State-of-the-Art Virology Research in Croatia

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

Deadline for manuscript submissions: closed (31 October 2021) | Viewed by 40298

Special Issue Editors


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

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

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, and are focused 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 of papillomavirus-induced oncogenesis and molecular epidemiology of several human viral pathogens as well as investigations of viral zoonoses and the diversity of plant viruses and subviral pathogens, and their impact on the ecosystems. In addition, Croatia has a scientific center of excellence dedicated towards virology, the Center of Excellence for Viral Immunology and Vaccines, which hosts several research groups at the University of Rijeka and at the University of Zagreb and aims to develop into a vital cornerstone for further development of viral immunology and vaccinology in Croatia. The Center for Excellence's principal activities include studies of 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 COVID-19 pandemics, significant activity in coronaviruses research, mainly supported through specific calls by the Croatian Science Foundation, is taking place in Croatia as well. This Special Issue aims to provide an overview of research in virology and viral pathogenesis within the country, and we invite colleagues to contribute reviews or original research articles related to their research.

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

Manuscript Submission Information

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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 (12 papers)

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Research

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15 pages, 5202 KiB  
Article
Collection of Monoclonal Antibodies Targeting SARS-CoV-2 Proteins
by Marina Pribanić Matešić, Paola Kučan Brlić, Tihana Lenac Roviš, Željka Mačak Šafranko, Abigael Eva Chaouat, Karmela Miklić, Suzana Malić, Nina Ivanković, Maren Schubert, Federico Bertoglio, Alemka Markotić, Ofer Mandelboim, Stipan Jonjić and Ilija Brizić
Viruses 2022, 14(2), 443; https://0-doi-org.brum.beds.ac.uk/10.3390/v14020443 - 21 Feb 2022
Cited by 3 | Viewed by 3078
Abstract
In early 2020, the COVID-19 pandemic sparked a global crisis that continues to pose a serious threat to human health and the economy. Further advancement in research is necessary and requires the availability of quality molecular tools, including monoclonal antibodies. Here, we present [...] Read more.
In early 2020, the COVID-19 pandemic sparked a global crisis that continues to pose a serious threat to human health and the economy. Further advancement in research is necessary and requires the availability of quality molecular tools, including monoclonal antibodies. Here, we present the development and characterization of a collection of over 40 new monoclonal antibodies directed against different SARS-CoV-2 proteins. Recombinant SARS-CoV-2 proteins were expressed, purified, and used as immunogens. Upon development of specific hybridomas, the obtained monoclonal antibody (mAb) clones were tested for binding to recombinant proteins and infected cells. We generated mAbs against structural proteins, the Spike and Nucleocapsid protein, several non-structural proteins (nsp1, nsp7, nsp8, nsp9, nsp10, nsp16) and accessory factors (ORF3a, ORF9b) applicable in flow cytometry, immunofluorescence, or Western blot. Our collection of mAbs provides a set of novel, highly specific tools that will allow a comprehensive analysis of the viral proteome, which will allow further understanding of SARS-CoV-2 pathogenesis and the design of therapeutic strategies. Full article
(This article belongs to the Special Issue State-of-the-Art Virology Research in Croatia)
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20 pages, 1341 KiB  
Article
Population Variability Generated during Rescue Process and Passaging of Recombinant Mumps Viruses
by Anamarija Slović, Tanja Košutić-Gulija, Dubravko Forčić, Maja Šantak, Maja Jagušić, Mirna Jurković, Dorotea Pali and Jelena Ivančić-Jelečki
Viruses 2021, 13(12), 2550; https://0-doi-org.brum.beds.ac.uk/10.3390/v13122550 - 20 Dec 2021
Cited by 2 | Viewed by 2540
Abstract
Recombinant mumps viruses (MuVs) based on established vaccine strains represent attractive vector candidates as they have known track records for high efficacy and the viral genome does not integrate in the host cells. We developed a rescue system based on the consensus sequence [...] Read more.
Recombinant mumps viruses (MuVs) based on established vaccine strains represent attractive vector candidates as they have known track records for high efficacy and the viral genome does not integrate in the host cells. We developed a rescue system based on the consensus sequence of the L-Zagreb vaccine and generated seven different recombinant MuVs by (a) insertion of one or two additional transcription units (ATUs), (b) lengthening of a noncoding region to the extent that the longest noncoding region in MuV genome is created, or (c) replacement of original L-Zagreb sequences with sequences rich in CG and AT dinucleotides. All viruses were successfully rescued and faithfully matched sequences of input plasmids. In primary rescued stocks, low percentages of heterogeneous positions were found (maximum 0.12%) and substitutions were predominantly obtained in minor variants, with maximally four substitutions seen in consensus. ATUs did not accumulate more mutations than the natural MuV genes. Six substitutions characteristic for recombinant viruses generated in our system were defined, as they repetitively occurred during rescue processes. In subsequent passaging of primary rescue stocks in Vero cells, different inconsistencies within quasispecies structures were observed. In order to assure that unwanted mutations did not emerge and accumulate, sub-consensus variability should be closely monitored. As we show for Pro408Leu mutation in L gene and a stop codon in one of ATUs, positively selected variants can rise to frequencies over 85% in only few passages. Full article
(This article belongs to the Special Issue State-of-the-Art Virology Research in Croatia)
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16 pages, 2418 KiB  
Article
Influence of Ribavirin on Mumps Virus Population Diversity
by Mirna Jurković, Anamarija Slović, Dubravko Forčić, Jelena Ivančić-Jelečki, Tanja Košutić-Gulija and Maja Jagušić
Viruses 2021, 13(12), 2535; https://0-doi-org.brum.beds.ac.uk/10.3390/v13122535 - 17 Dec 2021
Cited by 2 | Viewed by 2359
Abstract
Frequent mumps outbreaks in vaccinated populations and the occurrence of neurological complications (e.g., aseptic meningitis or encephalitis) in patients with mumps indicate the need for the development of more efficient vaccines as well as specific antiviral therapies. RNA viruses are genetically highly heterogeneous [...] Read more.
Frequent mumps outbreaks in vaccinated populations and the occurrence of neurological complications (e.g., aseptic meningitis or encephalitis) in patients with mumps indicate the need for the development of more efficient vaccines as well as specific antiviral therapies. RNA viruses are genetically highly heterogeneous populations that exist on the edge of an error threshold, such that additional increases in mutational burden can lead to extinction of the virus population. Deliberate modulation of their natural mutation rate is being exploited as an antiviral strategy and a possibility for rational vaccine design. The aim of this study was to examine the ability of ribavirin, a broad-spectrum antiviral agent, to introduce mutations in the mumps virus (MuV) genome and to investigate if resistance develops during long-term in vitro exposure to ribavirin. An increase in MuV population heterogeneity in the presence of ribavirin has been observed after one passage in cell culture, as well as a bias toward C-to-U and G-to-A transitions, which have previously been defined as ribavirin-related. At higher ribavirin concentration, MuV loses its infectivity during serial passaging and does not recover. At low ribavirin concentration, serial passaging leads to a more significant increase in population diversity and a stronger bias towards ribavirin-related transitions, independently of viral strain or cell culture. In these conditions, the virus retains its initial growth capacity, without development of resistance at a whole-virus population level. Full article
(This article belongs to the Special Issue State-of-the-Art Virology Research in Croatia)
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18 pages, 2453 KiB  
Article
Production- and Purification-Relevant Properties of Human and Murine Cytomegalovirus
by Sanda Ravlić, Marija Brgles, Lea Hiršl, Stipan Jonjić and Beata Halassy
Viruses 2021, 13(12), 2481; https://0-doi-org.brum.beds.ac.uk/10.3390/v13122481 - 10 Dec 2021
Viewed by 2628
Abstract
There is a large unmet need for a prophylactic vaccine against human cytomegalovirus (HCMV) to combat the ubiquitous infection that is ongoing with this pathogen. A vaccination against HCMV could protect immunocompromised patients and prevent birth defects caused by congenital HCMV infections. Moreover, [...] Read more.
There is a large unmet need for a prophylactic vaccine against human cytomegalovirus (HCMV) to combat the ubiquitous infection that is ongoing with this pathogen. A vaccination against HCMV could protect immunocompromised patients and prevent birth defects caused by congenital HCMV infections. Moreover, cytomegalovirus (CMV) has a number of features that make it a very interesting vector platform for gene therapy. In both cases, preparation of a highly purified virus is a prerequisite for safe and effective application. Murine CMV (MCMV) is by far the most studied model for HCMV infections with regard to the principles that govern the immune surveillance of CMVs. Knowledge transfer from MCMV and mice to HCMV and humans could be facilitated by better understanding and characterization of the biological and biophysical properties of both viruses. We carried out a detailed investigation of HCMV and MCMV growth kinetics as well as stability under the influence of clarification and different storage conditions. Further, we investigated the possibilities to concentrate and purify both viruses by ultracentrifugation and ion-exchange chromatography. Defective enveloped particles were not separately analyzed; however, the behavior of exosomes was examined during all experiments. The effectiveness of procedures was monitored using CCID50 assay, Nanoparticle tracking analysis, ELISA for host cell proteins, and quantitative PCR for host cell DNA. MCMV generally proved to be more robust in handling. Despite its greater sensitivity, HCMV was efficiently (100% recovery) purified and concentrated by anion-exchange chromatography using QA monolithic support. The majority of the host genomic DNA as well as most of the host cell proteins were removed by this procedure. Full article
(This article belongs to the Special Issue State-of-the-Art Virology Research in Croatia)
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17 pages, 2143 KiB  
Article
Fast, Reliable, and Simple Point-of-Care-like Adaptation of RT-qPCR for the Detection of SARS-CoV-2 for Use in Hospital Emergency Departments
by Martina Pavletić, Marija Mazor, Mate Lerga, Tatjana Mileta, Jelena Železnjak, Tina Ružić, Sanda Ravlić, Dora Palčevski, Jelena Kirinčić, Silvestar Mežnarić, Ana Mišković, Maja Materljan, Alan Šustić, Berislav Lisnić and Vanda Juranić Lisnić
Viruses 2021, 13(12), 2413; https://0-doi-org.brum.beds.ac.uk/10.3390/v13122413 - 02 Dec 2021
Cited by 1 | Viewed by 3784
Abstract
During COVID-19 pandemics, the availability of testing has often been a limiting factor during patient admissions into the hospital. To circumvent this problem, we adapted an existing diagnostic assay, Seegene Allplex SARS-CoV-2, into a point-of-care-style direct qPCR (POC dqPCR) assay and implemented it [...] Read more.
During COVID-19 pandemics, the availability of testing has often been a limiting factor during patient admissions into the hospital. To circumvent this problem, we adapted an existing diagnostic assay, Seegene Allplex SARS-CoV-2, into a point-of-care-style direct qPCR (POC dqPCR) assay and implemented it in the Emergency Department of Clinical Hospital Center Rijeka, Croatia. In a 4-month analysis, we tested over 10,000 patients and demonstrated that POC-dqPCR is robust and reliable and can be successfully implemented in emergency departments and similar near-patient settings and can be performed by medical personnel with little prior experience in qPCR. Full article
(This article belongs to the Special Issue State-of-the-Art Virology Research in Croatia)
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11 pages, 1143 KiB  
Article
Prevalence and Molecular Characterization of Human Bocavirus Detected in Croatian Children with Respiratory Infection
by Sunčanica Ljubin-Sternak, Anamarija Slović, Maja Mijač, Mirna Jurković, Dubravko Forčić, Irena Ivković-Jureković, Tatjana Tot and Jasmina Vraneš
Viruses 2021, 13(9), 1728; https://0-doi-org.brum.beds.ac.uk/10.3390/v13091728 - 31 Aug 2021
Cited by 9 | Viewed by 2267
Abstract
Human bocavirus (HBoV) 1 is considered an important respiratory pathogen, while the role of HBoV2-4 in clinical disease remains somewhat controversial. Since, they are characterized by a rapid evolution, worldwide surveillance of HBoVs’ genetics is necessary. This study explored the prevalence of HBoV [...] Read more.
Human bocavirus (HBoV) 1 is considered an important respiratory pathogen, while the role of HBoV2-4 in clinical disease remains somewhat controversial. Since, they are characterized by a rapid evolution, worldwide surveillance of HBoVs’ genetics is necessary. This study explored the prevalence of HBoV genotypes in pediatric patients with respiratory tract infection in Croatia and studied their phylogeny. Using multiplex PCR for 15 respiratory viruses, we investigated 957 respiratory samples of children up to 18 years of age with respiratory tract infection obtained from May 2017 to March 2021 at two different hospitals in Croatia. Amplification of HBoV near-complete genome or three overlapping fragments was performed, sequenced, and their phylogenetic inferences constructed. HBoV was detected in 7.6% children with a median age of 1.36 years. Co-infection was observed in 82.2% samples. Sequencing was successfully performed on 29 HBoV positive samples, and all belonged to HBoV1. Croatian HBoV1 sequences are closely related to strains isolated worldwide, and no phylogenetic grouping based on mono- or co-infection cases or year of isolation was observed. Calculated rates of evolution for HBoV1 were 10−4 and 10−5 substitutions per site and year. Recombination was not detected among sequences from this study. Full article
(This article belongs to the Special Issue State-of-the-Art Virology Research in Croatia)
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13 pages, 1857 KiB  
Article
Molecular Characterization of Human Papillomavirus Type 159 (HPV159)
by Iva Marković, Lea Hošnjak, Katja Seme and Mario Poljak
Viruses 2021, 13(8), 1668; https://0-doi-org.brum.beds.ac.uk/10.3390/v13081668 - 23 Aug 2021
Cited by 1 | Viewed by 2143
Abstract
Human papillomavirus type 159 (HPV159) was identified in an anal swab sample and preliminarily genetically characterized by our group in 2012. Here we present a detailed molecular in silico analysis that showed that the HPV159 viral genome is 7443 bp in length and [...] Read more.
Human papillomavirus type 159 (HPV159) was identified in an anal swab sample and preliminarily genetically characterized by our group in 2012. Here we present a detailed molecular in silico analysis that showed that the HPV159 viral genome is 7443 bp in length and divided into five early and two late genes, with conserved functional domains and motifs, and a non-coding long control region (LCR) with significant regulatory sequences that allow the virus to complete its life cycle and infect novel host cells. HPV159, clustering into the cutaneotropic Betapapillomavirus (Beta-PV) genus, is phylogenetically most similar to HPV9, forming an individual phylogenetic group in the viral species Beta-2. After testing a large representative collection of clinical samples with HPV159 type-specific RT-PCR, in addition to the anal canal from which the first HPV159 isolate was obtained, HPV159 was further detected in other muco-cutaneous (4/181, 2.2%), mucosal (22/764, 2.9%), and cutaneous (14/554, 2.5%) clinical samples, suggesting its extensive tissue tropism. However, because very low HPV159 viral loads were estimated in the majority of positive samples, it seemed that HPV159 mainly caused clinically insignificant infections of the skin and mucosa. Using newly developed, highly sensitive HPV159-specific nested PCRs, two additional HPV159 LCR viral variants were identified. Nevertheless, all HPV159 mutations were demonstrated outside important functional domains of the LCR, suggesting that the HPV159 viral variants were most probably not pathogenically different. This complete molecular characterization of HPV159 enhances our knowledge of the genome characteristics, tissue tropism, and phylogenetic diversity of Beta-PVs that infect humans. Full article
(This article belongs to the Special Issue State-of-the-Art Virology Research in Croatia)
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Review

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12 pages, 1658 KiB  
Review
Emerging Trends in the Epidemiology of COVID-19: The Croatian ‘One Health’ Perspective
by Tatjana Vilibic-Cavlek, Vladimir Stevanovic, Diana Brlek-Gorski, Ivana Ferencak, Thomas Ferenc, Magdalena Ujevic-Bosnjak, Irena Tabain, Natasa Janev-Holcer, Ivana Perkovic, Mario Anticevic, Barbara Bekavac, Bernard Kaic, Anna Mrzljak, Marin Ganjto, Ljiljana Zmak, Maja Mauric Maljkovic, Pavle Jelicic, Lovro Bucic and Ljubo Barbic
Viruses 2021, 13(12), 2354; https://0-doi-org.brum.beds.ac.uk/10.3390/v13122354 - 24 Nov 2021
Cited by 11 | Viewed by 3159
Abstract
During the four pandemic waves, a total of 560,504 cases and 10,178 deaths due to COVID-19 were reported in Croatia. The Alpha variant, dominant from March 2021 (>50% of positive samples), was rapidly replaced by Delta variants (>90%) by August 2021. Several seroprevalence [...] Read more.
During the four pandemic waves, a total of 560,504 cases and 10,178 deaths due to COVID-19 were reported in Croatia. The Alpha variant, dominant from March 2021 (>50% of positive samples), was rapidly replaced by Delta variants (>90%) by August 2021. Several seroprevalence studies were conducted in different populations (general population, children/adolescents, professional athletes, healthcare workers, veterinarians) and in immunocompromised patients (hemodialysis patients, liver/kidney transplant recipients). After the first pandemic wave, seroprevalence rates of neutralizing (NT) antibodies were reported to be 0.2–5.5%. Significantly higher seropositivity was detected during/after the second wave, 2.6–18.7%. Two studies conducted in pet animals (February-June 2020/July–December 2020) reported SARS-CoV-2 NT antibodies in 0.76% of cats and 0.31–14.69% of dogs, respectively. SARS-CoV-2 NT antibodies were not detected in wildlife. Environmental samples taken in the households of COVID-19 patients showed high-touch personal objects as most frequently contaminated (17.3%), followed by surfaces in patients’ rooms (14.6%), kitchens (13.3%) and bathrooms (8.3%). SARS-CoV-2 RNA was also detected in 96.8% affluent water samples, while all effluent water samples tested negative. Detection of SARS-CoV-2 in humans, animals and the environment suggests that the ‘One Health’ approach is critical to controlling COVID-19 and future pandemics. Full article
(This article belongs to the Special Issue State-of-the-Art Virology Research in Croatia)
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17 pages, 39001 KiB  
Review
Legacy of Plant Virology in Croatia—From Virus Identification to Molecular Epidemiology, Evolution, Genomics and Beyond
by Dijana Škorić, Silvija Černi, Mirna Ćurković-Perica, Marin Ježić, Mladen Krajačić and Martina Šeruga Musić
Viruses 2021, 13(12), 2339; https://doi.org/10.3390/v13122339 - 23 Nov 2021
Viewed by 2220
Abstract
This paper showcases the development of plant virology in Croatia at the University of Zagreb, Faculty of Science, from its beginning in the 1950s until today, more than 70 years later. The main achievements of the previous and current group members are highlighted [...] Read more.
This paper showcases the development of plant virology in Croatia at the University of Zagreb, Faculty of Science, from its beginning in the 1950s until today, more than 70 years later. The main achievements of the previous and current group members are highlighted according to various research topics and fields. Expectedly, some of those accomplishments remained within the field of plant virology, but others make part of a much-extended research spectrum exploring subviral pathogens, prokaryotic plant pathogens, fungi and their viruses, as well as their interactions within ecosystems. Thus, the legacy of plant virology in Croatia continues to contribute to the state of the art of microbiology far beyond virology. Research problems pertinent for directing the future research endeavors are also proposed in this review. Full article
(This article belongs to the Special Issue State-of-the-Art Virology Research in Croatia)
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14 pages, 959 KiB  
Review
Immunological Mechanisms of Sickness Behavior in Viral Infection
by Mia Krapić, Inga Kavazović and Felix M. Wensveen
Viruses 2021, 13(11), 2245; https://0-doi-org.brum.beds.ac.uk/10.3390/v13112245 - 08 Nov 2021
Cited by 14 | Viewed by 5196
Abstract
Sickness behavior is the common denominator for a plethora of changes in normal behavioral routines and systemic metabolism during an infection. Typical symptoms include temperature, muscle weakness, and loss of appetite. Whereas we experience these changes as a pathology, in fact they are [...] Read more.
Sickness behavior is the common denominator for a plethora of changes in normal behavioral routines and systemic metabolism during an infection. Typical symptoms include temperature, muscle weakness, and loss of appetite. Whereas we experience these changes as a pathology, in fact they are a carefully orchestrated response mediated by the immune system. Its purpose is to optimize immune cell functionality against pathogens whilst minimizing viral replication in infected cells. Sickness behavior is controlled at several levels, most notably by the central nervous system, but also by other organs that mediate systemic homeostasis, such as the liver and adipose tissue. Nevertheless, the changes mediated by these organs are ultimately initiated by immune cells, usually through local or systemic secretion of cytokines. The nature of infection determines which cytokine profile is induced by immune cells and therefore which sickness behavior ensues. In context of infection, sickness behavior is typically beneficial. However, inappropriate activation of the immune system may induce adverse aspects of sickness behavior. For example, tissue stress caused by obesity may result in chronic activation of the immune system, leading to lasting changes in systemic metabolism. Concurrently, metabolic disease prevents induction of appropriate sickness behavior following viral infection, thus impairing the normal immune response. In this article, we will revisit recent literature that elucidates both the benefits and the negative aspects of sickness behavior in context of viral infection. Full article
(This article belongs to the Special Issue State-of-the-Art Virology Research in Croatia)
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31 pages, 1903 KiB  
Review
Human Papillomaviruses-Associated Cancers: An Update of Current Knowledge
by Ena Pešut, Anamaria Đukić, Lucija Lulić, Josipa Skelin, Ivana Šimić, Nina Milutin Gašperov, Vjekoslav Tomaić, Ivan Sabol and Magdalena Grce
Viruses 2021, 13(11), 2234; https://0-doi-org.brum.beds.ac.uk/10.3390/v13112234 - 06 Nov 2021
Cited by 22 | Viewed by 3834
Abstract
Human papillomaviruses (HPVs), which are small, double-stranded, circular DNA viruses infecting human epithelial cells, are associated with various benign and malignant lesions of mucosa and skin. Intensive research on the oncogenic potential of HPVs started in the 1970s and spread across Europe, including [...] Read more.
Human papillomaviruses (HPVs), which are small, double-stranded, circular DNA viruses infecting human epithelial cells, are associated with various benign and malignant lesions of mucosa and skin. Intensive research on the oncogenic potential of HPVs started in the 1970s and spread across Europe, including Croatia, and worldwide. Nowadays, the causative role of a subset of oncogenic or high-risk (HR) HPV types, led by HPV-16 and HPV-18, of different anogenital and head and neck cancers is well accepted. Two major viral oncoproteins, E6 and E7, are directly involved in the development of HPV-related malignancies by targeting synergistically various cellular pathways involved in the regulation of cell cycle control, apoptosis, and cell polarity control networks as well as host immune response. This review is aimed at describing the key elements in HPV-related carcinogenesis and the advances in cancer prevention with reference to past and on-going research in Croatia. Full article
(This article belongs to the Special Issue State-of-the-Art Virology Research in Croatia)
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18 pages, 1339 KiB  
Review
Cytomegalovirus Infection and Inflammation in Developing Brain
by Fran Krstanović, William J. Britt, Stipan Jonjić and Ilija Brizić
Viruses 2021, 13(6), 1078; https://0-doi-org.brum.beds.ac.uk/10.3390/v13061078 - 04 Jun 2021
Cited by 32 | Viewed by 4778
Abstract
Human cytomegalovirus (HCMV) is a highly prevalent herpesvirus that can cause severe disease in immunocompromised individuals and immunologically immature fetuses and newborns. Most infected newborns are able to resolve the infection without developing sequelae. However, in severe cases, congenital HCMV infection can result [...] Read more.
Human cytomegalovirus (HCMV) is a highly prevalent herpesvirus that can cause severe disease in immunocompromised individuals and immunologically immature fetuses and newborns. Most infected newborns are able to resolve the infection without developing sequelae. However, in severe cases, congenital HCMV infection can result in life-threatening pathologies and permanent damage of organ systems that possess a low regenerative capacity. Despite the severity of the problem, HCMV infection of the central nervous system (CNS) remains inadequately characterized to date. Cytomegaloviruses (CMVs) show strict species specificity, limiting the use of HCMV in experimental animals. Infection following intraperitoneal administration of mouse cytomegalovirus (MCMV) into newborn mice efficiently recapitulates many aspects of congenital HCMV infection in CNS. Upon entering the CNS, CMV targets all resident brain cells, consequently leading to the development of widespread histopathology and inflammation. Effector functions from both resident cells and infiltrating immune cells efficiently resolve acute MCMV infection in the CNS. However, host-mediated inflammatory factors can also mediate the development of immunopathologies during CMV infection of the brain. Here, we provide an overview of the cytomegalovirus infection in the brain, local immune response to infection, and mechanisms leading to CNS sequelae. Full article
(This article belongs to the Special Issue State-of-the-Art Virology Research in Croatia)
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