Viruses

Editorial

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4 pages, 2235 KiB

Open AccessEditorial

The Era of the FLips: How Spike Mutations L455F and F456L (and A475V) Are Shaping SARS-CoV-2 Evolution

by Daniele Focosi, Pietro Giorgio Spezia, Federico Gueli and Fabrizio Maggi

Viruses 2024, 16(1), 3; https://doi.org/10.3390/v16010003 - 19 Dec 2023

Cited by 11 | Viewed by 2234

Abstract

Convergent evolution of the SARS-CoV-2 Spike protein has been mostly driven by immune escape, in particular by escape to the viral infection-neutralizing antibodies (nAbs) elicited by previous infections and/or vaccinations [...] Full article

(This article belongs to the Special Issue Emerging Concepts in SARS-CoV-2 Biology and Pathology 2.0)

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Research

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22 pages, 13849 KiB

Open AccessArticle

Kinetic Landscape of Single Virus-like Particles Highlights the Efficacy of SARS-CoV-2 Internalization

by Aleksandar Atemin, Aneliya Ivanova, Wiley Peppel, Rumen Stamatov, Rodrigo Gallegos, Haley Durden, Sonya Uzunova, Michael D. Vershinin, Saveez Saffarian and Stoyno S. Stoynov

Viruses 2024, 16(8), 1341; https://doi.org/10.3390/v16081341 - 22 Aug 2024

Viewed by 3722

Abstract

The efficiency of virus internalization into target cells is a major determinant of infectivity. SARS-CoV-2 internalization occurs via S-protein-mediated cell binding followed either by direct fusion with the plasma membrane or endocytosis and subsequent fusion with the endosomal membrane. Despite the crucial role [...] Read more.

The efficiency of virus internalization into target cells is a major determinant of infectivity. SARS-CoV-2 internalization occurs via S-protein-mediated cell binding followed either by direct fusion with the plasma membrane or endocytosis and subsequent fusion with the endosomal membrane. Despite the crucial role of virus internalization, the precise kinetics of the processes involved remains elusive. We developed a pipeline, which combines live-cell microscopy and advanced image analysis, for measuring the rates of multiple internalization-associated molecular events of single SARS-CoV-2-virus-like particles (VLPs), including endosome ingression and pH change. Our live-cell imaging experiments demonstrate that only a few minutes after binding to the plasma membrane, VLPs ingress into RAP5-negative endosomes via dynamin-dependent scission. Less than two minutes later, VLP speed increases in parallel with a pH drop below 5, yet these two events are not interrelated. By co-imaging fluorescently labeled nucleocapsid proteins, we show that nucleocapsid release occurs with similar kinetics to VLP acidification. Neither Omicron mutations nor abrogation of the S protein polybasic cleavage site affected the rate of VLP internalization, indicating that they do not confer any significant advantages or disadvantages during this process. Finally, we observe that VLP internalization occurs two to three times faster in VeroE6 than in A549 cells, which may contribute to the greater susceptibility of the former cell line to SARS-CoV-2 infection. Taken together, our precise measurements of the kinetics of VLP internalization-associated processes shed light on their contribution to the effectiveness of SARS-CoV-2 propagation in cells. Full article

(This article belongs to the Special Issue Emerging Concepts in SARS-CoV-2 Biology and Pathology 2.0)

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15 pages, 2649 KiB

Open AccessArticle

Emergence of Recombinant SARS-CoV-2 Variants in California from 2020 to 2022

by Rahil Ryder, Emily Smith, Deva Borthwick, Jesse Elder, Mayuri Panditrao, Christina Morales and Debra A. Wadford

Viruses 2024, 16(8), 1209; https://doi.org/10.3390/v16081209 - 27 Jul 2024

Viewed by 942

Abstract

The detection, characterization, and monitoring of SARS-CoV-2 recombinant variants constitute a challenge for public health authorities worldwide. Recombinant variants, composed of two or more SARS-CoV-2 lineages, often have unknown impacts on transmission, immune escape, and virulence in the early stages of emergence. We [...] Read more.

The detection, characterization, and monitoring of SARS-CoV-2 recombinant variants constitute a challenge for public health authorities worldwide. Recombinant variants, composed of two or more SARS-CoV-2 lineages, often have unknown impacts on transmission, immune escape, and virulence in the early stages of emergence. We examined 4213 SARS-CoV-2 recombinant SARS-CoV-2 genomes collected between 2020 and 2022 in California to describe regional and statewide trends in prevalence. Many of these recombinant genomes, such as those belonging to the XZ lineage or novel recombinant lineages, likely originated within the state of California. We discuss the challenges and limitations surrounding Pango lineage assignments, the use of publicly available sequence data, and adequate sample sizes for epidemiologic analyses. Although these challenges will continue as SARS-CoV-2 sequencing volumes decrease globally, this study enhances our understanding of SARS-CoV-2 recombinant genomes to date while providing a foundation for future insights into emerging recombinant lineages. Full article

(This article belongs to the Special Issue Emerging Concepts in SARS-CoV-2 Biology and Pathology 2.0)

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16 pages, 2140 KiB

Open AccessArticle

Gene Regulatory Network Analysis of Post-Mortem Lungs Unveils Novel Insights into COVID-19 Pathogenesis

by Ryan Bloomquist, Ashis K. Mondal, Ashutosh Vashisht, Nikhil Sahajpal, Kimya Jones, Vishakha Vashisht, Harmanpreet Singh, Jaspreet Farmaha and Ravindra Kolhe

Viruses 2024, 16(6), 853; https://doi.org/10.3390/v16060853 - 27 May 2024

Viewed by 1168

Abstract

The novel coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has emerged as one of the most significant global health crises in recent history. The clinical characteristics of COVID-19 patients have revealed the possibility of immune activity [...] Read more.

The novel coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has emerged as one of the most significant global health crises in recent history. The clinical characteristics of COVID-19 patients have revealed the possibility of immune activity changes contributing to disease severity. Nevertheless, limited information is available regarding the immune response in human lung tissue, which is the primary site of infection. In this study, we conducted an extensive analysis of lung tissue to screen for differentially expressed miRNAs and mRNAs in five individuals who died due to COVID-19 and underwent a rapid autopsy, as well as seven control individuals who died of other causes unrelated to COVID-19. To analyze the host response gene expression, miRNA microarray and Nanostring’s nCounter XT gene expression assay were performed. Our study identified 37 downregulated and 77 upregulated miRNAs in COVID-19 lung biopsy samples compared to the controls. A total of 653 mRNA transcripts were differentially expressed between the two sample types, with most transcripts (472) being downregulated in COVID-19-positive specimens. Hierarchical and PCA K-means clustering analysis showed distinct clustering between COVID-19 and control samples. Enrichment and network analyses revealed differentially expressed genes important for innate immunity and inflammatory response in COVID-19 lung biopsies. The interferon-signaling pathway was highly upregulated in COVID-19 specimens while genes involved in interleukin-17 signaling were downregulated. These findings shed light on the mechanisms of host cellular responses to COVID-19 infection in lung tissues and could help identify new targets for the prevention and treatment of COVID-19 infection. Full article

(This article belongs to the Special Issue Emerging Concepts in SARS-CoV-2 Biology and Pathology 2.0)

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15 pages, 2520 KiB

Open AccessArticle

Natural Killer Cells Do Not Attenuate a Mouse-Adapted SARS-CoV-2-Induced Disease in Rag2^−/− Mice

by Calder R Ellsworth, Chenxiao Wang, Alexis R Katz, Zheng Chen, Mohammad Islamuddin, Haoran Yang, Sarah E Scheuermann, Kelly A Goff, Nicholas J Maness, Robert V Blair, Jay K Kolls and Xuebin Qin

Viruses 2024, 16(4), 611; https://doi.org/10.3390/v16040611 - 15 Apr 2024

Cited by 2 | Viewed by 1544

Abstract

This study investigates the roles of T, B, and Natural Killer (NK) cells in the pathogenesis of severe COVID-19, utilizing mouse-adapted SARS-CoV-2-MA30 (MA30). To evaluate this MA30 mouse model, we characterized MA30-infected C57BL/6 mice (B6) and compared them with SARS-CoV-2-WA1 (an original SARS-CoV-2 [...] Read more.

This study investigates the roles of T, B, and Natural Killer (NK) cells in the pathogenesis of severe COVID-19, utilizing mouse-adapted SARS-CoV-2-MA30 (MA30). To evaluate this MA30 mouse model, we characterized MA30-infected C57BL/6 mice (B6) and compared them with SARS-CoV-2-WA1 (an original SARS-CoV-2 strain) infected K18-human ACE2 (K18-hACE2) mice. We found that the infected B6 mice developed severe peribronchial inflammation and rapid severe pulmonary edema, but less lung interstitial inflammation than the infected K18-hACE2 mice. These pathological findings recapitulate some pathological changes seen in severe COVID-19 patients. Using this MA30-infected mouse model, we further demonstrate that T and/or B cells are essential in mounting an effective immune response against SARS-CoV-2. This was evident as Rag2^−/− showed heightened vulnerability to infection and inhibited viral clearance. Conversely, the depletion of NK cells did not significantly alter the disease course in Rag2^−/− mice, underscoring the minimal role of NK cells in the acute phase of MA30-induced disease. Together, our results indicate that T and/or B cells, but not NK cells, mitigate MA30-induced disease in mice and the infected mouse model can be used for dissecting the pathogenesis and immunology of severe COVID-19. Full article

(This article belongs to the Special Issue Emerging Concepts in SARS-CoV-2 Biology and Pathology 2.0)

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14 pages, 2204 KiB

Open AccessArticle

Establishment of the First National Standard for Neutralizing Antibodies against SARS-CoV-2 XBB Variants

by Xuanxuan Zhang, Lidong Guan, Na Li, Ying Wang, Lu Li, Mingchen Liu, Qian He, Jiansheng Lu, Haiyuan Zeng, Shan Yu, Xinyi Guo, Jiali Gong, Jing Li, Fan Gao, Xing Wu, Si Chen, Qian Wang, Zhongfang Wang, Weijin Huang, Qunying Mao, Zhenglun Liang and Miao Xu Show full author list Hide full author list

Viruses 2024, 16(4), 554; https://doi.org/10.3390/v16040554 - 1 Apr 2024

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Abstract

Neutralizing antibodies (NtAbs) against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) are indicators of vaccine efficacy that enable immunity surveillance. However, the rapid mutation of SARS-CoV-2 variants prevents the timely establishment of standards required for effective XBB vaccine evaluation. Therefore, we prepared four candidate [...] Read more.

Neutralizing antibodies (NtAbs) against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) are indicators of vaccine efficacy that enable immunity surveillance. However, the rapid mutation of SARS-CoV-2 variants prevents the timely establishment of standards required for effective XBB vaccine evaluation. Therefore, we prepared four candidate standards (No. 11, No. 44, No. 22, and No. 33) using plasma, purified immunoglobulin, and a broad-spectrum neutralizing monoclonal antibody. Collaborative calibration was conducted across nine Chinese laboratories using neutralization methods against 11 strains containing the XBB and BA.2.86 sublineages. This study demonstrated the reduced neutralization potency of the first International Standard antibodies to SARS-CoV-2 variants of concern against XBB variants. No. 44 displayed broad-spectrum neutralizing activity against XBB sublineages, effectively reduced interlaboratory variability for nearly all XBB variants, and effectively minimized the geometric mean titer (GMT) difference between the live and pseudotyped virus. No. 22 showed a broader spectrum and higher neutralizing activity against all strains but failed to reduce interlaboratory variability. Thus, No. 44 was approved as a National Standard for NtAbs against XBB variants, providing a unified NtAb measurement standard for XBB variants for the first time. Moreover, No. 22 was approved as a national reference reagent for NtAbs against SARS-CoV-2, offering a broad-spectrum activity reference for current and potentially emerging variants. Full article

(This article belongs to the Special Issue Emerging Concepts in SARS-CoV-2 Biology and Pathology 2.0)

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Review

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20 pages, 1833 KiB

Open AccessReview

Is Autophagy a Friend or Foe in SARS-CoV-2 Infection?

by Asifa Khan, Jiaxin Ling and Jinlin Li

Viruses 2024, 16(9), 1491; https://doi.org/10.3390/v16091491 - 20 Sep 2024

Viewed by 1038

Abstract

As obligate parasites, viruses need to hijack resources from infected cells to complete their lifecycle. The interaction between the virus and host determines the viral infection process, including viral propagation and the disease’s outcome. Understanding the interaction between the virus and host factors [...] Read more.

As obligate parasites, viruses need to hijack resources from infected cells to complete their lifecycle. The interaction between the virus and host determines the viral infection process, including viral propagation and the disease’s outcome. Understanding the interaction between the virus and host factors is a basis for unraveling the intricate biological processes in the infected cells and thereby developing more efficient and targeted antivirals. Among the various fundamental virus–host interactions, autophagy plays vital and also complicated roles by directly engaging in the viral lifecycle and functioning as an anti- and/or pro-viral factor. Autophagy thus becomes a promising target against virus infection. Since the COVID-19 pandemic, there has been an accumulation of studies aiming to investigate the roles of autophagy in SARS-CoV-2 infection by using different models and from distinct angles, providing valuable information for systematically and comprehensively dissecting the interplay between autophagy and SARS-CoV-2. In this review, we summarize the advancements in the studies of the interaction between SARS-CoV-2 and autophagy, as well as detailed molecular mechanisms. We also update the current knowledge on the pharmacological strategies used to suppress SARS-CoV-2 replication through remodeling autophagy. These extensive studies on SARS-CoV-2 and autophagy can advance our understanding of virus–autophagy interaction and provide insights into developing efficient antiviral therapeutics by regulating autophagy. Full article

(This article belongs to the Special Issue Emerging Concepts in SARS-CoV-2 Biology and Pathology 2.0)

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15 pages, 762 KiB

Open AccessReview

SARS-CoV-2 Variants and COVID-19 in Bangladesh—Lessons Learned

by Simon D. Lytton and Asish Kumar Ghosh

Viruses 2024, 16(7), 1077; https://doi.org/10.3390/v16071077 - 4 Jul 2024

Viewed by 1029

Abstract

The coronavirus infectious disease-2019 (COVID-19) in Bangladesh is a paradigm for how one of the most densely populated countries in the world, with 1270 people per square kilometer, managed to cope with the COVID-19 pandemic under extraordinary circumstances. This review highlights the SARS-CoV-2 [...] Read more.

The coronavirus infectious disease-2019 (COVID-19) in Bangladesh is a paradigm for how one of the most densely populated countries in the world, with 1270 people per square kilometer, managed to cope with the COVID-19 pandemic under extraordinary circumstances. This review highlights the SARS-CoV-2 variants in Bangladesh and the timeline of their detection in the context of the global experience with the management of vaccination and natural SARS-CoV-2 infection. The motivation to overcome the COVID-19 vaccine dilemma and track Bangladeshi SARS-CoV-2 sub-variants underscores the potential for a low-income country to excel in international medical science, despite having stressed health care services and limited availability of resources for SARS-CoV-2 testing and gene sequencing. Full article

(This article belongs to the Special Issue Emerging Concepts in SARS-CoV-2 Biology and Pathology 2.0)

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15 pages, 2428 KiB

Open AccessReview

SARS-CoV-2 ORF8 as a Modulator of Cytokine Induction: Evidence and Search for Molecular Mechanisms

by Marília Inês Móvio, Giovana Waner Carneiro de Almeida, Isabella das Graças Lopes Martines, Gilmara Barros de Lima, Sergio Daishi Sasaki, Alexandre Hiroaki Kihara, Emma Poole, Michael Nevels and Maria Cristina Carlan da Silva

Viruses 2024, 16(1), 161; https://doi.org/10.3390/v16010161 - 22 Jan 2024

Cited by 2 | Viewed by 2170

Abstract

Severe cases of SARS-CoV-2 infection are characterized by an immune response that leads to the overproduction of pro-inflammatory cytokines, resulting in lung damage, cardiovascular symptoms, hematologic symptoms, acute kidney injury and multiple organ failure that can lead to death. This remarkable increase in [...] Read more.

Severe cases of SARS-CoV-2 infection are characterized by an immune response that leads to the overproduction of pro-inflammatory cytokines, resulting in lung damage, cardiovascular symptoms, hematologic symptoms, acute kidney injury and multiple organ failure that can lead to death. This remarkable increase in cytokines and other inflammatory molecules is primarily caused by viral proteins, and particular interest has been given to ORF8, a unique accessory protein specific to SARS-CoV-2. Despite plenty of research, the precise mechanisms by which ORF8 induces proinflammatory cytokines are not clear. Our investigations demonstrated that ORF8 augments production of IL-6 induced by Poly(I:C) in human embryonic kidney (HEK)-293 and monocyte-derived dendritic cells (mono-DCs). We discuss our findings and the multifaceted roles of ORF8 as a modulator of cytokine response, focusing on type I interferon and IL-6, a key component of the immune response to SARS-CoV-2. In addition, we explore the hypothesis that ORF8 may act through pattern recognition receptors of dsRNA such as TLRs. Full article

(This article belongs to the Special Issue Emerging Concepts in SARS-CoV-2 Biology and Pathology 2.0)

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