Special Issue "Features of Pathogenesis of Human Viral Infections and Antiviral Drugs"

A special issue of Medicina (ISSN 1648-9144).

Deadline for manuscript submissions: closed (1 December 2019).

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Special Issue Editor

Prof. Dr. Stefano Aquaro
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Guest Editor
Department of Pharmacy, Health, and Nutritional Sciences, University of Calabria, Rende, Italy
Interests: virus evolution; macrophages; HIV pathogenesis; antivirals; HIV chemotherapy; neuroAIDS; mechanisms of virus entry; chemokines and chemokine receptors; role of astrocytes and neurones in HIV infection
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Special Issue Information

Dear Colleagues,

Among infectious diseases, viral infections are the leading cause of death worldwide, especially in the most low-income countries, particularly in young children. Most of the human viruses are all well characterized in terms of structure, life-cycle, tropism, and associated primary pathologies, but many of the pathogenetic mechanisms underlying their ability to cause acute infection, persist or reactivate in the host and cause chronic and/or degenerative damage, and still need to be fully clarified. At the same time, it seems necessary to develop novel therapeutic approaches and rationale, and possibly more potent antiviral compounds that are addressed to novel targets. All researchers working in the fields of human viral infections and antiviral drugs are cordially invited to contribute original research papers or reviews to this Special Issue of Medicina.

Prof. Dr. Stefano Aquaro
Guest Editor

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Keywords

  • Viruses
  • Virus pathogenesis
  • Antivirals
  • Drug design
  • Antiviral activity
  • Antiviral resistance
  • Virus evolution
  • Antiviral therapy
  • Virus entry
  • Virus replication
  • Viral enzymes

Published Papers (6 papers)

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Research

Article
The Relationship between the Soluble Receptor for Advanced Glycation End Products and Oxidative Stress in Patients with Palmoplantar Warts
Medicina 2019, 55(10), 706; https://0-doi-org.brum.beds.ac.uk/10.3390/medicina55100706 - 20 Oct 2019
Cited by 3 | Viewed by 987
Abstract
Background and objectives: Warts are the most common lesions caused by human papillomavirus (HPV). Recent research suggests that oxidative stress and inflammation are involved in the pathogenesis of HPV-related lesions. It has been shown that the soluble receptor for advanced glycation end [...] Read more.
Background and objectives: Warts are the most common lesions caused by human papillomavirus (HPV). Recent research suggests that oxidative stress and inflammation are involved in the pathogenesis of HPV-related lesions. It has been shown that the soluble receptor for advanced glycation end products (sRAGE) may act as a protective factor against the deleterious effects of inflammation and oxidative stress, two interconnected processes. However, in HPV infection, the role of sRAGE, constitutively expressed in the skin, has not been investigated in previous studies. Materials and Methods: In order to analyze the role of sRAGE in warts, we investigated the link between sRAGE and the inflammatory response on one hand, and the relationship between sRAGE and the total oxidant/antioxidant status (TOS/TAS) on the other hand, in both patients with palmoplantar warts (n = 24) and healthy subjects as controls (n = 28). Results: Compared to the control group, our results showed that patients with warts had lower levels of sRAGE (1036.50 ± 207.60 pg/mL vs. 1215.32 ± 266.12 pg/mL, p < 0.05), higher serum levels of TOS (3.17 ± 0.27 vs. 2.93 ± 0.22 µmol H2O2 Eq/L, p < 0.01), lower serum levels of TAS (1.85 ± 0.12 vs. 2.03 ± 0.14 µmol Trolox Eq/L, p < 0.01) and minor variations of the inflammation parameters (high sensitivity-CRP, interleukin-6, fibrinogen, and erythrocyte sedimentation rate). Moreover, in patients with warts, sRAGE positively correlated with TAS (r = 0.43, p < 0.05), negatively correlated with TOS (r = −0.90, p < 0.01), and there was no significant correlation with inflammation parameters. There were no significant differences regarding the studied parameters between groups when we stratified the patients according to the number of the lesions and disease duration. Conclusions: Our results suggest that sRAGE acts as a negative regulator of oxidative stress and could represent a mediator involved in the development of warts. However, we consider that the level of sRAGE cannot be used as a biomarker for the severity of warts. To the best of our knowledge, this is the first study to demonstrate that sRAGE could be involved in HPV pathogenesis and represent a marker of oxidative stress in patients with warts. Full article
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Article
Hepatitis B Virus Genotypes in the Kingdom of Bahrain: Prevalence, Gender Distribution and Impact on Hepatic Biomarkers
Medicina 2019, 55(10), 622; https://0-doi-org.brum.beds.ac.uk/10.3390/medicina55100622 - 23 Sep 2019
Cited by 3 | Viewed by 1076
Abstract
Background: Approximately 400 million people are infected with Hepatitis B virus (HBV) around the world, which makes it one of the world’s major infectious diseases. The prevalence of HBV genotypes and predictive factors for risk are poorly known in the Kingdom of [...] Read more.
Background: Approximately 400 million people are infected with Hepatitis B virus (HBV) around the world, which makes it one of the world’s major infectious diseases. The prevalence of HBV genotypes and predictive factors for risk are poorly known in the Kingdom of Bahrain. Objectives: The aim of the present study was to investigate the prevalence of HBV genotypes, its correlation with demographic factor sand impacts on hepatic biomarkers. Materials and Methods: Venous blood samples were collected from 82 HBV positive patients (48 males, 34 females). The extraction of HBV DNA, PCR amplification, and genotyping were done to classify different genotypes (A, A/D, B, B/D, C, D, D/E, E). HBV genotypes association with gender, nationality, mode of transmission, and liver cirrhosis complication was determined by descriptive statistic and univariate analysis of variance (ANOVA). For liver function test, unpaired t-test and ANOVA were performed. Results: The predominant genotype among patients under study was genotype D (61%), followed by genotype A (10%), and lowest frequency was found for undetermined genotype (1%). In general, there was no significant association between the different genotypes and some demographical factors, serological investigations, and liver function test. The prevalence of HBV genotypes was higher in male patients as compared to female patients and higher in non-Bahraini than in Bahraini. Patients with the dominant genotype D showed higher than the normal maximum range for alanine aminotransferase (ALT) (mean = 45.89) and Gamma-glutamyl transferase (GGT) (mean = 63.36). Conclusions: The most common HBV genotype in Bahrain was genotype D, followed by genotype A. Further studies involving the sources of transmission and impact of hepatic biomarker in Bahrain are required to enhance the control measures of HBV infections. Full article
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Article
Antiviral Activity of Exopolysaccharides Produced by Lactic Acid Bacteria of the Genera Pediococcus, Leuconostoc and Lactobacillus against Human Adenovirus Type 5
Medicina 2019, 55(9), 519; https://0-doi-org.brum.beds.ac.uk/10.3390/medicina55090519 - 22 Aug 2019
Cited by 14 | Viewed by 1659
Abstract
Background and objectives: The use of antagonistic probiotic microorganisms and their byproducts represents a promising approach for the treatment of viral diseases. In the current work, the effect of exopolysaccharides (EPSs) produced by lactic acid bacteria from different genera on the structural [...] Read more.
Background and objectives: The use of antagonistic probiotic microorganisms and their byproducts represents a promising approach for the treatment of viral diseases. In the current work, the effect of exopolysaccharides (EPSs) produced by lactic acid bacteria from different genera on the structural and functional characteristics of cells and the development of adenoviral infection in vitro was studied. Materials and Methods: Cytotoxicity of six EPSs of lactic acid bacteria of the genera Lactobacillus, Leuconostoc and Pediococcus was determined by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay. The influence of the EPSs on the infectivity of human adenovirus type 5 (HAdV-5) and on the cell cycle under a condition of adenovirus infection was studied using plaque reduction assay and flow cytometric analysis, respectively. Results: It was shown that exopolysaccharides were non-toxic to Madin-Darby bovine kidney cells (MDBK) as they reduced their viability by 3–17%. A change in the distribution of the cell cycle phases in the non-infected cell population treated with EPSs was observed. The analysis demonstrated an increase in the number of cells in the S phase by 47% when using EPSs 15a and a decrease in the number of cells in the G1 phase by 20–27% when treated with the EPSs 15a, 33a, and 19s. The use of EPSs did not led to the normalization of the life cycle of HAdV-5 infected cells to the level of non-infected cells. The EPSs showed low virucidal activity and reduced the HAdV-5 infectivity to 85%. Among the studied exopolysaccharides, anti-adenovirus activity was found for EPS 26a that is produced by Lactobacillus spp. strain. The treatment of cells with the EPS following virus adsorption completely (100%) suppressed the formation and release of HAdV-5 infectious. Conclusions: EPS 26a possessed distinct anti-HAdV-5 activity and the obtained data demonstrate the potential of using exopolysaccharides as anti-adenoviral agents. Full article
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Article
A Retrospective Study about the Impact of Switching from Nested PCR to Multiplex Real-Time PCR on the Distribution of the Human Papillomavirus (HPV) Genotypes
Medicina 2019, 55(8), 418; https://0-doi-org.brum.beds.ac.uk/10.3390/medicina55080418 - 30 Jul 2019
Cited by 7 | Viewed by 1147
Abstract
Background and objectives: Human papillomavirus (HPV) is the most prevalent etiological agent of viral sexually-transmitted infection. This study retrospectively evaluated the impact of a switch to a real-time PCR assay in the HPV prevalence and genotypes distribution by a quasi-experimental before-and-after approach. Materials [...] Read more.
Background and objectives: Human papillomavirus (HPV) is the most prevalent etiological agent of viral sexually-transmitted infection. This study retrospectively evaluated the impact of a switch to a real-time PCR assay in the HPV prevalence and genotypes distribution by a quasi-experimental before-and-after approach. Materials and Methods: In total, 1742 samples collected from 1433 patients were analyzed at the UOC Microbiology and Virology of Policlinico of Bari, Italy. HPV DNA detection was performed using initially nested PCR and subsequently multiplex real-time PCR assay. Results: Statistically significant difference in HPV overall prevalence after the introduction of the real-time assay was not detected (48.97% vs. 50.62%). According to different extraction-DNA amplification methods, differences were observed in the prevalence rates of HPV-45, 68, 40, 42, and 43. The lowest prevalence for HPV-45 was observed in the Magna Pure-Real Time PCR group, while HPV-68, 40, 42, and 43 were less observed in the Qiagen-Real Time PCR group. After, a multivariate logistic regression, an increase in the prevalence of HPV-42 (aOR: 4.08, 95% CI: 1.71–9.73) was associated with the multiplex real-time PCR assay. Conclusions: Although this study is a not a direct comparison between two diagnostic methods because it has a sequential structure, it serves to verify the impact of a new molecular assay on HPV distribution. Moreover, the stability of HPV prevalence over time suggests that the population composition and the behavioral variables did not likely change during the observation period. Our study proposes that the introduction of a molecular test for HPV detection may be related to changes of HPV genotypes distribution. Full article
Article
Different Patterns of HIV-1 Replication in MACROPHAGES is Led by Co-Receptor Usage
Medicina 2019, 55(6), 297; https://0-doi-org.brum.beds.ac.uk/10.3390/medicina55060297 - 21 Jun 2019
Cited by 7 | Viewed by 1090
Abstract
Background and objectives: To enter the target cell, HIV-1 binds not only CD4 but also a co-receptor β-chemokine receptor 5 (CCR5) or α chemokine receptor 4 (CXCR4). Limited information is available on the impact of co-receptor usage on HIV-1 replication in monocyte-derived macrophages [...] Read more.
Background and objectives: To enter the target cell, HIV-1 binds not only CD4 but also a co-receptor β-chemokine receptor 5 (CCR5) or α chemokine receptor 4 (CXCR4). Limited information is available on the impact of co-receptor usage on HIV-1 replication in monocyte-derived macrophages (MDM) and on the homeostasis of this important cellular reservoir. Materials and Methods: Replication (measured by p24 production) of the CCR5-tropic 81A strain increased up to 10 days post-infection and then reached a plateau. Conversely, the replication of the CXCR4-tropic NL4.3 strain (after an initial increase up to day 7) underwent a drastic decrease becoming almost undetectable after 10 days post-infection. The ability of CCR5-tropic and CXCR4-tropic strains to induce cell death in MDM was then evaluated. While for CCR5-tropic 81A the rate of apoptosis in MDM was comparable to uninfected MDM, the infection of CXCR4-tropic NL4.3 in MDM was associated with a rate of 14.3% of apoptotic cells at day 6 reaching a peak of 43.5% at day 10 post-infection. Results: This suggests that the decrease in CXCR4-tropic strain replication in MDM can be due to their ability to induce cell death in MDM. The increase in apoptosis was paralleled with a 2-fold increase in the phosphorylated form of p38 compared to WT. Furthermore, microarray analysis showed modulation of proapoptotic and cancer-related genes induced by CXCR4-tropic strains starting from 24 h after infection, whereas CCR5 viruses modulated the expression of genes not correlated with apoptotic-pathways. Conclusions: In conclusion, CXCR4-tropic strains can induce a remarkable depletion of MDM. Conversely, MDM can represent an important cellular reservoir for CCR5-tropic strains supporting the role of CCR5-usage in HIV-1 pathogenesis and as a pharmacological target to contribute to an HIV-1 cure. Full article
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Article
Genotyping of Type A Human Respiratory Syncytial Virus Based on Direct F Gene Sequencing
Medicina 2019, 55(5), 169; https://0-doi-org.brum.beds.ac.uk/10.3390/medicina55050169 - 20 May 2019
Cited by 2 | Viewed by 860
Abstract
Background and objectives: The human respiratory syncytial virus (hRSV) is among the important respiratory pathogens affecting children. Genotype-specific attachment (G) gene sequencing is usually used to determine the virus genotype. The reliability of the fusion (F) gene vs. G gene genotype-specific sequencing was [...] Read more.
Background and objectives: The human respiratory syncytial virus (hRSV) is among the important respiratory pathogens affecting children. Genotype-specific attachment (G) gene sequencing is usually used to determine the virus genotype. The reliability of the fusion (F) gene vs. G gene genotype-specific sequencing was screened. Materials and Methods: Archival RNA from Saudi children who tested positive for hRSV-A were used. Samples were subjected to a conventional one-step RT-PCR for both F and G genes and direct gene sequencing of the amplicons using the same primer sets. Phylogeny and mutational analysis of the obtained sequences were conducted. Results: The generic primer set succeeded to amplify target gene sequences. The phylogenetic tree based on partial F gene sequencing resulted in an efficient genotyping of hRSV-A strains equivalent to the partial G gene genotyping method. NA1, ON1, and GA5 genotypes were detected in the clinical samples. The latter was detected for the first time in Saudi Arabia. Different mutations in both conserved and escape-mutant domains were detected in both F and G. Conclusion: It was concluded that a partial F gene sequence can be used efficiently for hRSV-A genotyping. Full article
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