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23 pages, 3913 KiB

Open AccessArticle

Into the Cauldron of the Variant Soup: Insights into the Molecular Epidemiology and Transition to Endemicity of SARS-CoV-2 in Cyprus (November 2022–February 2024)

by Andreas C. Chrysostomou, The COMESSAR Network and Leondios G. Kostrikis

Viruses 2024, 16(11), 1686; https://doi.org/10.3390/v16111686 - 29 Oct 2024

Viewed by 1358

Abstract

The coronavirus disease 2019 (COVID-19) pandemic, driven by the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been characterized by the virus’s ongoing evolution, leading to the appearance of more transmissible variants that have often triggered infection surges. In this study, [...] Read more.

The coronavirus disease 2019 (COVID-19) pandemic, driven by the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been characterized by the virus’s ongoing evolution, leading to the appearance of more transmissible variants that have often triggered infection surges. In this study, we analyzed the SARS-CoV-2 epidemic in Cyprus, utilizing 1627 viral sequences from infected individuals between November 2022 and February 2024. Over this period, 251 distinct lineages and sublineages were identified, predominantly categorized into three groups: Omicron 5, XBB, and JN.1 (parental lineage BA.2.86), all of which harbor S protein mutations linked to enhanced transmissibility and immune escape. Despite the relatively low numbers of new infections during this period, and the lack of any major waves, unlike earlier phases of the pandemic, these lineages demonstrated varying periods of dominance, with Omicron 5 prevailing from November 2022 to February 2023, XBB variants leading from March to November 2023, and JN.1 generating a wavelet from December 2023 to February 2024. These findings suggest that the SARS-CoV-2 epidemic in Cyprus has reached endemicity, with new variants gradually replacing previously circulating variants irrespective of seasonal patterns. This study highlights the critical importance of ongoing surveillance of SARS-CoV-2 evolution in Cyprus and emphasizes the role of preventive measures in limiting virus transmission, providing valuable insights for safeguarding public health. Full article

(This article belongs to the Special Issue Viruses 2024—A World of Viruses)

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14 pages, 1514 KiB

Open AccessArticle

Intra-Host Citrus Tristeza Virus Populations during Prolonged Infection Initiated by a Well-Defined Sequence Variant in Nicotiana benthamiana

by Tathiana Ferreira Sa Antunes, José C. Huguet-Tapia, Santiago F. Elena and Svetlana Y. Folimonova

Viruses 2024, 16(9), 1385; https://doi.org/10.3390/v16091385 - 30 Aug 2024

Cited by 1 | Viewed by 1309

Abstract

Due to the error-prone nature of viral RNA-dependent RNA polymerases, the replication of RNA viruses results in a diversity of viral genomes harboring point mutations, deletions, insertions, and genome rearrangements. Citrus tristeza virus (CTV), a causal agent of diseases of economically important citrus [...] Read more.

Due to the error-prone nature of viral RNA-dependent RNA polymerases, the replication of RNA viruses results in a diversity of viral genomes harboring point mutations, deletions, insertions, and genome rearrangements. Citrus tristeza virus (CTV), a causal agent of diseases of economically important citrus species, shows intrinsic genetic stability. While the virus appears to have some mechanism that limits the accumulation of single-nucleotide variants, the production of defective viral genomes (DVGs) during virus infection has been reported for certain variants of CTV. The intra-host diversity generated during plant infection with variant T36 (CTV-T36) remains unclear. To address this, we analyzed the RNA species accumulated in the initially infected and systemic leaves of Nicotiana benthamiana plants inoculated with an infectious cDNA clone of CTV-T36, which warranted that infection was initiated by a known, well-defined sequence variant of the virus. CTV-T36 limited the accumulation of single-nucleotide mutants during infection. With that, four types of DVGs—deletions, insertions, and copy- and snap-backs—were found in all the samples, with deletions and insertions being the most common types. Hot-spots across the genome for DVG recombination and short direct sequence repeats suggest that sequence complementarity could mediate DVG formation. In conclusion, our study illustrates the formation of diverse DVGs during CTV-T36 infection. To the best of our knowledge, this is the first study that has analyzed the genetic variability and recombination of a well-defined sequence variant of CTV in an herbaceous host. Full article

(This article belongs to the Special Issue Viruses 2024—A World of Viruses)

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16 pages, 3588 KiB

Open AccessEditor’s ChoiceArticle

Parainfluenza Virus 5 V Protein Blocks Interferon Gamma-Mediated Upregulation of NK Cell Inhibitory Ligands and Improves NK Cell Killing of Neuroblastoma Cells

by Elisabeth M. Shiffer, Jeremiah L. Oyer, Alicja J. Copik and Griffith D. Parks

Viruses 2024, 16(8), 1270; https://doi.org/10.3390/v16081270 - 9 Aug 2024

Viewed by 1645

Abstract

Natural killer (NK) cells can be effective immunotherapeutic anti-cancer agents due to their ability to selectively target and kill tumor cells. This activity is modulated by the interaction of NK cell receptors with inhibitory ligands on the surface of target cells. NK cell [...] Read more.

Natural killer (NK) cells can be effective immunotherapeutic anti-cancer agents due to their ability to selectively target and kill tumor cells. This activity is modulated by the interaction of NK cell receptors with inhibitory ligands on the surface of target cells. NK cell inhibitory ligands can be upregulated on tumor cell surfaces in response to interferon-gamma (IFN-γ), a cytokine which is produced by activated NK cells. We hypothesized that the resistance of tumor cells to NK cell killing could be overcome by expression of the parainfluenza virus 5 (PIV5) V protein, which has known roles in blocking IFN-γ signaling. This was tested with human PM21-NK cells produced through a previously developed particle-based method which yields superior NK cells for immunotherapeutic applications. Infection of human SK-N-SH neuroblastoma cells with PIV5 blocked IFN-γ-mediated upregulation of three NK cell inhibitory ligands and enhanced in vitro killing of these tumor cells by PM21-NK cells. SK-N-SH cells transduced to constitutively express the V protein alone were resistant to IFN-γ-mediated increases in cell surface expression of NK cell inhibitory ligands. Real-time in vitro cell viability assays demonstrated that V protein expression in SK-N-SH cells was sufficient to increase PM21-NK cell-mediated killing. Toward a potential therapeutic application, transient lentiviral delivery of the V gene also enhanced PM21-NK cell killing in vitro. Our results provide the foundation for novel therapeutic applications of V protein expression in combination with ex vivo NK cell therapy to effectively increase the killing of tumor cells. Full article

(This article belongs to the Special Issue Viruses 2024—A World of Viruses)

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17 pages, 6324 KiB

Open AccessArticle

Interaction between SARS-CoV PBM and Cellular PDZ Domains Leading to Virus Virulence

by Jose M. Honrubia, Jose R. Valverde, Diego Muñoz-Santos, Jorge Ripoll-Gómez, Nuria de la Blanca, Jorge Izquierdo, Marta Villarejo-Torres, Ana Marchena-Pasero, María Rueda-Huélamo, Ivan Nombela, Mercedes Ruiz-Yuste, Sonia Zuñiga, Isabel Sola and Luis Enjuanes

Viruses 2024, 16(8), 1214; https://doi.org/10.3390/v16081214 - 29 Jul 2024

Viewed by 1264

Abstract

The interaction between SARS-CoV PDZ-binding motifs (PBMs) and cellular PDZs is responsible for virus virulence. The PBM sequence present in the 3a and envelope (E) proteins of SARS-CoV can potentially bind to over 400 cellular proteins containing PDZ domains. The role of SARS-CoV [...] Read more.

The interaction between SARS-CoV PDZ-binding motifs (PBMs) and cellular PDZs is responsible for virus virulence. The PBM sequence present in the 3a and envelope (E) proteins of SARS-CoV can potentially bind to over 400 cellular proteins containing PDZ domains. The role of SARS-CoV 3a and E proteins was studied. SARS-CoVs, in which 3a-PBM and E-PMB have been deleted (3a-PBM-/E-PBM-), reduced their titer around one logarithmic unit but still were viable. In addition, the absence of the E-PBM and the replacement of 3a-PBM with that of E did not allow the rescue of SARS-CoV. E protein PBM was necessary for virulence, activating p38-MAPK through the interaction with Syntenin-1 PDZ domain. However, the presence or absence of the homologous motif in the 3a protein, which does not bind to Syntenin-1, did not affect virus pathogenicity. Mutagenesis analysis and in silico modeling were performed to study the extension of the PBM of the SARS-CoV E protein. Alanine and glycine scanning was performed revealing a pair of amino acids necessary for optimum virus replication. The binding of E protein with the PDZ2 domain of the Syntenin-1 homodimer induced conformational changes in both PDZ domains 1 and 2 of the dimer. Full article

(This article belongs to the Special Issue Viruses 2024—A World of Viruses)

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28 pages, 7343 KiB

Open AccessArticle

Accumulation Dynamics of Defective Genomes during Experimental Evolution of Two Betacoronaviruses

by Julia Hillung, María J. Olmo-Uceda, Juan C. Muñoz-Sánchez and Santiago F. Elena

Viruses 2024, 16(4), 644; https://doi.org/10.3390/v16040644 - 20 Apr 2024

Cited by 7 | Viewed by 2007

Abstract

Virus-encoded replicases often generate aberrant RNA genomes, known as defective viral genomes (DVGs). When co-infected with a helper virus providing necessary proteins, DVGs can multiply and spread. While DVGs depend on the helper virus for propagation, they can in some cases disrupt infectious [...] Read more.

Virus-encoded replicases often generate aberrant RNA genomes, known as defective viral genomes (DVGs). When co-infected with a helper virus providing necessary proteins, DVGs can multiply and spread. While DVGs depend on the helper virus for propagation, they can in some cases disrupt infectious virus replication, impact immune responses, and affect viral persistence or evolution. Understanding the dynamics of DVGs alongside standard viral genomes during infection remains unclear. To address this, we conducted a long-term experimental evolution of two betacoronaviruses, the human coronavirus OC43 (HCoV-OC43) and the murine hepatitis virus (MHV), in cell culture at both high and low multiplicities of infection (MOI). We then performed RNA-seq at regular time intervals, reconstructed DVGs, and analyzed their accumulation dynamics. Our findings indicate that DVGs evolved to exhibit greater diversity and abundance, with deletions and insertions being the most common types. Notably, some high MOI deletions showed very limited temporary existence, while others became prevalent over time. We observed differences in DVG abundance between high and low MOI conditions in HCoV-OC43 samples. The size distribution of HCoV-OC43 genomes with deletions differed between high and low MOI passages. In low MOI lineages, short and long DVGs were the most common, with an additional cluster in high MOI lineages which became more prevalent along evolutionary time. MHV also showed variations in DVG size distribution at different MOI conditions, though they were less pronounced compared to HCoV-OC43, suggesting a more random distribution of DVG sizes. We identified hotspot regions for deletions that evolved at a high MOI, primarily within cistrons encoding structural and accessory proteins. In conclusion, our study illustrates the widespread formation of DVGs during betacoronavirus evolution, influenced by MOI and cell- and virus-specific factors. Full article

(This article belongs to the Special Issue Viruses 2024—A World of Viruses)

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12 pages, 3122 KiB

Open AccessArticle

Effects of Strain Differences, Humidity Changes, and Saliva Contamination on the Inactivation of SARS-CoV-2 by Ion Irradiation

by Afifah Fatimah Azzahra Ahmad Wadi, Daichi Onomura, Hirokazu Funamori, Mst Mahmuda Khatun, Shunpei Okada, Hisashi Iizasa and Hironori Yoshiyama

Viruses 2024, 16(4), 520; https://doi.org/10.3390/v16040520 - 28 Mar 2024

Cited by 1 | Viewed by 1531

Abstract

One of the methods to inactivate viruses is to denature viral proteins using released ions. However, there have been no reports detailing the effects of changes in humidity or contamination with body fluids on the inactivation of viruses. This study investigated the effects [...] Read more.

One of the methods to inactivate viruses is to denature viral proteins using released ions. However, there have been no reports detailing the effects of changes in humidity or contamination with body fluids on the inactivation of viruses. This study investigated the effects of humidity changes and saliva contamination on the efficacy of SARS-CoV-2 inactivation with ions using multiple viral strains. Virus solutions with different infectious titers were dropped onto a circular nitrocellulose membrane and irradiated with ions from 10 cm above the membrane. After the irradiation of ions for 60, 90, and 120 min, changes in viral infectious titers were measured. The effect of ions on virus inactivation under different humidity conditions was also examined using virus solutions containing 90% mixtures of saliva collected from 10 people. A decrease in viral infectivity was observed over time for all strains, but ion irradiation further accelerated the decrease in viral infectivity. Ion irradiation can inactivate all viral strains, but at 80% humidity, the effect did not appear until 90 min after irradiation. The presence of saliva protected the virus from drying and maintained infectiousness for a longer period compared with no saliva. In particular, the Omicron strain retained its infectivity titer longer than the other strains. Ion irradiation demonstrated a consistent reduction in the number of infectious viruses when compared to the control across varying levels of humidity and irradiation periods. This underscores the notable effectiveness of irradiation, even when the reduction effect is as modest as 50%, thereby emphasizing its crucial role in mitigating the rapid dissemination of SARS-CoV-2. Full article

(This article belongs to the Special Issue Viruses 2024—A World of Viruses)

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Review

Jump to: Research

15 pages, 1588 KiB

Open AccessReview

No Time to Die: How Cytomegaloviruses Suppress Apoptosis, Necroptosis, and Pyroptosis

by Yingqi Deng, Ana Águeda-Pinto and Wolfram Brune

Viruses 2024, 16(8), 1272; https://doi.org/10.3390/v16081272 - 9 Aug 2024

Cited by 3 | Viewed by 1756

Abstract

Viruses are obligate intracellular pathogens as their replication depends on the metabolism of the host cell. The induction of cellular suicide, known as programmed cell death (PCD), has the potential to hinder viral replication and act as a first line of defense against [...] Read more.

Viruses are obligate intracellular pathogens as their replication depends on the metabolism of the host cell. The induction of cellular suicide, known as programmed cell death (PCD), has the potential to hinder viral replication and act as a first line of defense against viral pathogens. Apoptosis, necroptosis, and pyroptosis are three important PCD modalities. Different signaling pathways are involved in their execution, and they also differ in their ability to cause inflammation. Cytomegaloviruses (CMV), beta-herpesviruses with large double-stranded DNA genomes, encode a great variety of immune evasion genes, including several cell death suppressors. While CMV inhibitors of apoptosis and necroptosis have been known and studied for years, the first pyroptosis inhibitor has been identified and characterized only recently. Here, we describe how human and murine CMV interfere with apoptosis, necroptosis, and pyroptosis signaling pathways. We also discuss the importance of the different PCD forms and their viral inhibitors for the containment of viral replication and spread in vivo. Full article

(This article belongs to the Special Issue Viruses 2024—A World of Viruses)

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28 pages, 487 KiB

Open AccessReview

Pseudomonas aeruginosa Bacteriophages and Their Clinical Applications

by Elaheh Alipour-Khezri, Mikael Skurnik and Gholamreza Zarrini

Viruses 2024, 16(7), 1051; https://doi.org/10.3390/v16071051 - 29 Jun 2024

Cited by 9 | Viewed by 5201

Abstract

Antimicrobial resistance poses a serious risk to contemporary healthcare since it reduces the number of bacterial illnesses that may be treated with antibiotics, particularly for patients with long-term conditions like cystic fibrosis (CF). People with a genetic predisposition to CF often have recurrent [...] Read more.

Antimicrobial resistance poses a serious risk to contemporary healthcare since it reduces the number of bacterial illnesses that may be treated with antibiotics, particularly for patients with long-term conditions like cystic fibrosis (CF). People with a genetic predisposition to CF often have recurrent bacterial infections in their lungs due to a buildup of sticky mucus, necessitating long-term antibiotic treatment. Pseudomonas aeruginosa infections are a major cause of CF lung illness, and P. aeruginosa airway isolates are frequently resistant to many antibiotics. Bacteriophages (also known as phages), viruses that infect bacteria, are a viable substitute for antimicrobials to treat P. aeruginosa infections in individuals with CF. Here, we reviewed the utilization of P. aeruginosa bacteriophages both in vivo and in vitro, as well as in the treatment of illnesses and diseases, and the outcomes of the latter. Full article

(This article belongs to the Special Issue Viruses 2024—A World of Viruses)

7 pages, 271 KiB

Open AccessReview

Significance of Cellular Lipid Metabolism for the Replication of Rotaviruses and Other RNA Viruses

by Ulrich Desselberger

Viruses 2024, 16(6), 908; https://doi.org/10.3390/v16060908 - 4 Jun 2024

Cited by 1 | Viewed by 1349

Abstract

The replication of species A rotaviruses (RVAs) involves the recruitment of and interaction with cellular organelles’ lipid droplets (LDs), both physically and functionally. The inhibition of enzymes involved in the cellular fatty acid biosynthesis pathway or the inhibition of cellular lipases that degrade [...] Read more.

The replication of species A rotaviruses (RVAs) involves the recruitment of and interaction with cellular organelles’ lipid droplets (LDs), both physically and functionally. The inhibition of enzymes involved in the cellular fatty acid biosynthesis pathway or the inhibition of cellular lipases that degrade LDs was found to reduce the functions of ‘viral factories’ (viroplasms for rotaviruses or replication compartments of other RNA viruses) and decrease the production of infectious progeny viruses. While many other RNA viruses utilize cellular lipids for their replication, their detailed analysis is far beyond this review; only a few annotations are made relating to hepatitis C virus (HCV), enteroviruses, SARS-CoV-2, and HIV-1. Full article

(This article belongs to the Special Issue Viruses 2024—A World of Viruses)

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