Uberto Pozzoli

Uberto Pozzoli
IRCCS Eugenio Medea · Neurobiology

About

189
Publications
14,708
Reads
How we measure 'reads'
A 'read' is counted each time someone views a publication summary (such as the title, abstract, and list of authors), clicks on a figure, or views or downloads the full-text. Learn more
4,240
Citations
Additional affiliations
January 1998 - present
IRCCS Eugenio Medea
Position
  • Research Director

Publications

Publications (189)
Article
Full-text available
Primate herpes simplex viruses are species-specific and relatively harmless to their natural hosts. However, cross-species transmission is often associated with severe disease, as exemplified by the virulence of macacine herpesvirus 1 (B virus) in humans. We performed a genome-wide scan for signals of adaptation of simplexviruses to their hominin h...
Article
Full-text available
Four endemic coronaviruses infect humans and cause mild symptoms. Because previous analyses were based on a limited number of sequences and did not control for effects that affect molecular dating, we re-assessed the timing of endemic coronavirus emergence. After controlling for recombination, selective pressure, and molecular clock model, we obtai...
Article
The aim of the study was to assess the contribution of negative emotionality at 3 months (T1) and serotonin transporter gene (SLC6A4) DNA methylation at 4.5 years of age (T2) to emotion regulation in pre‐schoolers born very preterm and full‐term. Forty one children (n = 21 born very preterm, n = 20 born full‐term) participated in the study. Fretful...
Article
Full-text available
Four coronaviruses (HCoV-OC43, HCoV-HKU1, HCoV-NL63, and HCoV-229E) are endemic in human populations. All these viruses are seasonal and generate short-term immunity. Like the highly pathogenic coronaviruses, the endemic coronaviruses have zoonotic origins. Thus, understanding the evolutionary dynamics of these human viruses might provide insight i...
Article
Centromeres have central functions in chromosome segregation, but centromeric DNA and centromere‐binding proteins evolve rapidly in most eukaryotes. The selective pressure(s) underlying the fast evolution of centromere‐binding proteins are presently unknown. An attractive possibility is that selfish centromeres promote their preferential inclusion...
Preprint
Full-text available
Understanding the evolutionary dynamics of the four human endemic coronaviruses might provide insight into the future trajectories of SARS-CoV-2 evolution. We re-assessed the timing of endemic coronavirus emergence and we show that all viruses entered human populations in a time-frame ranging from ~500 to 55 years ago. Because the three highly path...
Article
Full-text available
Analysis of the bat viruses most closely related to SARS‐CoV‐2 indicated that the virus probably required limited adaptation to spread in humans. Nonetheless, since its introduction in human populations, SARS‐CoV‐2 must have been subject to the selective pressure imposed by the human immune system. We exploited the availability of a large number of...
Article
Background Children with attention deficit hyperactivity disorder (ADHD) exhibit behavioral inhibition deficits, which often lead to emotional dysregulation (ED) affecting individual ability to control emotions and behavioral responses. In ADHD, ED is associated with poor outcomes and comorbidities, with both externalizing and internalizing disorde...
Preprint
Full-text available
Primate herpes simplex viruses are relatively harmless to their natural hosts, whereas cross-species transmission can result in severe disease. We performed a genome-wide scan for signals of adaptation of simplexviruses to hominins. We found evidence of positive selection in three glycoproteins, with selected sites located in antigenic determinants...
Preprint
Full-text available
The ongoing evolution of SARS-CoV-2 is expected to be at least partially driven by the selective pressure imposed by the human immune system. We exploited the availability of a large number of high-quality SARS-CoV-2 genomes, as well as of validated epitope predictions, to show that B cell epitopes in the spike glycoprotein (S) and in the nucleocap...
Article
Full-text available
Whereas the majority of herpesviruses co-speciated with their mammalian hosts, human herpes simplex virus 2 (HSV-2, genus Simplexvirus) most likely originated from the cross-species transmission of chimpanzee herpesvirus 1 to an ancestor of modern humans. We exploited the peculiar evolutionary history of HSV-2 to investigate the selective events th...
Article
Full-text available
Cytomegaloviruses (order Herpesvirales) display remarkable species-specificity as a result of long-term co-evolution with their mammalian hosts. Human cytomegalovirus (HCMV) is exquisitely adapted to our species and displays high genetic diversity. We leveraged information on inter-species divergence of primate-infecting cytomegaloviruses and intra...
Article
Full-text available
Human betaherpesviruses 6A and 6B (HHV-6A and HHV-6B) are highly prevalent in human populations. The genomes of these viruses can be stably integrated at the telomeres of human chromosomes and be vertically transmitted (inherited chromosomally integrated HHV-6A/HHV-6B, iciHHV-6A/iciHHV-6B). We reconstructed the population structures of HHV-6A and H...
Article
Herpes simplex viruses types 1 and 2 (HSV-1 and HSV-2) are ubiquitous human pathogens. Both viruses evolved from simplexviruses infecting African primates and they are thus thought to have left Africa during early human migrations. We analyzed the population structure of HSV-1 and HSV-2 circulating strains. Results indicated that HSV-1 populations...
Article
Human betaherpesviruses 6A and 6B (HHV-6A and HHV-6B) are highly prevalent in human populations. The genomes of these viruses can be stably integrated at the telomeres of human chromosomes and be vertically transmitted (inherited chromosomally integrated HHV-6, iciHHV6). We reconstructed the population structure of HHV-6 and we show that HHV-6A gen...
Article
JC polyomavirus (JCPyV) is one of the most prevalent human viruses. Findings based on the geographic distribution of viral subtypes suggested that JCPyV co-diverged with human populations. This view was however challenged by data reporting a much more recent origin and expansion of JCPyV. We collected information on ∼1,100 worldwide strains and we...
Article
Full-text available
Spinal muscular atrophy is a motor neuron disorder caused by mutations in SMN1. The reasons for the selective vulnerability of motor neurons linked to SMN (encoded by SMN1) reduction remain unclear. Therefore, we performed deep RNA sequencing on human spinal muscular atrophy motor neurons to detect specific altered gene splicing/expression and to i...
Article
Full-text available
Telomeres protect the ends of eukaryotic chromosomes and are essential for cell viability. In mammals, telomere dynamics vary with life history traits (e.g. body mass and longevity), suggesting differential selection depending on physiological characteristics. Telomeres, in analogy to centromeric regions, also represent candidate meiotic drivers an...
Article
Full-text available
Hepatitis C virus (HCV) belongs to the Hepacivirus genus and is genetically heterogeneous, with seven major genotypes further divided into several recognized subtypes. HCV origin was previously dated in a range between ∼200 and 1000 years ago. Hepaciviruses have been identified in several domestic and wild mammals, the largest viral diversity being...
Article
Full-text available
The Mammarenavirus genus includes several pathogenic species of rodent-borne viruses. Old World (OW) mammarenaviruses infect rodents in the Murinae subfamily and are mainly transmitted in Africa and Asia; New World (NW) mammarenaviruses are found in rodents of the Cricetidae subfamily in the Americas. We applied a selection-informed method to estim...
Article
Very preterm (VPT) infants (gestational age < 32 weeks) require long-lasting hospitalization in the Neonatal Intensive Care Unit (NICU), even in absence of severe morbidities. During NICU stay, life-saving interventions occur and include invasive and painful skin-breaking procedures (NICU-related stress), which constitute a major early adverse expe...
Article
Full-text available
Very preterm (VPT) infants admitted to Neonatal Intensive Care Unit (NICU) are at risk for altered brain growth and less-than-optimal socio-emotional development. Recent research suggests that early NICU-related stress contributes to socio-emotional impairments in VPT infants at 3 months through epigenetic regulation (i.e., DNA methylation) of the...
Data
CpG sites position on the chromosome 17 and distance from the transcription start site of the SLC6A4 gene. Note. Chr17 = Chromosome 17; TSS = Transcriptional Start Site. (DOCX)
Data
Exploratory path analysis for the mediation effect of ATL-MPL (A), ATL-LPR (B), and ATL-LPL (C) on the relationship between birth-to-discharge SLC6A4 methylation increase and GMDS Personal-Social score at 12 months CA. Note. NICU, Neonatal Intensive Care Unit; Δmet, mean change in SLC6A4 methylation from birth to NICU discharge at CpG chr17: 285627...
Data
This data set reports all relevant data for the present paper. (XLSX)
Article
Full-text available
In addition to high intelligence, humans evolved specialized social-cognitive skills, which are specifically affected in children with autism spectrum disorder (ASD). Genes affected in ASD represent suitable candidates to study the evolution of human social cognition. We performed an evolutionary analysis on 68 genes associated to neurodevelopmenta...
Article
Full-text available
The Old World (OW) arenavirus complex includes several species of rodent-borne viruses, some of which (i.e., Lassa virus, LASV and Lymphocytic choriomeningitis virus, LCMV) cause human diseases. Most LCMV and LASV infections are caused by rodent-to-human transmissions. Thus, viral evolution is largely determined by events that occur in the wildlife...
Article
Background Very preterm (VPT) infants are hospitalized in Neonatal Intensive Care Units (NICUs) and are exposed to life-saving procedures eliciting pain-related stress. Recent research documented that pain-related stress might result in birth-to-discharge increased methylation of serotonin transporter gene (SLC6A4) in VPT infants, leading to poorer...
Article
Filovirus infection is mediated by engagement of the surface-exposed glycoprotein (GP) by its cellular receptor, NPC1 (Niemann-Pick C1). Two loops in the C domain of NPC1 (NPC1-C) bind filovirus GP. Herein we show that filovirus GP and NPC1-C evolve under mutual selective pressure. Analysis of a large mammalian phylogeny indicated that strong funct...
Article
Aim: The present study is part of a prospective micro-longitudinal research project and reports on the association between SLC6A4 methylation and socio-emotional stress response in very preterm (VPT) and full-term (FT) infants. Materials & methods: SLC6A4 methylation was assessed at birth and discharge in 32 VPT infants, and at birth in 27 FT in...
Poster
Full-text available
Background. Recent research has highlighted that procedural pain during the Neonatal Intensive Care Unit (NICU) might associate with altered DNA methylation of the gene encoding for serotonin transporter (SLC6A4) in very preterm (VPT) infants (Provenzi et al., 2015). These alterations have been shown to differ from full-term (FT) infants at birth a...
Article
Full-text available
Myosin VI functions in endocytosis and cell motility. Alternative splicing of myosin VI mRNA generates two distinct isoform types, myosin VIshort and myosin VIlong, which differ in the C-terminal region. Their physiological and pathological roles remain unknown. Here we identified an isoform-specific regulatory helix, named the α2-linker, that defi...
Article
Full-text available
Humans possess a communication system based on spoken and written language. Other animals can learn vocalization by imitation, but this is not equivalent to human language. Many genes were described to be implicated in language impairment (LI) and developmental dyslexia (DD), but their evolutionary history has not been thoroughly analyzed. Herein w...
Article
The complement system is an innate immunity effector mechanism its action is antagonized by a wide array of pathogens and complement evasion determines the virulence of several infections. We investigated the evolutionary history of the complement system and of bacterial-encoded complement-interacting proteins. Complement components targeted by sev...
Article
Preterm birth and Neonatal Intensive Care Unit (NICU) stay are early adverse stressful experiences, which may result in an altered temperamental profile. The serotonin transporter gene (SLC6A4), which has been linked to infant temperament, is susceptible to epigenetic regulation associated with early stressful experience. This study examined a mode...
Article
Importance: Both SARS-CoV and MERS-CoV originated in bats and spread to humans via an intermediate host. This clearly highlights the potential for coronavirus host shifting and the relevance of understanding the molecular events underling the adaptation to new host species. We investigated the evolution of ORF1a and ORF1b in lineage C betaCoVs and...
Article
Full-text available
Middle East respiratory syndrome coronavirus (MERS-CoV) originated in bats and spread to humans via zoonotic transmission from camels. We analyzed the evolution of the spike (S) gene in betacoronaviruses (betaCoVs) isolated from different mammals, in bat coronavirus populations, as well as in MERS-CoV strains from the current outbreak. Results indi...
Article
Full-text available
Dietary shifts can drive molecular evolution in mammals and a major transition in human history, the agricultural revolution, favored carbohydrate consumption. We investigated the evolutionary history of 9 genes encoding brush-border proteins involved in carbohydrate digestion/absorption. Results indicated widespread adaptive evolution in mammals,...
Article
Plasmodium falciparum, the causative agent of the deadliest form of malaria, is a member of the Laverania subgenus, which includes ape-infecting parasites. P. falciparum is thought to have originated in gorillas, although infection is now restricted to humans. Laverania parasites display remarkable host-specificity, which is partially mediated by t...
Article
Very preterm (VPT) infants need long-lasting hospitalization in the Neonatal Intensive Care Unit (NICU) during which they are daily exposed to pain-related stress. Alterations of DNA methylation at the promoter region of the SLC6A4 have been associated with early adverse experiences in infants. The main aim of the present work was to investigate th...
Article
Full-text available
OAS (2'-5'-oligoadenylate synthases) proteins and cyclic GMP-AMP synthase (cGAS, gene symbol: MB21D1) patrol the cytoplasm for the presence of foreign nucleic acids. Upon binding to dsRNA or dsDNA, OAS proteins and cGAS produce nucleotide second messengers to activate RNase L and STING (stimulator of interferon genes, gene symbol: TMEM173), respect...
Article
A-to-I RNA editing operated by ADAR enzymes is extremely common in mammals. Several editing events in coding regions have pivotal physiological roles and affect protein sequence (recoding events) or function. We analyzed the evolutionary history of the 3 ADAR family genes and of their coding targets. Evolutionary analysis indicated that ADAR evolve...