccination efforts.
- The study focuses on the proteolytic cleavage of viral and cellular proteins during SARS-CoV-2 replication, using mass spectrometry to identify new cleavage sites in major viral antigens.
- Results show that certain cellular proteins are critical for the virus's replication, and targeting these with specific drugs can significantly reduce the virus in contaminated cells, aiding in the development of effective COVID-19 treatments.
Article Synopsis
- SARS-CoV-2, the virus responsible for COVID-19, has been a major public health concern since its emergence in 2019, prompting extensive data collection to inform infection control strategies.
- Mathematical modeling has been utilized to analyze the dynamics of the virus's infection, helping to predict how it spreads and suggesting effective mitigation approaches.
- In laboratory experiments, differences in viral infection rates and incubation times were found between different cell types, highlighting the importance of understanding these variations to develop targeted antiviral treatments.
A cold case: non-replicative recombination in positive-strand RNA viruses.
Virologie (Montrouge)
August 2021
Article Synopsis
- - Genetic recombination significantly influences the evolution of positive sense RNA viruses when multiple viruses infect the same cell, leading to new genetic combinations.
- - The main method of recombination involves the viral polymerase, which creates chimeric genomes by switching DNA templates during replication, though there are indications of recombination that doesn't rely on this polymerase activity.
- - It's unclear how often these non-replicative recombination events occur, how they differ from polymerase-driven recombination, or if they involve non-virus-specific sequences, suggesting a broader mechanism beyond just RNA viruses.
[A cold case: non-replicative recombination in positive-strand RNA viruses].
Virologie (Montrouge)
August 2021
Article Synopsis
- * The primary way recombination happens is through the viral polymerase switching templates during replication, but some events may occur independently of this enzyme.
- * The implications and mechanisms of non-replicative recombination are still unclear, potentially indicating a broader evolutionary role that extends beyond just viral sequences.