A5007813132- Animal Virus Infections Studies
- Viral Infections and Vectors
- Herpesvirus Infections and Treatments
- Hepatitis C virus research
- Cytomegalovirus and herpesvirus research
- Viral Infections and Outbreaks Research
- Molecular Biology Techniques and Applications
- vaccines and immunoinformatics approaches
- SARS-CoV-2 and COVID-19 Research
- Animal Disease Management and Epidemiology
- HIV Research and Treatment
- Signaling Pathways in Disease
- Plant Virus Research Studies
- Viral gastroenteritis research and epidemiology
- Glycosylation and Glycoproteins Research
- Zoonotic diseases and public health
- Hepatitis B Virus Studies
- Viral Infections and Immunology Research
- Autophagy in Disease and Therapy
- COVID-19 Clinical Research Studies
- Liver Disease Diagnosis and Treatment
- interferon and immune responses
- Bacteriophages and microbial interactions
- Immune Cell Function and Interaction
- Mosquito-borne diseases and control
IRCCS Eugenio Medea
2014-2023
Institute of Bioinformatics
2015
Coronaviruses encode a variable number of accessory proteins that are involved in host-virus interaction, suppression immune responses, or evasion. SARS-CoV-2 encodes at least twelve proteins, whose roles during infection have been studied. Nevertheless, the role ORF3c protein, an alternative open reading frame ORF3a, has remained elusive. Herein, we show protein mitochondrial localization and alters metabolism, inducing shift from glucose to fatty acids oxidation enhanced oxidative...
OAS (2'-5'-oligoadenylate synthases) proteins and cyclic GMP-AMP synthase (cGAS, gene symbol: MB21D1) patrol the cytoplasm for presence of foreign nucleic acids. Upon binding to double-stranded RNA or DNA, cGAS produce nucleotide second messengers activate RNase L STING (stimulator interferon genes, TMEM173), respectively; this leads initiation antiviral responses. We analyzed evolutionary history MB21D1-TMEM173 OAS-RNASEL axes in primates bats found evidence widespread positive selection...
Abstract Analysis of the bat viruses most closely related to SARS‐CoV‐2 indicated that virus probably required limited adaptation spread in humans. Nonetheless, since its introduction human populations, must have been subject selective pressure imposed by immune system. We exploited availability a large number high‐quality genomes, as well validated epitope predictions, show B cell epitopes spike glycoprotein (S) and nucleocapsid protein (N) higher diversity than nonepitope positions....
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 primate-infecting cytomegaloviruses intra-species diversity clinical isolates provide genome-wide picture HCMV adaptation across different time-frames. During the human host, core viral genes...
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has triggered an unprecedented international effort to sequence complete viral genomes. We leveraged this wealth of information characterize the substitution spectrum SARS-CoV-2 and compare it with those other human animal coronaviruses. show that, once nucleotide composition is taken into account, most coronaviruses display a mutation dominated by C U G substitutions, feature that not shared positive-sense RNA...
AIM2 is a key cytoplasmatic pathogen-sensor that detects foreign DNA from viruses and bacteria; it can also recognize damaged or anomalous presence of DNA, promoting inflammasome assembly activation with the secretion IL-1β, thus sustaining chronic inflammatory state, potentially leading to onset autoinflammatory skin diseases. Given implication IL-1β pathway in pathogenesis syndromic hidradenitis suppurativa (HS), an immune-mediated condition, potential involvement was...
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 Africa Asia; New (NW) found Cricetidae Americas. We applied a selection-informed method to estimate that OW NW diverged less than ∼45,000 years ago (ya). By incorporating phylogeographic inference, we show emerged Latin America-Caribbean region ∼41,400-3,300 ya, whereas originated ∼23,100-1,880 most likely...
Abstract Herpes simplex virus types 1 and 2 (HSV-1 HSV-2) are ubiquitous human pathogens. Both viruses evolved from infecting African primates they thus thought to have left Africa during early migrations. We analyzed the population structure of HSV-1 HSV-2 circulating strains. Results indicated that populations limited geographic most evident clustering by geography is likely due recent bottlenecks. For HSV-2, only level accounted for so-called “worldwide” “African” lineages. Analysis...
Abstract The transcriptional repressor REST regulates many neuronal genes by binding RE1 motifs. About one third of human RE1s are recently evolved and specific to primates. As changes in the activity a transcription factor reverberate on its downstream targets, we assessed whether displays fast evolutionary rates We show that was targeted very strong positive selection during primate evolution. Positive also evident lineage, with six selected sites located region surrounds VNTR exon 4....
The endoplasmic reticulum enzyme glucose-6-phosphatase catalyzes the common terminal reaction in gluconeogenic/glycogenolytic pathways and plays a central role glucose homeostasis. In most mammals, different G6PC subunits are encoded by three paralogous genes (G6PC, G6PC2, G6PC3). Mutations G6PC3 responsible for human mendelian diseases, whereas variants G6PC2 associated with fasting (FG) levels.We analyzed evolutionary history of G6Pase genes. Results indicated that paralogs originated...
The protein product of the myxovirus resistance 2 (MX2) gene restricts HIV-1 and simian retroviruses. We demonstrate that MX2 evolved adaptively in mammals with distinct sites representing selection targets branches; mainly involved residues loop 4, previously shown to carry antiviral determinants. Modeling data indicated positively selected form a continuous surface on which folds into two antiparallel α-helices protruding from stalk domain. A population genetics–phylogenetics approach...
The complement system is an innate immunity effector mechanism; its action antagonized by a wide array of pathogens and evasion determines the virulence several infections. We investigated evolutionary history bacterial-encoded complement-interacting proteins. Complement components targeted evolved under strong selective pressure in primates, with selection acting on residues at contact interface microbial/viral Positively selected sites CFH C4BPA account for human specificity gonococcal...
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 1000 years ago. Hepaciviruses have been identified domestic wild mammals, largest viral diversity being observed bats rodents. The closest relatives of were found horses/donkeys (equine hepaciviruses, EHV). However, as human pathogen still an unsolved puzzle. Using...
Dietary shifts can drive molecular evolution in mammals and a major transition human history, the agricultural revolution, favored carbohydrate consumption. We investigated evolutionary history of nine genes encoding brush-border proteins involved digestion/absorption. Results indicated widespread adaptive mammals, with several branches experiencing episodic selection, particularly strong bats. Many positively selected sites map to functional protein regions (e.g., within glucosidase...
Varicella zoster virus (VZV) is the causative agent of chickenpox and shingles. The geographic distribution VZV clades was taken as evidence that migrated out Africa with human populations. We show extant strains most likely originated in Europe not Africa. also identified ancestral location for internal nodes phylogeny, including ancestor clade 5 strains. from 1, 2, 3, derived a major proportion their ancestry each 4 Conversely, viruses other displayed variable levels admixture. Some...
Filovirus infection is mediated by engagement of the surface-exposed glycoprotein (GP) its cellular receptor, NPC1 (Niemann-Pick C1). Two loops in C domain (NPC1-C) bind filovirus GP. Herein, we show that GP and NPC1-C evolve under mutual selective pressure. Analysis a large mammalian phylogeny indicated strong functional/structural constraints limit sequence space available for adaptive change most sites at contact interface with are negative selection. These notwithstanding, detected...
Centromeres have central functions in chromosome segregation, but centromeric DNA and centromere-binding proteins evolve rapidly most eukaryotes. The selective pressure(s) underlying the fast evolution of are presently unknown. An attractive possibility is that selfish centromeres promote their preferential inclusion oocyte to suppress meiotic drive (centromere hypothesis). We analysed patterns mammalian genes encode kinetochore microtubule (MT)-destabilizing factors. show several these at...
Abstract Plasmodium falciparum , the causative agent of deadliest form malaria, is a member Laverania subgenus, which includes ape‐infecting parasites. P. thought to have originated in gorillas, although infection now restricted humans. parasites display remarkable host‐specificity, partially mediated by interaction between parasite ligands and host receptors. We analyse evolution BSG (basigin) GYPA (glycophorin A) primates/hominins, as well their ‐encoded ligands, Pf RH 5 EBA 175. show...
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 longevity), suggesting differential selection depending on physiological characteristics. Telomeres, in analogy to centromeric regions, also represent candidate meiotic drivers subtelomeric DNA evolves rapidly. We analyzed evolutionary mammalian genes implicated homeostasis (TEL genes). detected widespread positive we tested...
A-to-I RNA editing operated by ADAR enzymes is extremely common in mammals. Several events coding regions have pivotal physiological roles and affect protein sequence (recoding events) or function. We analyzed the evolutionary history of 3 family genes their targets. Evolutionary analysis indicated that evolved adaptively primates, with strongest selection unique N-terminal domain interferon-inducible isoform. Positively selected residues human lineage were also detected deaminase binding...
Host genetic factors are thought to modulated the severity of disease caused by infection with 2009 H1N1 pandemic influenza virus (H1N1pdm09). The human CCR5 gene encodes a cytokine receptor important for cell-mediated immune response against H1N1pdm09. A 32-bp polymorphic deletion in coding sequence CCR5, so-called CCR5Δ32 allele, segregates populations European ancestry frequency 8-15%. high proportion heterozygotes was reported sample white Canadian critically-ill H1N1pdm09 infected...
Abstract The Old World ( OW ) arenavirus complex includes several species of rodent‐borne viruses, some which (i.e., Lassa virus, LASV and Lymphocytic choriomeningitis LCMV cause human diseases. Most infections are caused by rodent‐to‐human transmissions. Thus, viral evolution is largely determined events that occur in the wildlife reservoirs. We used a set human‐ rodent‐derived sequences to investigate evolutionary history underlying speciation, as well more recent selective accompanied...