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Human gammaherpesvirus 8 (HHV-8) consists of six major clades (A–F) based on the genetic sequence of the open reading frame (ORF)-K1. There are a few conflicting reports regarding the global distribution of the different HHV-8 genotypes. This study aimed to determine the global distribution of the different HHV-8 genotypes based on phylogenetic analysis of the ORF-K1 coding region using sequences published in the GenBank during 1997–2020 and construct a phylogenetic tree using the maximum likelihood algorithm with the GTR + I + G nucleotide substitution model. A total of 550 sequences from 38 countries/origins were analysed in this study. Genotypes A and C had similar global distributions and were prevalent in Africa and Europe. Genotype B was prevalent in Africa. Of the rare genotypes, genotype D was reported in East Asia and Oceania and genotype E in South America, while genotype F was prevalent in Africa. The highest genotypic diversity was reported in the American continent, with Brazil housing five HHV-8 genotypes (A, B, C, E, and F). In this study, we present update of the global distribution of HHV-8 genotypes, providing a basis for future epidemiological and evolutionary studies of HHV-8.

Ultraviolet radiation (UV) is causally linked to cutaneous melanoma, yet the underlying epigenetic mechanisms, known as molecular sensors of exposure, have not been characterized in clinical biospecimens. Here, we integrate clinical, epigenome (DNA methylome), genome and transcriptome profiling of 112 cutaneous melanoma from two multi-ethnic cohorts. We identify UV-related alterations in regulatory regions and immunological pathways, with multi-OMICs cancer driver potential affecting patient survival. TAPBP , the top gene, is critically involved in immune function and encompasses several UV-altered methylation sites that were validated by targeted sequencing, providing cost-effective opportunities for clinical application. The DNA methylome also reveals non UV-related aberrations underlying pathological differences between the cutaneous and 17 acral melanomas. Unsupervised epigenomic mapping demonstrated that non UV-mutant cutaneous melanoma more closely resembles acral rather than UV-exposed cutaneous melanoma, with the latter showing better patient prognosis than the other two forms. These gene-environment interactions reveal translationally impactful mechanisms in melanomagenesis. While cutaneous melanoma is linked to UV radiation, acral melanoma is not. Epigenetic mechanisms function as sensors to exposures and determinants of cell identity. Here, the authors use DNA methylation data to identify dysregulated pathways associated with UV radiation and pathobiology in cutaneous and acral melanomas.

Hepatitis B virus (HBV) genotype D (HBV/D) is globally widespread, and ten subgenotypes (D1 to D10) showing distinct geographic distributions have been described to date. The evolutionary history of HBV/D and its subgenotypes, for which few complete genome sequences are available, in the Americas is not well understood. The main objective of the current study was to determine the full-length genomic sequences of HBV/D isolates from Brazil and frequency, origin and spread of HBV/D subgenotypes in the Americas. Complete HBV/D genomes isolated from 39 Brazilian patients infected with subgenotypes D1 (n = 1), D2 (n = 10), D3 (n = 27), and D4 (n = 1) were sequenced and analyzed together with reference sequences using the Bayesian coalescent and phylogeographic framework. A search for HBV/D sequences available in GenBank revealed 209 complete and 926 partial genomes from American countries (Argentina, Brazil, Canada, Chile, Colombia, Cuba, Haiti, Martinique, Mexico, USA and Venezuela), with the major circulating subgenotypes identified as D1 (26%), D2 (17%), D3 (36%), D4 (21%), and D7 (1%) within the continent. The detailed evolutionary history of HBV/D in the Americas was investigated by using different evolutionary time scales. Spatiotemporal reconstruction analyses using short-term substitution rates suggested times of the most recent common ancestor for the American HBV/D subgenotypes coincident with mass migratory movements to Americas during the 19th and 20th centuries. In particular, significant linkages between Argentina and Syria (D1), Brazil and Central/Eastern Europe (D2), USA and India (D2), and Brazil and Southern Europe (D3) were estimated, consistent with historical and epidemiological data.

Several hepatitis B virus (HBV)-related factors, including the viral load, genotype, and genomic mutations, have been linked to the development of liver diseases. Therefore, in this study we aimed to investigate the influence of HBV genetic variability during acute and chronic infection phases. A real-time nested PCR was used to detect HBV DNA in all samples (acute, n = 22; chronic, n = 49). All samples were sequenced for phylogenetic and mutation analyses. Genotype A, sub-genotype A1, was the most common genotype in the study population. A total of 190 mutations were found in the pre-S/S gene area and the acute profile revealed a greater number of nucleotide mutations (p < 0.05). However, both profiles contained nucleotide mutations linked to immune escape and an increased risk of hepatocellular carcinomas (acute, A7T; chronic, A7Q). Furthermore, 17 amino acid substitutions were identified in the viral polymerase region, including the drug resistance mutations lamivudine and entecavir (rtL180M), with statistically significant differences between the mutant and wild type strains. Owing to the natural occurrence of these mutations, it is important to screen for resistance mutations before beginning therapy.

The hepatitis C virus (HCV) has remarkable genetic diversity and exists as eight genotypes (1 to 8) with distinct geographic distributions. No complete genome sequence of HCV subtype 2b (HCV-2b) is available from Latin American countries, and the factors underlying its emergence and spread within the continent remain unknown. The present study was conducted to determine the first full-length genomic sequences of HCV-2b isolates from Latin America and reconstruct the spatial and temporal diversification of this subtype in Brazil. Nearly complete HCV-2b genomes isolated from two Brazilian patients were obtained by direct sequencing of long PCR fragments and analyzed together with reference sequences using the Bayesian coalescent and phylogeographic framework approaches. The two HCV-2b genomes were 9318 nucleotides (nt) in length (nt 37–9354). Interestingly, the long RT-PCR technique was able to detect co-circulation of viral variants that contained an in-frame deletion of 2022 nt encompassing E1, E2, and p7 proteins. Spatiotemporal reconstruction analyses suggest that HCV-2b had a single introduction in Brazil during the early 1980s, displaying an epidemic history characterized by a low and virtually constant population size until the present time. These results coincide with epidemiological data in Brazil and may explain the low national prevalence of this subtype.

Hepatitis B virus (HBV) diversity has not been previously studied in Cape Verde. The archipelago was discovered in 1460 by Portuguese explorers, who brought African slaves to colonise the islands. In this study, we investigated the HBV characteristics from 183 HBsAg-positive Cape Verdean individuals. Phylogenetic analysis of the pre-S/S region and the full-length genomes revealed 54 isolates with HBV/A1 (57%), 21 with HBV/A2 (22%), 19 with HBV/E (20%), and one with HBV/D (1%). HBV genotypes and subgenotypes were unequally distributed through the islands. In São Vicente, the main northern island, most isolates (84%) belonged to the African-originated HBV/A1, with the remaining isolates belonging to HBV/A2, which is prevalent in Europe. Interestingly, the HBV/A1 isolates from São Vicente were closely related to Brazilian sequences into the Asian-American clade, which suggests the dissemination of common African ancestors through slave trade. In contrast, in Santiago and nearby southern islands, where a recent influx from different populations circulates, a higher diversity of HBV was observed: HBV/A1 (40%); HBV/E (32%); HBV/A2 (28%); and HBV/D (1%). HBV/E is a recent genotype disseminated in Africa that was absent in the era of the slave trade. African and European human flows at different times of the history may explain the HBV diversity in Cape Verde. The possible origin and specifics of each HBV genotype circulating in Cape Verde are discussed.

Men who have sex with men (MSM) are at increased risk of exposure to hepatitis B virus (HBV) compared with the general population. This study aims to assess the epidemiological and virological characteristics of HBV infection in a sample of MSM in Brazil, where data are scarce. A cross-sectional study was conducted among MSM in the City of Goiânia, Central Brazil, from March to November 2014, using Respondent-Driven Sampling (RDS). After signing the consent form, participants were interviewed and a blood sample collected. All samples were tested for HBV serological markers and HBV DNA. HBV nucleotide sequence analysis was also performed. A total of 522 MSM were recruited in the study. The prevalence of HBV infection (current or past [presence of anti-HBc marker]) was 15.4% (95% CI: 8.7-25.8) and the rate of HBsAg carriers was 0.6% (95% CI: 0.2-1.6). About 40% (95% CI: 32.3-48.8) of the participants had serological evidence of previous HBV vaccination (reactive for isolated anti-HBs). In addition, 44.3% (95% CI: 36.1-52.9) were seronegative for all HBV markers. Age over 25 years old, receptive anal intercourse, previous sex with women, and history of sexually transmitted infections (STIs) were factors associated with HBV infection. HBV DNA was detected only in HBsAg-positive individuals. HBV isolates were classified into genotype A (subgenotypes A1 and A2), and some mutations were identified throughout the genome. Therefore, occult HBV infection was not observed in the study population. Public health strategies should be improved for the MSM population in order to prevent HBV and other STIs, as well as to provide appropriate management of patients with active infections.

Background Cancer is the leading cause of disease-related mortality in children. Causes of leukemia, the most common form, are largely unknown. Growing evidence points to an origin in-utero , when global redistribution of DNA methylation occurs driving tissue differentiation. Methods Epigenome-wide DNA methylation was profiled in surrogate (blood) and target (bone marrow) tissues at birth, diagnosis, remission and relapse of pediatric pre-B acute lymphoblastic leukemia (pre-B ALL) patients. Double-blinded analyses was performed between prospective cohorts extending from birth to diagnosis and retrospective studies backtracking from clinical disease to birth. Validation was carried out using independent technologies and populations. Results The imprinted and immuno-modulating VTRNA2-1 was hypermethylated (FDR<0.05) at birth in nested cases relative to controls in all tested populations (totaling 317 cases and 483 controls), including European and Hispanic ancestries. VTRNA2-1 methylation was stable over follow-up years after birth and across surrogate, target and other tissues ( n =5,023 tissues; 30 types). When profiled in leukemic tissues from two clinical cohorts (totaling 644 cases), VTRNA2-1 methylation exhibited higher levels at diagnosis relative to controls, it reset back to normal levels at remission, and then re-increased to above control levels at relapse. Hypermethylation was significantly associated with worse pre-B ALL patient survival and with reduced VTRNA2-1 expression ( n =2,294 tissues; 26 types), supporting a functional and translational role for VTRNA2-1 methylation. Conclusion This study provides proof-of-concept to detect at birth epigenetic precursors of pediatric pre-B ALL. These alterations were reproducible with different technologies, in three continents and in two ethnicities, and can offer biomarkers for early detection and prognosis as well as actionable targets for therapy. Key points • Precursors of pediatric acute lymphoblastic leukemia may be of epigenetic origin, detectable since birth and affecting patient prognosis. • These epigenetic precursors can be robust over several years and across several populations, ethnicities and surrogate and target tissues.

Occult hepatitis B virus infection (OBI) is one of the most challenging entities in the field of viral hepatitis. The virological and clinical relevance of OBI in patients treated with novel direct-acting antivirals (DAA) for hepatitis C virus (HCV) infections is currently a topic of hot debate. In cases where hepatitis B surface antigen (HBsAg) is not detected, DAA treatment is often initiated without examining for the presence of hepatitis B virus (HBV) DNA. In this study, the incidence of OBI was investigated in 114 HCV patients prior to application of DAAs who did not respond to pegylated interferon and ribavirin (PEG-INF and RBV) treatment. Serum samples were screened for HBV serological markers (antibody to hepatitis B core antigen [anti-HBc] and HBsAg). Samples positive for anti-HBc without HBsAg were further examined via real-time PCR (qPCR), nested PCR and S-gene mutational analyses. Overall, anti-HBc was detected in 37.7% chronic HCV patients and 2.6% had OBI with a baseline HBV DNA viral load < 2000 IU/mL before DAA therapy. One patient was identified as HBV genotype A1 without mutations in surface protein. Our collective data highlight the importance of clinicians being aware of potential anti-HBc positivity in patients with hepatitis C and the issues surrounding OBI screening before initiation of treatment with novel DAAs.

Hepatitis B virus (HBV) has been classified into 10 distinct serological subtypes of the surface antigen (HBsAg) that can be predicted by sequencing of the corresponding S gene. HBV genotype D usually displays determinants of subtypes ayw2 or ayw3. On the other hand, subtype adrq+ has been found exclusively in association with genotype C. Here, we describe the first HBV genome (isolate BR32) belonging to genotype D with the serological subtype adrq+. This isolate had a genome length of 3,062 nucleotides (nt), and no recombination events were observed in the BR32 genome that could explain the occurrence of the subtype adr in a genotype D isolate. Analysis of the quasispecies population revealed that 28 out of 30 clones (93%) were of subtype adrq+, while the subtypes of the two remaining could not be determined, since they contained an S residue (instead of K or R) at position 122 of HBsAg. These results will contribute to further epidemiological and evolutionary studies of HBV.