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Viruses
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State-of-the-Art Virology Research in Croatia 2022
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State-of-the-Art Virology Research in Croatia 2022

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "General Virology".

Deadline for manuscript submissions: closed (31 December 2022) | Viewed by 12848

Special Issue Editors

Prof. Dr. Stipan Jonjić

E-Mail Website1 Website2
Guest Editor
1. Center of Excellence for Viral Immunology and Vaccines, CERVirVac, 10000 Zagreb, Croatia
2. Croatia Center for Proteomics, Faculty of Medicine, University of Rijeka, 51000 Rijeka, Croatia
Interests: MCMV; immunobiology of perinatal CMV infection of CNS; transcriptomic approach to viral disease; viral evasion
Special Issues, Collections and Topics in MDPI journals
Dr. Dubravko Forčić

E-Mail Website
Guest Editor
1. Center for Research and Knowledge Transfer in Biotechnology, University of Zagreb, Zagreb, Croatia
2. Center of Excellence for Viral Immunology and Vaccines, CERVirVac, 10000 Zagreb, Croatia
Interests: paramyxoviruses; molecular epidemiology; genetic variability; mumps virus
Special Issues, Collections and Topics in MDPI journals
Dr. Andreja Ambriović-Ristov

E-Mail Website
Guest Editor
Laboratory for Cell Biology and Signalling, Division of Molecular Biology, Ruđer Bošković Institute, Bijenička 54, 10000 Zagreb, Croatia
Interests: adenoviral vectors; adenovirus retargeting; integrin; adhesion; adhesome; cell migration; integrin-mediated cancer cell chemoresistance

Special Issue Information

Dear Colleagues,

Croatian scientists actively participate in fundamental studies of different viral pathogens, such as herpesviruses, adenoviruses, papillomaviruses, arboviruses, flaviviruses, rotaviruses, hantaviruses, and several others, with a focus on virology, viral immunology, pathogenesis, viral genetic diversity, and evolution. Furthermore, Croatian scientists’ research efforts also include developing novel viral and vaccine vectors, intensive investigations on papillomavirus-induced oncogenesis, and the molecular epidemiology of several human viral pathogens as well as investigations on viral zoonoses and the diversity of plant viruses and subviral pathogens and their impact on the ecosystems. In addition, Croatia is home to a scientific center of excellent repute dedicated to the study of virology: the Center of Excellence for Viral Immunology and Vaccines. The center hosts several research groups from the University of Rijeka and at the University of Zagreb and aims to become a vital facility for the further development of viral immunology and vaccinology in Croatia. The Center for Excellence's principal activities include studies on the basic mechanisms of virus control, viral evasion of the immune response, and the design of effective novel viral vaccines and vaccine vectors. Furthermore, following the emergence of the COVID-19 pandemic, significant activity in coronavirus research, supported mainly through the Croatian Science Foundation, has arisen in Croatia as well. The second edition of this Special Issue will provide an overview of research on virology and viral pathogenesis within the country. We are inviting colleagues to contribute reviews or original articles related to their research to this issue.

Prof. Dr. Stipan Jonjić
Dr. Dubravko Forčić
Dr. Andreja Ambriović-Ristov
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Viruses is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • human, animal and plant viruses
  • viral evolution and genetics
  • viral entry, assembly and release
  • viral pathogenesis
  • viral vectors
  • virus and host cell interaction
  • immune response to viruses and viral immunoevasion
  • viral diagnostics, therapy and interventions

Published Papers (5 papers)

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Research

28 pages, 4950 KiB  
Article
Membraneless Compartmentalization of Nuclear Assembly Sites during Murine Cytomegalovirus Infection
by Hana Mahmutefendić Lučin, Silvija Lukanović Jurić, Marina Marcelić, Igor Štimac, Ivona Viduka, Gordana Blagojević Zagorac, Berislav Lisnić, Zsolt Ruzsics and Pero Lučin
Viruses 2023, 15(3), 766; https://doi.org/10.3390/v15030766 - 16 Mar 2023
Viewed by 1582
Abstract
Extensive reorganization of infected cells and the formation of large structures known as the nuclear replication compartment (RC) and cytoplasmic assembly compartment (AC) is a hallmark of beta-herpesvirus infection. These restructurings rely on extensive compartmentalization of the processes that make up the virus [...] Read more.
Extensive reorganization of infected cells and the formation of large structures known as the nuclear replication compartment (RC) and cytoplasmic assembly compartment (AC) is a hallmark of beta-herpesvirus infection. These restructurings rely on extensive compartmentalization of the processes that make up the virus manufacturing chain. Compartmentalization of the nuclear processes during murine cytomegalovirus (MCMV) infection is not well described. In this study, we visualized five viral proteins (pIE1, pE1, pM25, pm48.2, and pM57) and replicated viral DNA to reveal the nuclear events during MCMV infection. As expected, these events can be matched with those described for other beta and alpha herpesviruses and contribute to the overall picture of herpesvirus assembly. Imaging showed that four viral proteins (pE1, pM25, pm48.2, and pM57) and replicated viral DNA condense in the nucleus into membraneless assemblies (MLAs) that undergo a maturation sequence to form the RC. One of these proteins (pM25), which is also expressed in a cytoplasmic form (pM25l), showed similar MLAs in the AC. Bioinformatics tools for predicting biomolecular condensates showed that four of the five proteins had a high propensity for liquid–liquid phase separation (LLPS), suggesting that LLPS may be a mechanism for compartmentalization within RC and AC. Examination of the physical properties of MLAs formed during the early phase of infection by 1,6-hexanediol treatment in vivo revealed liquid-like properties of pE1 MLAs and more solid-like properties of pM25 MLAs, indicating heterogeneity of mechanisms in the formation of virus-induced MLAs. Analysis of the five viral proteins and replicated viral DNA shows that the maturation sequence of RC and AC is not completed in many cells, suggesting that virus production and release is carried out by a rather limited number of cells. This study thus lays the groundwork for further investigation of the replication cycle of beta-herpesviruses, and the results should be incorporated into plans for high-throughput and single-cell analytic approaches. Full article
(This article belongs to the Special Issue State-of-the-Art Virology Research in Croatia 2022)
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22 pages, 2123 KiB  
Article
SARS-CoV-2 Spike and Nucleocapsid Antibody Response in Vaccinated Croatian Healthcare Workers and Infected Hospitalized Patients: A Single Center Cohort Study
by Paola Kučan Brlić, Martina Pavletić, Mate Lerga, Fran Krstanović, Marina Pribanić Matešić, Karmela Miklić, Suzana Malić, Leonarda Mikša, Maja Pajcur, Dolores Peruč, Maren Schubert, Federico Bertoglio, Jurica Arapović, Alen Protić, Alan Šustić, Marko Milošević, Luka Čičin Šain, Stipan Jonjić, Vanda Juranić Lisnić and Ilija Brizić
Viruses 2022, 14(9), 1966; https://doi.org/10.3390/v14091966 - 4 Sep 2022
Cited by 6 | Viewed by 2378
Abstract
Studies assessing the dynamics and duration of antibody responses following SARS-CoV-2 infection or vaccination are an invaluable tool for vaccination schedule planning, assessment of risk groups and management of pandemics. In this study, we developed and employed ELISA assays to analyze the humoral [...] Read more.
Studies assessing the dynamics and duration of antibody responses following SARS-CoV-2 infection or vaccination are an invaluable tool for vaccination schedule planning, assessment of risk groups and management of pandemics. In this study, we developed and employed ELISA assays to analyze the humoral responses to Nucleocapsid and Spike proteins in vaccinated health-care workers (HCW) and critically ill COVID-19 patients. Sera of more than 1000 HCWs and critically ill patients from the Clinical Hospital Center Rijeka were tested across a one-year period, encompassing the spread of major SARS-CoV-2 variants of concern (VOCs). We observed 97% of seroconversion in HCW cohort as well as sustained anti-Spike antibody response in vaccinees for more than 6 months. In contrast, the infection-induced anti-Nucleocapsid response was waning significantly in a six-month period. Furthermore, a substantial decrease in vaccinees’ anti-Spike antibodies binding to Spike protein of Omicron VOC was also observed. Critically ill COVID-19 patients had higher levels of anti-Spike and anti-Nucleocapsid antibodies compared to HCWs. No significant differences in anti-Spike and anti-Nucleocapsid antibody levels between the critically ill COVID-19 patients that were on non-invasive oxygen supplementation and those on invasive ventilation support were observed. However, stronger anti-Spike, but not anti-Nucleocapsid, antibody response correlated with a better disease outcome in the cohort of patients on invasive ventilation support. Altogether, our results contribute to the growing pool of data on humoral responses to SARS-CoV-2 infection and vaccination. Full article
(This article belongs to the Special Issue State-of-the-Art Virology Research in Croatia 2022)
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15 pages, 4397 KiB  
Article
SARS-CoV-2 Viral Load in the Pulmonary Compartment of Critically Ill COVID-19 Patients Correlates with Viral Serum Load and Fatal Outcomes
by Mario Ynga-Durand, Henrike Maaß, Marko Milošević, Fran Krstanović, Marina Pribanić Matešić, Stipan Jonjić, Alen Protić, Ilija Brizić, Alan Šustić and Luka Čičin-Šain
Viruses 2022, 14(6), 1292; https://doi.org/10.3390/v14061292 - 14 Jun 2022
Cited by 7 | Viewed by 3283
Abstract
While SARS-CoV-2 detection in sputum and swabs from the upper respiratory tract has been used as a diagnostic tool, virus quantification showed poor correlation to disease outcome and thus, poor prognostic value. Although the pulmonary compartment represents a relevant site for viral load [...] Read more.
While SARS-CoV-2 detection in sputum and swabs from the upper respiratory tract has been used as a diagnostic tool, virus quantification showed poor correlation to disease outcome and thus, poor prognostic value. Although the pulmonary compartment represents a relevant site for viral load analysis, limited data exploring the lower respiratory tract is available, and its association to clinical outcomes is relatively unknown. Using bronchoalveolar lavage (BAL) and serum samples, we quantified SARS-CoV-2 copy numbers in the pulmonary and systemic compartments of critically ill patients admitted to the intensive care unit of a COVID-19 referral hospital in Croatia during the second and third pandemic waves. Clinical data, including 30-day survival after ICU admission, were included. We found that elevated SARS-CoV-2 copy numbers in both BAL and serum samples were associated with fatal outcomes. Remarkably, the highest and earliest viral loads after initiation of mechanical ventilation support were increased in the non-survival group. Our results imply that viral loads in the lungs contribute to COVID-19 disease severity, while blood titers correlate with lung virus titers, albeit at a lower level. Moreover, they suggest that BAL SARS-CoV-2 copy number quantification at ICU admission may provide a predictive parameter of clinical COVID-19 outcomes. Full article
(This article belongs to the Special Issue State-of-the-Art Virology Research in Croatia 2022)
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11 pages, 2137 KiB  
Article
Virome of Ixodes ricinus, Dermacentor reticulatus, and Haemaphysalis concinna Ticks from Croatia
by Stephen Sameroff, Rafal Tokarz, Marko Vucelja, Komal Jain, Alexandra Oleynik, Marko Boljfetić, Linda Bjedov, Rachel A. Yates, Josip Margaletić, Christopher A. L. Oura, Walter Ian Lipkin, Lidija Cvetko Krajinović and Alemka Markotić
Viruses 2022, 14(5), 929; https://doi.org/10.3390/v14050929 - 29 Apr 2022
Cited by 7 | Viewed by 2356
Abstract
Tick-borne diseases are a serious threat to both public and veterinary health. In this study, we used high-throughput sequencing to characterize the virome of three tick species implicated in the spread of vector-borne disease throughout Croatia. Ten viruses were identified, including seven potential [...] Read more.
Tick-borne diseases are a serious threat to both public and veterinary health. In this study, we used high-throughput sequencing to characterize the virome of three tick species implicated in the spread of vector-borne disease throughout Croatia. Ten viruses were identified, including seven potential novel species within the viral families Flaviviridae, Nyamiviridae, Rhabdoviridae, Peribunyaviridae, Phenuiviridae, and Nairoviridae. Full article
(This article belongs to the Special Issue State-of-the-Art Virology Research in Croatia 2022)
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16 pages, 17261 KiB  
Article
Human Adenovirus Type 26 Induced IL-6 Gene Expression in an αvβ3 Integrin- and NF-κB-Dependent Manner
by Davor Nestić, Ksenija Božinović, Isabela Drašković, Alen Kovačević, Jolien van den Bosch, Jelena Knežević, Jerome Custers, Andreja Ambriović-Ristov and Dragomira Majhen
Viruses 2022, 14(4), 672; https://doi.org/10.3390/v14040672 - 24 Mar 2022
Cited by 2 | Viewed by 2343
Abstract
The low seroprevalent human adenovirus type 26 (HAdV26)-based vaccine vector was the first adenovirus-based vector to receive marketing authorization from European Commission. HAdV26-based vaccine vectors induce durable humoral and cellular immune responses and, as such, represent a highly valuable tool for fighting infectious [...] Read more.
The low seroprevalent human adenovirus type 26 (HAdV26)-based vaccine vector was the first adenovirus-based vector to receive marketing authorization from European Commission. HAdV26-based vaccine vectors induce durable humoral and cellular immune responses and, as such, represent a highly valuable tool for fighting infectious diseases. Despite well-described immunogenicity in vivo, the basic biology of HAdV26 still needs some refinement. The aim of this study was to determine the pro-inflammatory cytokine profile of epithelial cells infected with HAdV26 and then investigate the underlying molecular mechanism. The expression of studied genes and proteins was assessed by quantitative polymerase chain reaction, western blot, and enzyme-linked immunosorbent assay. Confocal microscopy was used to visualize HAdV26 cell uptake. We found that HAdV26 infection in human epithelial cells triggers the expression of pro-inflammatory cytokines and chemokines, namely IL-6, IL-8, IL-1β, and TNF-α, with the most pronounced difference shown for IL-6. We investigated the underlying molecular mechanism and observed that HAdV26-induced IL-6 gene expression is αvβ3 integrin dependent and NF-κB mediated. Our findings provide new data regarding pro-inflammatory cytokine and chemokine expression in HAdV26-infected epithelial cells, as well as details concerning HAdV26-induced host signaling pathways. Information obtained within this research increases our current knowledge of HAdV26 basic biology and, as such, can contribute to further development of HAdV26-based vaccine vectors. Full article
(This article belongs to the Special Issue State-of-the-Art Virology Research in Croatia 2022)
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