Distribution of human Cytomegalovirus gB genotypes in samples from pediatric patients in Parma during the period 1995-2003

Background. Human Cytomegalovirus (HCMV) infection is a leading cause of developmental disability and late neurological sequelae in children. Several literature data indicate that HCMV pericapsidic glycoprotein B (gB) is highly immunogenic and is involved in virus-cell interaction.The gB gene has hypervariable regions producing four genotypes (gB1, gB2, gB3, gB4); however, the correlation between gB genotypes and HCMV infection outcome remains unclear. Objectives. The main goal of this study was that of evaluating the distribution of HCMV gB genotypes in samples from pediatric population in Parma with congenital, perinatal or post-natal infections, in order to find a correlation between viral gB genotypes and the clinical outcome of the infection. Study design. Forty eight urine samples, selected between 1999 and 2003 and stored at -80°C, underwent DNA extraction, nested PCR amplification of a gB gene region and restriction polymorphism analysis (RFLP). Results. The gB genotypes distribution in the considered pediatric population was as follows: gB1 was the most diffused (45.83%) followed by gB2 (22.92%), gB3 (16.67%) and gB4 (14.58%). Conclusions. In the considered population, gB1 was the most represented genotype and was often found in congenital and perinatal symptomatic infections, as well as in post-natal, asymptomatic infections

Possibile mechanisms of cellular response to the cytomegalovirus lytic infection in a simil-macrophagic cell model in vitro

In corso di infezione da citomegalovirus umano (HCMV), un adatto stato metabolico della cellula è fondamentale per garantire al virus di portare a termine una efficace infezione produttiva. Per questo motivo HCMV ha sviluppato diverse strategie per alterare il metabolismo della cellula ospite al fine di creare le condizioni più favorevoli per la propria replicazione. In particolare, è nota la capacità del virus di interferire con il ciclo cellulare, provocandone generalmente il blocco in G1-G1/S in cellule proliferanti. Le finalità principali di questo studio sono state quelle di valutare la possibile azione di interferenza sul ciclo cellulare da parte di HCMV ed i possibili meccanismi che ne sono alla base in cellule irreversibilmente uscite dal ciclo cellulare. A tale scopo, sono stati utilizzati monociti THP-1 differenziati a macrofagi; anche in questo caso è stata dimostrata un’azione di interferenza da parte di HCMV sul ciclo cellulare, che si estrinseca spingendo tali cellule, inizialmente ferme in G0, verso la fase S. Per quel che riguarda i possibili meccanismi utilizzati dal virus, la parallela osservazione dell’attivazione del “Toll-like receptor” (TLR) 4 in corso di infezione virale e i dati recenti di letteratura che supportano il suo ruolo nell’indurre la proliferazione cellulare, hanno successivamente orientato lo studio alla verifica di un coinvolgimento di questo recettore nel mediare l’azione virus-indotta sul ciclo cellulare. A tale scopo, sono stati utilizzati due specifici antagonisti di TLR4 (che intervengono su due differenti fasi del “pathway” metabolico da esso attivato) per studiare l’efficienza dell’infezione virale e l’effetto di interferenza virus-indotta sul ciclo cellulare. I dati ricavati da questo studio supportano l’ipotesi di un coinvolgimento di TLR4 quale possibile meccanismo cooptato dal virus per l’espletamento di un’efficiente ciclo replicativo litico in macrofagi THP-1.A suitable metabolic state of the cell is fundamental for a productive infection with human cytomegalovirus (HCMV). In particular, it is known that this virus is able to interfere with the cell cycle regulation, principally by inducing a blockade of proliferating cells in G1-G1/S phases. This study aimed at deepening our knowledge on the HCMV ability to develop a lytic cycle in a cellular model irreversibly withdrawn from the cell cycle and on the possible mechanisms used by the virus to accomplish a successful replication. To this end, we used THP-1 monocytes differentiated to macrophages and demonstrated that, in this case too, HCMV is able to deregulate the cell cycle, pushing these cells, arrested in G0, towards the S phase. As to the possible mechanisms underlying these observations, the parallel results demonstrating the Toll-like receptor (TLR) 4 activation following HCMV infection of THP-1 macrophages, and the literature data describing TLR4 as involved in the cell cycle deregulation, let us investigate the possible involvement of TLR4 in the cell cycle alteration observed in HCMV-infected THP-1 macrophages. To this end, two specific TLR4 antagonists (acting on different steps of the metabolic pathway activated by this receptor) were used. Their effects were evaluated by checking the effectiveness of virus infection, as well as the virus-induced activation of the cell cycle. Our data support the notion of a role of TLR4 in favouring the development of an efficient viral lytic cycle in THP-1 macrophages

HIV‐1, HAART and cancer: a complex relationship

International audienc

Rôle des facteurs infectieux et environnementaux dans l'oncogenèse du Lymphome de Burkitt endémique

International audienc

A Comparison of Techniques to Evaluate the Effectiveness of Genome Editing

International audienc

Distribution of human Cytomegalovirus gB genotypes in samples from pediatric patients in Parma during the period 1995-2003

Background. Human Cytomegalovirus (HCMV) infection is a leading cause of developmental disability and late neurological sequelae in children. Several literature data indicate that HCMV pericapsidic glycoprotein B (gB) is highly immunogenic and is involved in virus-cell interaction.The gB gene has hypervariable regions producing four genotypes (gB1, gB2, gB3, gB4); however, the correlation between gB genotypes and HCMV infection outcome remains unclear. Objectives. The main goal of this study was that of evaluating the distribution of HCMV gB genotypes in samples from pediatric population in Parma with congenital, perinatal or post-natal infections, in order to find a correlation between viral gB genotypes and the clinical outcome of the infection. Study design. Forty eight urine samples, selected between 1999 and 2003 and stored at -80°C, underwent DNA extraction, nested PCR amplification of a gB gene region and restriction polymorphism analysis (RFLP). Results. The gB genotypes distribution in the considered pediatric population was as follows: gB1 was the most diffused (45.83%) followed by gB2 (22.92%), gB3 (16.67%) and gB4 (14.58%). Conclusions. In the considered population, gB1 was the most represented genotype and was often found in congenital and perinatal symptomatic infections, as well as in post-natal, asymptomatic infections

Factors That Affect the Formation of Chromosomal Translocations in Cells

Chromosomal translocations are products of the illegitimate repair of DNA double-strand breaks (DSBs). Their formation can bring about significant structural and molecular changes in the cell that can be physiologically and pathologically relevant. The induced changes may lead to serious and life-threatening diseases such as cancer. As a growing body of evidence suggests, the formation of chromosomal translocation is not only affected by the mere close spatial proximity of gene loci as potential translocation partners. Several factors may affect formation of chromosomal translocations, including chromatin motion to the potential sources of DSBs in the cell. While these can be apparently random events, certain chromosomal translocations appear to be cell-type-specific. In this review, we discuss how chromosomal translocations are formed and explore how different cellular factors contribute to their formation

Metal ions modify DNA-protecting and mutagen-scavenging capacities of the AV-153 1,4-dihydropyridine

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