Virus-Host Interaction: From Physiology to Pathology

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Virology".

Deadline for manuscript submissions: closed (31 December 2020) | Viewed by 101311

Special Issue Editors


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Guest Editor
Department of Biomedical, Surgical and Dental Sciences, University of Milan, Via Pascal, 36, 20133 Milano, Italy
Interests: polyomaviruses; neurotropic viruses; viruses and tumors; viruses and central nervous diseases; human endogenous eetroviruses; viruses in immunosuppressed hosts
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy
Interests: human polyomaviruses epidemiology and replication in the immunocompromised hosts; viral infections in renal transplantation recipients
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Department of Medical Sciences, University of Trieste, Trieste, Italy
Interests: microbioma and host interaction; human polyomaviruses infection in children population

Special Issue Information

Dear Colleagues,

We invite submissions to a Special Issue on the topic “Virus–Host Interaction: From Physiology to Pathology”.

  • Virus-host interaction is defined as how viruses sustain themselves within the host organisms on a molecular, cellular or population level.
  • Virus–host interaction is a complex phenomenon, often virus- and host cell-specific.
  • The dynamic interactions between a virus and its host are critical for the establishment of acute infections and/or the maintenance of persistent infections, and for the manifestation of the disease.
  • The mechanisms underlying the relationship between the virus and the host are also body district-specific.

We are particularly interested in papers aiming to describe virus–host interaction within the nervous system, the urogenital tract, and all virus–host interaction exiting in cell transformation.

Reviews, meta-analyses, original research, and tutorials focused on methods and techniques will be considered.

Prof. Dr. Pasquale Ferrante
Prof. Dr. Serena Delbue
Prof. Dr. Manola Comar
Guest Editors

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Published Papers (16 papers)

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Research

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12 pages, 1262 KiB  
Article
Lactobacillus iners and gasseri, Prevotella bivia and HPV Belong to the Microbiological Signature Negatively Affecting Human Reproduction
by Giuseppina Campisciano, Valerio Iebba, Gabriella Zito, Stefania Luppi, Monica Martinelli, Leo Fischer, Francesco De Seta, Giuseppe Basile, Giuseppe Ricci and Manola Comar
Microorganisms 2021, 9(1), 39; https://doi.org/10.3390/microorganisms9010039 - 25 Dec 2020
Cited by 23 | Viewed by 3442
Abstract
Infertile couples undergoing the use of assisted reproductive technology are a good study model to evaluate the microbiological signatures affecting reproductive health. We tested vaginal lavages, follicular fluids, embryo culture mediums, and seminal fluids from 47 couples for their microbiome composition and HPV [...] Read more.
Infertile couples undergoing the use of assisted reproductive technology are a good study model to evaluate the microbiological signatures affecting reproductive health. We tested vaginal lavages, follicular fluids, embryo culture mediums, and seminal fluids from 47 couples for their microbiome composition and HPV infection. Twenty-five infertile couples were diagnosed with unexplained infertility, whereas 22 were diagnosed with explained infertility. Lactobacilli were dominant in the vaginal lavages of both patient groups, and the most abundant species was L. iners (CST III), which is linked to a decreased fertility rate. Besides this, L. gasseri—which is known to be associated with oocyte DNA fragmentation and decreased sperm mobility—was identified in the seminal fluids, follicular fluids, and embryo culture media of the unexplained infertility group. Prevotella was increased in the seminal fluids of the explained infertility group, along with HPV-positive seminal fluids: an infection commonly associated with infertility, especially male infertility. Prevotella has been described to negatively affect sperm motility. Taken together, these results suggest that the profiling of the reproductive tract microbiome can add new perspectives to human reproduction. Full article
(This article belongs to the Special Issue Virus-Host Interaction: From Physiology to Pathology)
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25 pages, 9416 KiB  
Article
The HIV-1 Transgenic Rat: Relevance for HIV Noninfectious Comorbidity Research
by Frank Denaro, Francesca Benedetti, Myla D. Worthington, Giovanni Scapagnini, Christopher C. Krauss, Sumiko Williams, Joseph Bryant, Harry Davis, Olga S. Latinovic and Davide Zella
Microorganisms 2020, 8(11), 1643; https://doi.org/10.3390/microorganisms8111643 - 23 Oct 2020
Cited by 6 | Viewed by 2649
Abstract
HIV noninfectious comorbidities (NICMs) are a current healthcare challenge. The situation is further complicated as there are very few effective models that can be used for NICM research. Previous research has supported the use of the HIV-1 transgenic rat (HIV-1TGR) as a model [...] Read more.
HIV noninfectious comorbidities (NICMs) are a current healthcare challenge. The situation is further complicated as there are very few effective models that can be used for NICM research. Previous research has supported the use of the HIV-1 transgenic rat (HIV-1TGR) as a model for the study of HIV/AIDS. However, additional studies are needed to confirm whether this model has features that would support NICM research. A demonstration of the utility of the HIV-1TGR model would be to show that the HIV-1TGR has cellular receptors able to bind HIV proteins, as this would be relevant for the study of cell-specific tissue pathology. In fact, an increased frequency of HIV receptors on a specific cell type may increase tissue vulnerability since binding to HIV proteins would eventually result in cell dysfunction and death. Evidence suggests that observations of selective cellular vulnerability in this model are consistent with some specific tissue vulnerabilities seen in NICMs. We identified CXCR4-expressing cells in the brain, while specific markers for neuronal degeneration demonstrated that the same neural types were dying. We also confirm the presence of gp120 and Tat by immunocytochemistry in the spleen, as previously reported. However, we observed very rare positive cells in the brain. This underscores the point that gp120, which has been reported as detected in the sera and CSF, is a likely source to which these CXCR4-positive cells are exposed. This alternative appears more probable than the local production of gp120. Further studies may indicate some level of local production, but that will not eliminate the role of receptor-mediated pathology. The binding of gp120 to the CXCR4 receptor on neurons and other neural cell types in the HIV-1TGR can thus explain the phenomena of selective cell death. Selective cellular vulnerability may be a contributing factor to the development of NICMs. Our data indicate that the HIV-1TGR can be an effective model for the studies of HIV NICMs because of the difference in the regional expression of CXCR4 in rat tissues, thus leading to specific organ pathology. This also suggests that the model can be used in the development of therapeutic options. Full article
(This article belongs to the Special Issue Virus-Host Interaction: From Physiology to Pathology)
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18 pages, 6350 KiB  
Article
High Prevalence of Human Polyomavirus 7 in Cholangiocarcinomas and Adjacent Peritumoral Hepatocytes: Preliminary Findings
by Faisal Klufah, Ghalib Mobaraki, Emil Chteinberg, Raed A. Alharbi, Véronique Winnepenninckx, Ernst Jan M. Speel, Dorit Rennspiess, Steven W. Olde Damink, Ulf P. Neumann, Anna Kordelia Kurz, Iryna Samarska and Axel zur Hausen
Microorganisms 2020, 8(8), 1125; https://doi.org/10.3390/microorganisms8081125 - 27 Jul 2020
Cited by 11 | Viewed by 3037
Abstract
Cholangiocarcinoma (CCA) is a rare biliary-duct malignancy with poor prognosis. Recently, the presence of the human polyomavirus 6 (HPyV6) has been reported in the bile of diverse hepatobiliary diseases, particularly in the bile of CCA patients. Here, we investigated the presence of novel [...] Read more.
Cholangiocarcinoma (CCA) is a rare biliary-duct malignancy with poor prognosis. Recently, the presence of the human polyomavirus 6 (HPyV6) has been reported in the bile of diverse hepatobiliary diseases, particularly in the bile of CCA patients. Here, we investigated the presence of novel HPyVs in CCA tissues using diverse molecular techniques to assess a possible role of HPyVs in CCA. Formalin-Fixed Paraffin-Embedded (FFPE) tissues of 42 CCA patients were included in this study. PCR-based screening for HPyVs was conducted using degenerated and HPyV-specific primers. Following that, we performed FISH, RNA in situ hybridization (RNA-ISH), and immunohistochemistry (IHC) to assess the presence of HPyVs in selected tissues. Of all 42 CCAs, 25 (59%) were positive for one HPyV, while 10 (24%) CCAs were positive for 2 HPyVs simultaneously, and 7 (17%) were negative for HPyVs. Of the total 35 positive CCAs, 19 (45%) were positive for HPyV7, 4 (9%) for HPyV6, 2 (5%) for Merkel cell polyomavirus (MCPyV), 8 (19%) for both HPyV7/MCPyV, and 2 (5%) for both HPyV6/HPyV7 as confirmed by sequencing. The presence of viral nucleic acids was confirmed by specific FISH, while the RNA-ISH confirmed the presence of HPyV6 on the single-cell level. In addition, expression of HPyV7, HPyV6, and MCPyV proteins were confirmed by IHC. Our results strongly indicate that HPyV7, HPyV6, and MCPyV infect bile duct epithelium, hepatocytes, and CCA cells, which possibly suggest an indirect role of these viruses in the etiopathogenesis of CCA. Furthermore, the observed hepatotropism of these novel HPyV, in particular HPyV7, might implicate a role of these viruses in other hepatobiliary diseases. Full article
(This article belongs to the Special Issue Virus-Host Interaction: From Physiology to Pathology)
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20 pages, 4446 KiB  
Article
Human Metapneumovirus Establishes Persistent Infection in Lung Microvascular Endothelial Cells and Primes a Th2-Skewed Immune Response
by Antonella Bugatti, Stefania Marsico, Manuela Fogli, Sara Roversi, Serena Messali, Daniela Bosisio, Cinzia Giagulli, Arnaldo Caruso, Silvano Sozzani, Simona Fiorentini and Francesca Caccuri
Microorganisms 2020, 8(6), 824; https://doi.org/10.3390/microorganisms8060824 - 30 May 2020
Cited by 3 | Viewed by 2105
Abstract
Human Metapneumovirus (HMPV) is a major cause of lower respiratory tract infections. HMPV infection has been hypothesized to alter dendritic cell (DC) immune response; however, many questions regarding HMPV pathogenesis within the infected lung remain unanswered. Here, we show that HMPV productively infects [...] Read more.
Human Metapneumovirus (HMPV) is a major cause of lower respiratory tract infections. HMPV infection has been hypothesized to alter dendritic cell (DC) immune response; however, many questions regarding HMPV pathogenesis within the infected lung remain unanswered. Here, we show that HMPV productively infects human lung microvascular endothelial cells (L-HMVECs). The release of infectious virus occurs for up to more than 30 days of culture without producing overt cytopathic effects and medium derived from persistently HMPV-infected L-HMVECs (secretome) induced monocyte-derived DCs to prime naïve CD4 T-cells toward a Th2 phenotype. Moreover, we demonstrated that infected secretomes trigger DCs to up-regulate OX40L expression and OX40L neutralization abolished the pro-Th2 effect that is induced by HMPV-secretome. We clarified secretome from HMPV by size exclusion and ultracentrifugation with the aim to characterize the role of viral particles in the observed pro-Th2 effect. In both cases, the percentage of IL-4-producing cells and expression of OX40L returned at basal levels. Finally, we showed that HMPV, per se, could reproduce the ability of secretome to prime pro-Th2 DCs. These results suggest that HMPV, persistently released by L-HMVECs, might take part in the development of a skewed, pro-Th2 lung microenvironment. Full article
(This article belongs to the Special Issue Virus-Host Interaction: From Physiology to Pathology)
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13 pages, 255 KiB  
Article
Viruses of Respiratory Tract: an Observational Retrospective Study on Hospitalized Patients in Rome, Italy
by Marco Ciotti, Massimo Maurici, Viviana Santoro, Luigi Coppola, Loredana Sarmati, Gerardo De Carolis, Patrizia De Filippis and Francesca Pica
Microorganisms 2020, 8(4), 501; https://doi.org/10.3390/microorganisms8040501 - 01 Apr 2020
Cited by 10 | Viewed by 2998
Abstract
Respiratory tract infections account for high morbidity and mortality around the world. Fragile patients are at high risk of developing complications such as pneumonia and may die from it. Limited information is available on the extent of the circulation of respiratory viruses in [...] Read more.
Respiratory tract infections account for high morbidity and mortality around the world. Fragile patients are at high risk of developing complications such as pneumonia and may die from it. Limited information is available on the extent of the circulation of respiratory viruses in the hospital setting. Most knowledge relates to influenza viruses (FLU) but several other viruses produce flu-like illness. The study was conducted at the University Hospital Policlinico Tor Vergata, Rome, Italy. Clinical and laboratory data from hospitalized patients with respiratory tract infections during the period October 2016–March 2019 were analysed. The retrospective analysis included 17 viral agents detected by FilmArray test and clinical data from medical records and hospital discharge sheets. Models were adjusted for relevant confounders such as clinical severity and risk of death, socio-demographic characteristics and surgical procedures. From a total of 539 specimens analysed, 180 (33.39%) were positive for one or more respiratory viruses. Among them, 83 (46.1 %) were positive for influenza viruses (FLU), 36 (20%) rhino/enteroviruses (RHV/EV), 17 (9.44%) human coronaviruses (HCOV-229E, -HKU1, -NL63, and -OC43), 17 (9.44%) respiratory syncytial virus, 15 (8.33%) human metapneumovirus (HMPV), 8 (4.44%) parainfluenza viruses (PIV) and 4 (2.22%) adenoviruses (ADV). The distribution of viral agents varied across age groups and month of detection. The positive specimens were from 168 patients [102 M, 66 F; median age (range): 64 years (19−93)]. Overall, 40% of them had a high-grade clinical severity and a 27% risk of death; 27 patients died and 22 of them (81.5%) had received a clinical diagnosis of pneumonia. Respiratory viral infections may have a severe course and a poor prognosis in hospitalized patients, due to underlying comorbidities. Monitoring the circulation of respiratory viruses in hospital settings is important to improve diagnosis, prevention and treatment. Full article
(This article belongs to the Special Issue Virus-Host Interaction: From Physiology to Pathology)
9 pages, 243 KiB  
Article
The Obesity-Related Gut Bacterial and Viral Dysbiosis Can Impact the Risk of Colon Cancer Development
by Giuseppina Campisciano, Nicolò de Manzini, Serena Delbue, Carolina Cason, Davide Cosola, Giuseppe Basile, Pasquale Ferrante, Manola Comar and Silvia Palmisano
Microorganisms 2020, 8(3), 431; https://doi.org/10.3390/microorganisms8030431 - 19 Mar 2020
Cited by 22 | Viewed by 3749
Abstract
An incorrect food regimen from childhood is suggested to negatively impact the gut microbiome composition leading to obesity and perhaps to colon rectal cancer (CRC) in adults. In this study, we show that the obesity and cancer gut microbiota share a characteristic microbial [...] Read more.
An incorrect food regimen from childhood is suggested to negatively impact the gut microbiome composition leading to obesity and perhaps to colon rectal cancer (CRC) in adults. In this study, we show that the obesity and cancer gut microbiota share a characteristic microbial profile with a high colonization by mucin degraders species, such as Hafnia alvei and Akkermansia muciniphila. In addition, the species Clostridium bolteae, a bacterium associated with insulin resistance, dyslipidemia, and inflammation, has been associated with the presence of oncogenic Human Polyomaviruses (HPyVs). Merkel cell Polyomavirus (MCPyV) and BK Polyomavirus (BKPyV) were the most frequently oncogenic viruses recovered in the gut of both obese and tumor patients. Considering the high seroprevalence of HPyVs in childhood, their association with specific bacterial species deserve to be further investigated. Data from the present study highlight the presence of a similar microbiome pattern in CRC and obese subjects, suggesting that obese microbiome may represent an opportunity for tumorigenic/driver bacteria and viruses to trigger cell transformation. Full article
(This article belongs to the Special Issue Virus-Host Interaction: From Physiology to Pathology)
12 pages, 941 KiB  
Article
The Importance of Transaminases Flare in Liver Elastography: Characterization of the Probability of Liver Fibrosis Overestimation by Hepatitis C Virus-Induced Cytolysis
by Mauro Giuffrè, Sofia Fouraki, Manola Comar, Flora Masutti and Lory Saveria Crocè
Microorganisms 2020, 8(3), 348; https://doi.org/10.3390/microorganisms8030348 - 29 Feb 2020
Cited by 30 | Viewed by 2957
Abstract
Background: Liver stiffness measurement (LSM) is crucial for appropriate fibrosis staging in patients with ongoing hepatitis C virus (HCV) infection. However, there is still an ongoing debate on the impact of serum transaminases (aspartate-aminotransferase, AST; alanine-aminotransferase, ALT) on LSM. Methods: We selected 110 [...] Read more.
Background: Liver stiffness measurement (LSM) is crucial for appropriate fibrosis staging in patients with ongoing hepatitis C virus (HCV) infection. However, there is still an ongoing debate on the impact of serum transaminases (aspartate-aminotransferase, AST; alanine-aminotransferase, ALT) on LSM. Methods: We selected 110 patients undergoing HCV eradication therapy with LSM compatible with significant liver fibrosis. LSM was evaluated prior to therapy and one year after HCV eradication. Results: LSM showed a median decrease of 35% from baseline values, and 67 (61%) patients showed posttreatment values compatible with lower fibrosis stages. We developed two logistic regression models to determine the probability of liver fibrosis overestimation according to serum transaminase. The probability of overestimation of two or more fibrosis grade is equal to (1) 50% for AST of 99 IU/L (2.2 ULN) and ALT of 90.5 IU/L (2 ULN), (2) 80% for AST of 123.5 IU/L (2.74 ULN) and ALT of 101.5 IU/L (2.25 ULN), and (3) reaches 100% for AST of 211 IU/L (4.7 ULN) and ALT of 140 IU/L (3.1 ULN). Conclusions: This study highlights the impact of serum transaminases on LSM. We believe that our findings may serve as a reference point for appropriate fibrosis stratification by liver elastography in patients with HCV infection. Full article
(This article belongs to the Special Issue Virus-Host Interaction: From Physiology to Pathology)
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18 pages, 2175 KiB  
Article
HHV-6A Infection and Systemic Sclerosis: Clues of a Possible Association
by Elisabetta Caselli, Irene Soffritti, Maria D’Accolti, Daria Bortolotti, Roberta Rizzo, Gianluca Sighinolfi, Dilia Giuggioli and Clodoveo Ferri
Microorganisms 2020, 8(1), 39; https://doi.org/10.3390/microorganisms8010039 - 24 Dec 2019
Cited by 24 | Viewed by 3258
Abstract
Systemic sclerosis (SSc) is an autoimmune disease characterized by vasculopathy, excessive extracellular matrix deposition, and fibrosis of the skin and internal organs. Several infectious agents, including human herpesvirus-6 (HHV-6), have been suggested as possible triggering factors, but a direct association is still missing. [...] Read more.
Systemic sclerosis (SSc) is an autoimmune disease characterized by vasculopathy, excessive extracellular matrix deposition, and fibrosis of the skin and internal organs. Several infectious agents, including human herpesvirus-6 (HHV-6), have been suggested as possible triggering factors, but a direct association is still missing. We characterized 26 SSc patients for the presence of HHV-6 in tissues and blood, the anti-HHV-6 response, HLA-G plasma levels, and KIR typing. Given the prominent role of endothelial cells (EC) in SSc pathogenesis, along with HHV-6 tropism for EC, we also investigated the expression of pro-fibrosis factors in HHV-6 infected EC. Results showed the presence of HHV-6A in skin biopsies, and an increased virus load was associated with disease severity and poor natural killer (NK) response against the virus, particularly in subjects exhibiting a KIR2 phenotype. HLA-G plasma levels were significantly higher in HHV-6A/B-KIR2 positive SSc patients and in vitro HHV-6A infection-induced pro-fibrosis factors expression in EC, supporting its role in the development of the fibrosing process. Our data suggest an association between virus infection/reactivation and disease, opening the way to future studies to understand the mechanisms by which HHV-6A might contribute to the multifactorial pathogenesis of SSc. Full article
(This article belongs to the Special Issue Virus-Host Interaction: From Physiology to Pathology)
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11 pages, 1592 KiB  
Article
Human Polyomaviruses in the Cerebrospinal Fluid of Neurological Patients
by Serena Delbue, Diego Franciotta, Sara Giannella, Maria Dolci, Lucia Signorini, Rosalia Ticozzi, Sarah D’Alessandro, Giuseppina Campisciano, Manola Comar, Pasquale Ferrante and Marco Ciotti
Microorganisms 2020, 8(1), 16; https://doi.org/10.3390/microorganisms8010016 - 20 Dec 2019
Cited by 10 | Viewed by 2366
Abstract
Background: Central nervous system (CNS) infections by human polyomaviruses (HPyVs), with the exception of JC (JCPyV), have been poorly studied. Methods: In total, 234 cerebrospinal fluid (CSF) samples were collected from patients affected with neurological disorders. DNA was isolated and subjected to quantitative [...] Read more.
Background: Central nervous system (CNS) infections by human polyomaviruses (HPyVs), with the exception of JC (JCPyV), have been poorly studied. Methods: In total, 234 cerebrospinal fluid (CSF) samples were collected from patients affected with neurological disorders. DNA was isolated and subjected to quantitative real-time PCR (Q-PCR) for the detection of six HPyVs: JCPyV, BKPyV, Merkel cell PyV (MCPyV), HPyV6, HPyV7, and HPyV9. Where possible, the molecular characterization of the viral strains was carried out by nested PCR and automated sequencing. Results: JCPyV was detected in 3/234 (1.3%), BKPyV in 15/234 (6.4%), MCPyV in 22/234 (9.4%), and HPyV6 in 1/234 (0.4%) CSF samples. JCPyV was detected at the highest (p < 0.05) mean load (3.7 × 107 copies/mL), followed by BKPyV (1.9 × 106 copies/mL), MCPyV (1.9 × 105 copies/mL), and HPyV6 (3.3 × 104 copies/mL). The noncoding control regions (NCCRs) of the sequenced viral strains were rearranged. Conclusions: HPyVs other than JCPyV were found in the CSF of patients affected with different neurological diseases, probably as bystanders, rather than etiological agents of the disease. However, the fact that they can be latent in the CNS should be considered, especially in immunosuppressed patients. Full article
(This article belongs to the Special Issue Virus-Host Interaction: From Physiology to Pathology)
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14 pages, 2113 KiB  
Article
Oncogenic Virome Benefits from the Different Vaginal Microbiome-Immune Axes
by Giuseppina Campisciano, Tarik Gheit, Francesco De Seta, Carolina Cason, Nunzia Zanotta, Serena Delbue, Giuseppe Ricci, Pasquale Ferrante, Massimo Tommasino and Manola Comar
Microorganisms 2019, 7(10), 414; https://doi.org/10.3390/microorganisms7100414 - 01 Oct 2019
Cited by 9 | Viewed by 3117
Abstract
The picture of dynamic interaction between oncogenic viruses and the vaginal bacteria-immune host milieu is incomplete. We evaluated the impact of Polyomaviridae, Papillomaviridae, and Herpesviridae oncoviruses on the vaginal Community State Types (CSTs) and host immune response in reproductive-age women. In [...] Read more.
The picture of dynamic interaction between oncogenic viruses and the vaginal bacteria-immune host milieu is incomplete. We evaluated the impact of Polyomaviridae, Papillomaviridae, and Herpesviridae oncoviruses on the vaginal Community State Types (CSTs) and host immune response in reproductive-age women. In our cohort, only Polyomaviridae and Papillomaviridae were detected and were associated with changes in the resident bacteria of CST I and IV (p < 0.05). Lactobacillus crispatus increased in CST I while Prevotella timonensis and Sneathia sanguinegens increased in CST IV. Conversely, CST II and III showed an alteration of the immune response, with the decrease of Eotaxin, MCP-1, IL-7, IL-9, and IL-15 (p < 0.05), leading to reduced antiviral efficacy. An efficient viral clearance was observed only in women from CST I, dominated by Lactobacillus crispatus. Our in vivo study begins to address the knowledge gap with respect to the role of vaginal bacteria and immune response in susceptibility to oncoviral infections. Full article
(This article belongs to the Special Issue Virus-Host Interaction: From Physiology to Pathology)
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Review

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15 pages, 620 KiB  
Review
Human Herpesvirus 8 and Host-Cell Interaction: Long-Lasting Physiological Modifications, Inflammation and Related Chronic Diseases
by Fabrizio Angius, Angela Ingianni and Raffaello Pompei
Microorganisms 2020, 8(3), 388; https://doi.org/10.3390/microorganisms8030388 - 11 Mar 2020
Cited by 3 | Viewed by 4126
Abstract
Oncogenic and latent-persistent viruses belonging to both DNA and RNA groups are known to cause serious metabolism alterations. Among these, the Human Herpesvirus 8 (HHV8) infection induces stable modifications in biochemistry and cellular metabolism, which in turn affect its own pathological properties. HHV8 [...] Read more.
Oncogenic and latent-persistent viruses belonging to both DNA and RNA groups are known to cause serious metabolism alterations. Among these, the Human Herpesvirus 8 (HHV8) infection induces stable modifications in biochemistry and cellular metabolism, which in turn affect its own pathological properties. HHV8 enhances the expression of insulin receptors, supports the accumulation of neutral lipids in cytoplasmic lipid droplets and induces alterations in both triglycerides and cholesterol metabolism in endothelial cells. In addition, HHV8 is also known to modify immune response and cytokine production with implications for cell oxidative status (i.e., reactive oxygen species activation). This review underlines the recent findings regarding the role of latent and persistent HHV8 viral infection in host physiology and pathogenesis. Full article
(This article belongs to the Special Issue Virus-Host Interaction: From Physiology to Pathology)
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16 pages, 1703 KiB  
Review
Measles: An Overview of a Re-Emerging Disease in Children and Immunocompromised Patients
by Andrea Misin, Roberta Maria Antonello, Stefano Di Bella, Giuseppina Campisciano, Nunzia Zanotta, Daniele Roberto Giacobbe, Manola Comar and Roberto Luzzati
Microorganisms 2020, 8(2), 276; https://doi.org/10.3390/microorganisms8020276 - 18 Feb 2020
Cited by 40 | Viewed by 24218
Abstract
Despite the availability of a safe and effective vaccine, in 2018, around 350,000 measles cases were reported worldwide, which resulted in an estimate of 142,300 deaths from measles. Additionally, in 2017, global measles cases spiked, causing the death of 110,000 people, mostly children [...] Read more.
Despite the availability of a safe and effective vaccine, in 2018, around 350,000 measles cases were reported worldwide, which resulted in an estimate of 142,300 deaths from measles. Additionally, in 2017, global measles cases spiked, causing the death of 110,000 people, mostly children under the age of 5 years and immunocompromised adults. The increase in measles incidence is caused by the ongoing reduction of vaccination coverage. This event has triggered public and scientific interest. For this reason, we reviewed the pathophysiology of measles infection, focusing on mechanisms by which the virus spreads systemically through the host organism. By reaching the lymphocytes from the airways through a “trojan horse” strategy, measles induces an immunosuppression status. H and F glycoproteins, both expressed in the envelope, ensure attachment of the virus to host cells and spreading from one cell to another by binding to several receptors, as described in detail. The severity of the disease depends both on the age and underlying conditions of patients as well as the social and health context in which epidemics spread, and is often burdened by sequelae and complications that may occur several years after infection. Particular attention was paid to special groups that are more susceptible to severe or atypical measles. An overview of microbiology, symptoms, diagnosis, prevention, and treatment completes and enriches the review. Full article
(This article belongs to the Special Issue Virus-Host Interaction: From Physiology to Pathology)
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13 pages, 747 KiB  
Review
In Vitro Zika Virus Infection of Human Neural Progenitor Cells: Meta-Analysis of RNA-Seq Assays
by Rossella Gratton, Paola Maura Tricarico, Almerinda Agrelli, Heverton Valentim Colaço da Silva, Lucas Coêlho Bernardo, Sergio Crovella, Antonio Victor Campos Coelho, Ronald Rodrigues de Moura and Lucas André Cavalcanti Brandão
Microorganisms 2020, 8(2), 270; https://doi.org/10.3390/microorganisms8020270 - 17 Feb 2020
Cited by 13 | Viewed by 4183
Abstract
The Zika virus (ZIKV) is an emergent arthropod-borne virus (arbovirus) responsible for congenital Zika syndrome (CZS) and a range of other congenital malformations. Evidence shows that ZIKV infects human neural progenitor cells (hNPCs) in the fetal brain, prompting inflammation and tissue damage/loss. Despite [...] Read more.
The Zika virus (ZIKV) is an emergent arthropod-borne virus (arbovirus) responsible for congenital Zika syndrome (CZS) and a range of other congenital malformations. Evidence shows that ZIKV infects human neural progenitor cells (hNPCs) in the fetal brain, prompting inflammation and tissue damage/loss. Despite recent advances, little is known about the pathways involved in CZS pathogenesis. We performed a meta-analysis, gene ontology (GO), and pathway analysis of whole transcriptome studies with the aim of clarifying the genes and pathways potentially altered during hNPCs infection with ZIKV. We selected three studies (17 samples of infected hPNCs compared to hPNCs uninfected controls) through a systematic search of the Gene Expression Omnibus (GEO) database. The raw reads were trimmed, counted, and normalized. Next, we performed a rank product meta-analysis to detect consistently differentially expressed genes (DEGs) in these independent experiments. We detected 13 statistically significant DEGs. GO ontology and reactome analysis showed an enrichment of interferon, pro-inflammatory, and chemokines signaling and apoptosis pathways in ZIKV-infected cells. Moreover, we detected three possible new candidate genes involved in hNPCs infection: APOL6, XAF1, and TNFRSF1. Our results confirm that interferon (IFN) signaling dominates the ZIKV response, and that a crucial contribution is given by apoptotic pathways, which might elicit the CZS phenotype. Full article
(This article belongs to the Special Issue Virus-Host Interaction: From Physiology to Pathology)
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26 pages, 707 KiB  
Review
The Use of Antimalarial Drugs against Viral Infection
by Sarah D’Alessandro, Diletta Scaccabarozzi, Lucia Signorini, Federica Perego, Denise P. Ilboudo, Pasquale Ferrante and Serena Delbue
Microorganisms 2020, 8(1), 85; https://doi.org/10.3390/microorganisms8010085 - 08 Jan 2020
Cited by 118 | Viewed by 21971
Abstract
In recent decades, drugs used to treat malaria infection have been shown to be beneficial for many other diseases, including viral infections. In particular, they have received special attention due to the lack of effective antiviral drugs against new emerging viruses (i.e., HIV, [...] Read more.
In recent decades, drugs used to treat malaria infection have been shown to be beneficial for many other diseases, including viral infections. In particular, they have received special attention due to the lack of effective antiviral drugs against new emerging viruses (i.e., HIV, dengue virus, chikungunya virus, Ebola virus, etc.) or against classic infections due to drug-resistant viral strains (i.e., human cytomegalovirus). Here, we reviewed the in vitro/in vivo and clinical studies conducted to evaluate the antiviral activities of four classes of antimalarial drugs: Artemisinin derivatives, aryl-aminoalcohols, aminoquinolines, and antimicrobial drugs. Full article
(This article belongs to the Special Issue Virus-Host Interaction: From Physiology to Pathology)
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19 pages, 1405 KiB  
Review
PYHIN Proteins and HPV: Role in the Pathogenesis of Head and Neck Squamous Cell Carcinoma
by Giuseppe Riva, Matteo Biolatti, Giancarlo Pecorari, Valentina Dell’Oste and Santo Landolfo
Microorganisms 2020, 8(1), 14; https://doi.org/10.3390/microorganisms8010014 - 20 Dec 2019
Cited by 15 | Viewed by 5984
Abstract
In the last decades, the human papillomavirus (HPV) emerged as an etiological cause of head and neck squamous cell carcinoma (HNSCC), especially in the oropharynx. The role of two intracellular DNA sensors, which belong to the PYHIN family (interferon-inducible protein 16 (IFI16) and [...] Read more.
In the last decades, the human papillomavirus (HPV) emerged as an etiological cause of head and neck squamous cell carcinoma (HNSCC), especially in the oropharynx. The role of two intracellular DNA sensors, which belong to the PYHIN family (interferon-inducible protein 16 (IFI16) and absent in melanoma 2 protein (AIM2)), has been analyzed in relation to HPV infection and head and neck carcinogenesis. In particular, IFI16 and AIM2 expression depends on HPV infection in HNSCC. They represent viral restriction factors and are key components of the intrinsic immunity activated against different viruses, including HPV. This review analyzed and summarized the recent findings about the role of PYHIN proteins in HPV+ and HPV HNSCC. Full article
(This article belongs to the Special Issue Virus-Host Interaction: From Physiology to Pathology)
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23 pages, 788 KiB  
Review
Dendritic Cells/Macrophages-Targeting Feature of Ebola Glycoprotein and its Potential as Immunological Facilitator for Antiviral Vaccine Approach
by Titus Abiola Olukitibi, Zhujun Ao, Mona Mahmoudi, Gary A. Kobinger and Xiaojian Yao
Microorganisms 2019, 7(10), 402; https://doi.org/10.3390/microorganisms7100402 - 29 Sep 2019
Cited by 12 | Viewed by 4122
Abstract
In the prevention of epidemic and pandemic viral infection, the use of the antiviral vaccine has been the most successful biotechnological and biomedical approach. In recent times, vaccine development studies have focused on recruiting and targeting immunogens to dendritic cells (DCs) and macrophages [...] Read more.
In the prevention of epidemic and pandemic viral infection, the use of the antiviral vaccine has been the most successful biotechnological and biomedical approach. In recent times, vaccine development studies have focused on recruiting and targeting immunogens to dendritic cells (DCs) and macrophages to induce innate and adaptive immune responses. Interestingly, Ebola virus (EBOV) glycoprotein (GP) has a strong binding affinity with DCs and macrophages. Shreds of evidence have also shown that the interaction between EBOV GP with DCs and macrophages leads to massive recruitment of DCs and macrophages capable of regulating innate and adaptive immune responses. Therefore, studies for the development of vaccine can utilize the affinity between EBOV GP and DCs/macrophages as a novel immunological approach to induce both innate and acquired immune responses. In this review, we will discuss the unique features of EBOV GP to target the DC, and its potential to elicit strong immune responses while targeting DCs/macrophages. This review hopes to suggest and stimulate thoughts of developing a stronger and effective DC-targeting vaccine for diverse virus infection using EBOV GP. Full article
(This article belongs to the Special Issue Virus-Host Interaction: From Physiology to Pathology)
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