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1.
BMC Bioinformatics ; 25(1): 125, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38519883

RESUMO

In the battle of the host against lentiviral pathogenesis, the immune response is crucial. However, several questions remain unanswered about the interaction with different viruses and their influence on disease progression. The simian immunodeficiency virus (SIV) infecting nonhuman primates (NHP) is widely used as a model for the study of the human immunodeficiency virus (HIV) both because they are evolutionarily linked and because they share physiological and anatomical similarities that are largely explored to understand the disease progression. The HIHISIV database was developed to support researchers to integrate and evaluate the large number of transcriptional data associated with the presence/absence of the pathogen (SIV or HIV) and the host response (NHP and human). The datasets are composed of microarray and RNA-Seq gene expression data that were selected, curated, analyzed, enriched, and stored in a relational database. Six query templates comprise the main data analysis functions and the resulting information can be downloaded. The HIHISIV database, available at  https://hihisiv.github.io , provides accurate resources for browsing and visualizing results and for more robust analyses of pre-existing data in transcriptome repositories.


Assuntos
Infecções por HIV , Síndrome de Imunodeficiência Adquirida dos Símios , Vírus da Imunodeficiência Símia , Animais , Humanos , Vírus da Imunodeficiência Símia/genética , HIV , Síndrome de Imunodeficiência Adquirida dos Símios/genética , Progressão da Doença , Imunidade , Expressão Gênica
2.
Heliyon ; 10(3): e25474, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38327440

RESUMO

Since human papillomavirus (HPV) is recognized as the causative agent of cervical cancer and associated with anogenital non-cervical and oropharyngeal cancers, the characterization of the HPV types circulating in different geographic regions is an important tool in screening and prevention. In this context, this study compared four methodologies for HPV detection and genotyping: real-time PCR (Cobas® HPV test), nested PCR followed by conventional Sanger sequencing, reverse hybridization (High + Low PapillomaStrip® kit) and next-generation sequencing (NGS) at an Illumina HiSeq2500 platform. Cervical samples from patients followed at the Family Health Strategy from Juiz de Fora, Minas Gerais, Brazil, were collected and subjected to the real-time PCR. Of those, 114 were included in this study according to the results obtained with the real-time PCR, considered herein as the gold standard method. For the 110 samples tested by at least one methodology in addition to real-time PCR, NGS showed the lowest concordance rates of HPV and high-risk HPV identification compared to the other three methods (67-75 %). Real-time PCR and Sanger sequencing showed the highest rates of concordance (97-100 %). All methods differed in their sensitivity and specificity. HPV genotyping contributes to individual risk stratification, therapeutic decisions, epidemiological studies and vaccine development, supporting approaches in prevention, healthcare and management of HPV infection.

3.
PLoS Pathog ; 19(12): e1011860, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38064524

RESUMO

The CD4 receptor, by stabilizing TCR-MHC II interactions, plays a central role in adaptive immunity. It also serves as the HIV docking receptor. The HIV gp120 envelope protein binds directly to CD4. This interaction is a prerequisite for viral entry. gp120 also binds to ⍺4ß7, an integrin that is expressed on a subset of memory CD4+ T cells. HIV tropisms for CD4+ T cells and gut tissues are central features of HIV pathogenesis. We report that CD4 binds directly to ⍺4ß7 in a dynamic way, consistent with a cis regulatory interaction. The molecular details of this interaction are related to the way in which gp120 interacts with both receptors. Like MAdCAM-1 and VCAM-1, two recognized ligands of ⍺4ß7, the binding interface on CD4 includes 2 sites (1° and accessory), distributed across its two N-terminal IgSF domains (D1 and D2). The 1° site includes a sequence in the G ß-strand of CD4 D2, KIDIV, that binds directly to ⍺4ß7. This pentapeptide sequence occurs infrequently in eukaryotic proteins. However, a closely related and conserved sequence, KLDIV, appears in the V2 domain of gp120. KLDIV mediates gp120-⍺4ß7 binding. The accessory ⍺4ß7 binding site on CD4 includes Phe43. The Phe43 aromatic ring protrudes outward from one edge of a loop connecting the C'C" strands of CD4 D1. Phe43 is a principal contact for HIV gp120. It interacts with conserved residues in the recessed CD4 binding pocket. Substitution of Phe43 abrogates CD4 binding to both gp120 and ⍺4ß7. As such, the interactions of gp120 with both CD4 and ⍺4ß7 reflect elements of their interactions with each other. These findings indicate that gp120 specificities for CD4 and ⍺4ß7 are interrelated and suggest that selective pressures which produced a CD4 tropic virus that replicates in gut tissues are linked to a dynamic interaction between these two receptors.


Assuntos
Infecções por HIV , Integrinas , Humanos , Integrinas/metabolismo , Sítios de Ligação , Antígenos CD4 , Linfócitos T CD4-Positivos/metabolismo , Proteína gp120 do Envelope de HIV/metabolismo
4.
Genet Mol Biol ; 46(4): e20230015, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38051353

RESUMO

A complete genome of the first anellovirus infecting the wild felid Leopardus pardalis (ocelot) and a partial genome were assembled and annotated through high-throughput sequencing protocols followed by Sanger sequencing validation. The full-length virus obtained comprises 2,003 bp, while the partial genome comprises 1,224 bp. Phylogenetic analysis grouped these two sequences in two distinct clusters related to previously described Felidae anelloviruses. The ORF1 of the partial genome was identified as a new species provisionally called Torque teno ocelot virus, with 53.6% identity with its sister lineage. The complete genome was inferred as a new representative of the Torque teno felid virus 3 species, with 73.28% identity to the closest reference. This study expands known virus diversity and the host span of anelloviruses.

5.
J Reprod Immunol ; 159: 104134, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37634319

RESUMO

The Human Leukocyte Antigen G (HLA-G) is an immunoregulatory molecule with a critical role in pregnancy success. HLA-G alleles are associated with differential susceptibility to multiple conditions, including gestational problems, infectious diseases, and viral persistence. Of note, both herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) can impair HLA-G expression, interfering with HLA-G-associated immunoregulation. On the other hand, the impacts of HLA-G alleles on susceptibility to Herpesviridae infection is a neglected issue. Therefore, this study evaluated HLA-G allele frequencies and their associations with placental Herpesviridae infection in women from southern Brazil. Placenta samples were collected soon after delivery, and detection of viral DNA of HSV-1, HSV-2 and human cytomegalovirus (HCMV) was performed by polymerase chain reaction (PCR). A fragment of HLA-G (exons 2-4) was amplified by PCR, sequenced, and analyzed to allele determination. One hundred and seventy women had their alleles determined. Overall, 25 HLA-G alleles were found, distributed into 56 different genotypes. The most frequent alleles were G* 01:01:01 and G* 01:01:02, found in 37.9 % and 16.5 % of samples, respectively. Among the 170 women, 89 (52.4 %) tested positive for Herpesviridae DNA in the placenta, 55 (32.3 %) tested negative, 3 (1.8 %) were negative for HSV-1 and HSV-2 (with absent HCMV data), and 23 (13.5 %) were undetermined. The G* 01:01:01 allele was significantly associated with an increased risk of placental HSV-1 infection (p = 0.0151; OR=1.837; IC=1.108-3.045). This study describes new information concerning placental HLA-G alleles in women from southern Brazil and helps explain how genetic background can modify susceptibility to placental infections.


Assuntos
Herpes Simples , Herpesvirus Humano 1 , Gravidez , Feminino , Humanos , Herpesvirus Humano 1/genética , Alelos , Antígenos HLA-G/genética , Brasil/epidemiologia , Placenta , Herpesvirus Humano 2/genética , Citomegalovirus
6.
AIDS ; 37(15): 2331-2338, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37650761

RESUMO

OBJECTIVE: Combinatorial antiretroviral therapy provided improvement of HIV patients' immune function and a decrease in the incidence of non-Hodgkin lymphoma (NHL). Diffuse large B-cell lymphoma (DLBCL) is one of the most common NHL forms affecting HIV+ patients. The present study aimed to evaluate the impact of HIV infection on the prognosis of patients treated for DLBCL in a reference cancer treatment center in Brazil. METHODS: A retrospective case-control study was developed with patients followed-up at the Brazilian National Cancer Institute, in which 243 DLBCL patients (91 HIV+ and 152 HIV-) were enrolled. HIV- controls were matched to HIV+ according to date of cancer diagnosis, clinical staging, primary cancer treatment and date of birth. Sociodemographic and cancer treatment data were extracted from medical charts. Kaplan-Meier analyses were carried out to estimate survival, while univariate and multiple Cox regression analyses were used to determine factors associated with mortality. RESULTS: A total of 98 deaths were observed in a 5-year period after cancer diagnosis. A negative association of HIV infection with both overall and disease-specific survival 1 year after cancer diagnosis was observed [hazard ratio (HR) = 1.98 and 1.96, respectively]. The negative association with HIV infection with disease-specific survival remained significant for a 5-year period after cancer diagnosis (HR = 1.53). HIV viral load above 1000 copies/ml at study entry was also associated with shorter overall and cancer-specific survival. CONCLUSIONS: HIV infection negatively impacted prognosis and mortality of DLBCL patients irrespective of cancer-related clinical factors.


Assuntos
Infecções por HIV , Linfoma Difuso de Grandes Células B , Linfoma não Hodgkin , Humanos , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Brasil/epidemiologia , Estudos Retrospectivos , Estudos de Casos e Controles , Linfoma Difuso de Grandes Células B/complicações , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Prognóstico
7.
Front Immunol ; 14: 1147950, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37180114

RESUMO

The relationship among microbiome, immunity and cervical cancer has been targeted by several studies, yet many questions remain unanswered. We characterized herein the virome and bacteriome from cervical samples and correlated these findings with innate immunity gene expression in a Brazilian convenience sample of HPV-infected (HPV+) and uninfected (HPV-) women. For this purpose, innate immune gene expression data were correlated to metagenomic information. Correlation analysis showed that interferon (IFN) is able to differentially modulate pattern recognition receptors (PRRs) expression based on HPV status. Virome analysis indicated that HPV infection correlates to the presence of Anellovirus (AV) and seven complete HPV genomes were assembled. Bacteriome results unveiled that vaginal community state types (CST) distribution was independent of HPV or AV status, although bacterial phyla distribution differed between groups. Furthermore, TLR3 and IFNαR2 levels were higher in the Lactobacillus no iners-dominated mucosa and we detected correlations among RIG-like receptors (RLR) associated genes and abundance of specific anaerobic bacteria. Collectively, our data show an intriguing connection between HPV and AV infections that could foster cervical cancer development. Besides that, TLR3 and IFNαR2 seem to create a protective milieu in healthy cervical mucosa (L. no iners-dominated), and RLRs, known to recognize viral RNA, were correlated to anaerobic bacteria suggesting that they might be related to dysbiosis.


Assuntos
Microbiota , Infecções por Papillomavirus , Neoplasias do Colo do Útero , Feminino , Humanos , Colo do Útero , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/metabolismo , Brasil , Receptor 3 Toll-Like/genética , Bactérias/genética , Expressão Gênica
8.
J Antimicrob Chemother ; 78(6): 1444-1453, 2023 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-37039023

RESUMO

BACKGROUND: Antiretroviral therapy has revolutionized HIV treatment, increasing quality and life expectancy of people living with HIV (PLWH). However, the expansion of treatment has resulted in an increase in antiretroviral-resistant viruses, which can be an obstacle to maintenance of successful ART. OBJECTIVES: This study analysed the genetic composition of the HIV near full-length genome (NFLG) from archived proviruses of PLWH under successful ART, and determined the presence/frequency of drug resistance mutations (DRMs) and viral subtype. PATIENTS AND METHODS: Forty-six PLWH from Rio de Janeiro (RJ) and 40 from Rio Grande (RS) had proviral HIV NFLG PCR-amplified and ultradeep sequenced. The presence/frequency of DRMs were analysed in Geneious. Phylogenetic analyses were performed using PhyML and SimPlot. RESULTS: All samples included in the study were sequenced and 69 (80.2%) had the HIV NFLG determined. RJ and RS showed a predominance of HIV subtypes B (78.3%) and C (67.5%), respectively. Overall, 168 DRMs were found in 63 (73.3%) samples, and 105 (62.5%) of them were minority variants. Among DRMs, 41 (39.0%) minority variants and 33 (52.4%) variants with frequency above 20.0% in the viral population were able to confer some degree of resistance to at least one drug in use by respective patients, yet no one showed signs of therapeutic failure. CONCLUSIONS: Our study contributes to the understanding of the impact of DRMs on successful therapy and supports the sustainability of combinatorial ART, because all patients maintained their successful treatment despite the high prevalence of DRMs at low (62.5%) or high (37.5%) frequency.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Soropositividade para HIV , HIV-1 , Humanos , HIV-1/genética , Filogenia , Brasil/epidemiologia , Antirretrovirais/farmacologia , Antirretrovirais/uso terapêutico , Soropositividade para HIV/tratamento farmacológico , Mutação , Provírus/genética , Farmacorresistência Viral/genética , Genótipo , Fármacos Anti-HIV/farmacologia , Fármacos Anti-HIV/uso terapêutico
9.
PLoS Pathog ; 19(3): e1011209, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36897929

RESUMO

CD4+ tissue resident memory T cells (TRMs) are implicated in the formation of persistent HIV reservoirs that are established during the very early stages of infection. The tissue-specific factors that direct T cells to establish tissue residency are not well defined, nor are the factors that establish viral latency. We report that costimulation via MAdCAM-1 and retinoic acid (RA), two constituents of gut tissues, together with TGF-ß, promote the differentiation of CD4+ T cells into a distinct subset α4ß7+CD69+CD103+ TRM-like cells. Among the costimulatory ligands we evaluated, MAdCAM-1 was unique in its capacity to upregulate both CCR5 and CCR9. MAdCAM-1 costimulation rendered cells susceptible to HIV infection. Differentiation of TRM-like cells was reduced by MAdCAM-1 antagonists developed to treat inflammatory bowel diseases. These finding provide a framework to better understand the contribution of CD4+ TRMs to persistent viral reservoirs and HIV pathogenesis.


Assuntos
Linfócitos T CD4-Positivos , Infecções por HIV , Humanos , Fator de Crescimento Transformador beta , Tretinoína/farmacologia , Diferenciação Celular , Memória Imunológica , Receptores CCR5
10.
Viruses ; 14(12)2022 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-36560657

RESUMO

The APOBEC3 (A3) proteins are cytidine deaminases that exhibit the ability to insert mutations in DNA and/or RNA sequences. APOBEC3B (A3B) has been evidenced as a DNA mutagen with consistent high expression in several cancer types. Data concerning the A3B influence on HPV infection and cervical cancer are limited and controversial. We investigated the role of A3B expression levels in cervical cancer in affected women positive for infection by different HPV types. Tumor biopsies from cancerous uterine cervix were collected from 216 women registered at Hospital do Câncer II of Instituto Nacional de Câncer, and infecting HPV was typed. A3B expression levels were quantified from RNA samples extracted from cervical biopsies using real-time quantitative PCR. Median A3B expression levels were higher among HPV18+ samples when compared to HPV16+ counterparts and were also increased compared to samples positive for other HPV types. In squamous cell carcinoma, HPV18+ samples also showed increased median A3B expression when compared to HPV Alpha-9 species or only to HPV16+ samples. Our findings suggest that A3B expression is differentially upregulated in cervical cancer samples infected with HPV18. A3B could be potentially used as a biomarker for HPV infection and as a prognostic tool for clinical outcomes in the context of cervical cancer.


Assuntos
Citidina Desaminase , Infecções por Papillomavirus , Neoplasias do Colo do Útero , Feminino , Humanos , Citidina Desaminase/genética , DNA , Papillomavirus Humano 18 , Antígenos de Histocompatibilidade Menor/genética , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/genética , RNA Mensageiro/genética , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/virologia
11.
Front Med (Lausanne) ; 9: 945621, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36091685

RESUMO

As a middle-income country, Brazil has one of the largest public health systems worldwide, which deals with free and universal access to health care. Regarding cervical cancer, the country possesses a large infrastructure for the screening of premalignant and malignant lesions, but yet based on old technology, having Papanicolaou as the major screening method, followed by colposcopy and treatment. Also, large disparities in access are present, which makes effectiveness of screening and treatment in different regions of the country highly unequal. In this review, we describe and evaluate the current screening, treatment and prophylactic (HPV vaccination) strategies to combat cervical cancer in Brazil, and discuss potential incorporation of more recent technologies in these areas in the country to pave its way toward cervical cancer elimination.

12.
Viruses ; 14(8)2022 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-36016402

RESUMO

Rituximab promotes strong immunosuppression leading to a high risk of hepatitis B reactivation (HBV-R) and chronic infection. Current recommendations on HBV-R prevention are expensive and poorly individualized. In resolved hepatitis B patients, previous studies suggest that anti-HBs titers before immunosuppression can predict HBV-R risk. However, guidelines claim that additional data are necessary before recommending spare drug prophylaxis in patients with high anti-HBs titers. On the other hand, in patients with no previous contact with HBV, guidelines recommend vaccine before immunosuppression despite minimal evidence available. To shed light on these knowledge gaps, two prospective studies were conducted to evaluate anti-HBs in hematological cancer patients treated with rituximab. In the first study, anti-HBs-positive patients were referred for following up antibody titers before and during immunosuppression. Patients with anti-HBs ≥ 100 mIU/mL before immunosuppression had no negative seroconversion (anti-HBs loss), in contrast to 18% of those with anti-HBs < 100 mIU/mL. In the second study, patients with no previous contact with HBV were invited to receive HBV vaccine before rituximab chemotherapy. None seroconverted with anti-HBs. In conclusion, both studies reinforce the need to review concepts about HBV prevention during immunosuppression on current guidelines. Narrowing the use of drug prophylaxis and improving vaccine indications are recommended.


Assuntos
Vacinas contra Hepatite B , Hepatite B , DNA Viral , Anticorpos Anti-Hepatite B , Antígenos de Superfície da Hepatite B , Vírus da Hepatite B/genética , Humanos , Terapia de Imunossupressão , Estudos Prospectivos , Rituximab/uso terapêutico , Ativação Viral
13.
Breast ; 65: 151-156, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35970029

RESUMO

BACKGROUND: The goal was to assess the survival of HIV+ women and HIV- women for breast cancer at a referral center for cancer treatment in Brazil. METHODS: A retrospective cohort study was performed. A total of 136 women patients with breast cancer were included, being 36 HIV+ women and 100 HIV- women. Controls (HIV-) were selected according to HIV status, matched by date of cancer diagnosis, clinical stage, breast cancer treatment, and date of birth. Sociodemographic and cancer treatment data, as well as clinical HIV data, were extracted from physical and electronic medical records and secondary Instituto Nacional of cancer databases. To estimate survival, the Kaplan-Meier method was used. To determine the factors associated with mortality, Cox regression were used. RESULTS: The mean age of patients at diagnosis of cancer was 52 years. Regarding marital status, HIV+ patients had a higher frequency of single status). There were 44.1% deaths that occurred during the study period. Among HIV+ patients, there were 16 deaths, 15 of which were due to cancer. In HIV- patients there were 44 deaths (44%), with 32 cancer as the cause of death and 12 due to other causes. For the analysis of Overall. Differences were found in overall survival at 60 months (p=0.026), 55% and 69% respectively. The increased risk of death at 60 months among HIV+ women was observed also, after adjusting for schooling and molecular subtype (HR=1.95; 95% CI 1.03 - 3.70; p=0.041). CONCLUSION: HIV infection influenced a worse prognosis for women with breast cancer regardless of tumor factors.


Assuntos
Neoplasias da Mama , Infecções por HIV , Brasil/epidemiologia , Neoplasias da Mama/complicações , Neoplasias da Mama/terapia , Estudos de Coortes , Feminino , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Humanos , Pessoa de Meia-Idade , National Cancer Institute (U.S.) , Estudos Retrospectivos , Estados Unidos
14.
Front Microbiol ; 13: 946549, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35958144

RESUMO

Chronically immunosuppressed patients infected with SARS-CoV-2 often experience prolonged virus shedding, and may pave the way to the emergence of mutations that render viral variants of concern (VOC) able to escape immune responses induced by natural infection or by vaccination. We report herein a SARS-CoV-2+ cancer patient from the beginning of the COVID-19 pandemic whose virus quasispecies across multiple timepoints carried several immune escape mutations found in more contemporary VOC, such as alpha, delta and omicron, that appeared to be selected for during infection. We hypothesize that immunosuppressed patients may represent the source of VOC seen throughout the COVID-19 pandemics.

15.
Viruses ; 14(7)2022 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-35891551

RESUMO

Many drugs have been evaluated to reactivate HIV-1 from cellular reservoirs, but the off-target effects of these latency reversal agents (LRA) remain poorly defined. Transposable elements (TEs) are reactivated during HIV-1 infection, but studies of potential off-target drug effects on TE expression have been limited. We analyzed the differential expression of TEs induced by canonical and non-canonical NF-κB signaling. We evaluated the effect of PKC agonists (Bryostatin and Ingenol B) on the expression of TEs in memory CD4+ T cells. Ingenol B induced 38 differentially expressed TEs (17 HERV (45%) and 21 L1 (55%)). Interestingly, TE expression in effector memory CD4+ T cells was more affected by Bryostatin compared to other memory T-cell subsets, with 121 (107 upregulated and 14 downregulated) differentially expressed (DE) TEs. Of these, 31% (n = 37) were HERVs, and 69% (n = 84) were LINE-1 (L1). AZD5582 induced 753 DE TEs (406 HERV (54%) and 347 L1 (46%)). Together, our findings show that canonical and non-canonical NF-κB signaling activation leads to retroelement expressions as an off-target effect. Furthermore, our data highlights the importance of exploring the interaction between LRAs and the expression of retroelements in the context of HIV-1 eradication strategies.


Assuntos
Elementos de DNA Transponíveis , Infecções por HIV , Soropositividade para HIV , NF-kappa B , Latência Viral , Briostatinas/farmacologia , Linfócitos T CD4-Positivos/metabolismo , Diterpenos/farmacologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/metabolismo , HIV-1 , Humanos , NF-kappa B/metabolismo , Ativação Viral
16.
Front Microbiol ; 13: 1074382, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36713167

RESUMO

Due to immunosuppressive cancer therapies, cancer patients diagnosed with COVID-19 have a higher chance of developing severe symptoms and present a higher mortality rate in comparison to the general population. Here we show a comparative analysis of the microbiome from naso-oropharyngeal samples of breast cancer patients with respect to SARS-CoV-2 status and identified bacteria associated with symptom severity. Total DNA of naso-oropharyngeal swabs from 74 women with or without breast cancer, positive or negative for SARS-CoV-2 were PCR-amplified for 16S-rDNA V3 and V4 regions and submitted to massive parallel sequencing. Sequencing data were analyzed with QIIME2 and taxonomic identification was performed using the q2-feature-classifier QIIME2 plugin, the Greengenes Database, and amplicon sequence variants (ASV) analysis. A total of 486 different bacteria were identified. No difference was found in taxa diversity between sample groups. Cluster analysis did not group the samples concerning SARS-CoV-2 status, breast cancer diagnosis, or symptom severity. Three taxa (Pseudomonas, Moraxella, and Klebsiella,) showed to be overrepresented in women with breast cancer and positive for SARS-CoV-2 when compared to the other women groups, and five bacterial groups were associated with COVID-19 severity among breast cancer patients: Staphylococcus, Staphylococcus epidermidis, Scardovia, Parasegitibacter luogiensis, and Thermomonas. The presence of Staphylococcus in COVID-19 breast cancer patients may possibly be a consequence of nosocomial infection.

17.
Infect Genet Evol ; 94: 104998, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34252616

RESUMO

After a one-year rollout of the pandemic caused by SARS-CoV-2, the continuous dissemination of the virus has generated a number of variants with increased transmissibility and infectivity, called variants of concern (VOC), which now predominate worldwide. Concerns about the susceptibility of humans that have already been infected before or those already vaccinated to infection by VOC rise among scientists and clinicians. Herein, we assessed the prevalence of different VOC among recent infections at the Brazilian National Cancer Institute (Rio de Janeiro, Brazil). By using a Sanger-based sequencing approach targeting the viral S gene to identify VOC, we have analyzed 72 recent infections. The overall prevalence of VOC was 97%. Among the subjects analyzed, six had been vaccinated with the ChAdOx1-S/nCoV-19 (n = 4; one with two doses and three with one dose) or the CoronaVac (n = 2; both with 2 doses) vaccine, while five subjects represented reinfection cases, being two of them also part of the vaccinated group (each one with one vaccine type). All vaccinated and re-infected subjects carried VOC irrespective of the vaccine type taken, the number of doses taken, IgG titers or being previously infected during the first wave of the Brazilian pandemic. Importantly, all six vaccinees only had mild symptoms. We present here several examples of how natural infections or vaccination may not be fully capable of conferring sterilizing immunity against VOC.


Assuntos
Vacinas contra COVID-19/administração & dosagem , COVID-19/imunologia , COVID-19/virologia , SARS-CoV-2/isolamento & purificação , Glicoproteína da Espícula de Coronavírus/genética , Brasil/epidemiologia , COVID-19/diagnóstico , COVID-19/epidemiologia , Humanos , Pandemias , Filogenia , SARS-CoV-2/classificação , SARS-CoV-2/genética , Vacinação
18.
Cancers (Basel) ; 13(14)2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34298727

RESUMO

Retroelements are expressed in diverse types of cancer and are related to tumorigenesis and to cancer progression. We characterized the expression of retroelements in cervical cancer and explored their interplay with HPV infection and their association with expression of neighboring genes. Forty biopsies of invasive cervical carcinoma (squamous cell carcinomas and adenocarcinomas) with genotyped HPV were selected and analyzed for human endogenous retrovirus (HERV) and long interspersed nuclear element 1 (L1) expression through RNA-seq data. We found 8060 retroelements expressed in the samples and a negative correlation of DNA methyltransferase 1 expression with the two most expressed L1 elements. A total of 103 retroelements were found differentially expressed between tumor histological types and between HPV types, including several HERV families (HERV-K, HERV-H, HERV-E, HERV-I and HERV-L). The comparison between HPV mono- and co-infections showed the highest proportion of differentially expressed L1 elements. The location of retroelements affected neighboring gene expression, such as shown for the interleukin-20 gene family. Three HERVs and seven L1 were located close to this gene family and two L1 showed a positive association with IL20RB expression. This study describes the expression of retroelements in cervical cancer and shows their association with HPV status and host gene expression.

19.
Front Oncol ; 11: 675353, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33996608

RESUMO

Non-Hodgkin lymphoma is the most common malignancy affecting people living with HIV (PLWH). Among its several subtypes, diffuse large B-cell lymphoma (DLBCL) is an important manifestation within the HIV-infected compartment of the population. Since HIV is able to modulate B cells and promote lymphomagenesis through direct and indirect mechanisms, HIV-related DLBCL has specific characteristics. In this review, we address the clinical and molecular properties of DLBCL disease in the context of HIV infection, as well as the mechanisms by which HIV is able to modulate B lymphocytes and induce their transformation into lymphoma.

20.
Virus Evol ; 7(1): veab013, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33738124

RESUMO

Numerous factors have been identified to influence susceptibility to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and disease severity. Cancer patients are more prone to clinically evolve to more severe COVID-19 conditions, but the determinants of such a more severe outcome remain largely unknown. We have determined the full-length SARS-CoV-2 genomic sequences of cancer patients and healthcare workers (non-cancer controls) by deep sequencing and investigated the within-host viral population of each infection, quantifying intrahost genetic diversity. Naso- and oropharyngeal SARS-CoV-2+ swabs from 57 cancer patients and 14 healthcare workers from the Brazilian National Cancer Institute were collected in April to May 2020. Complete genome amplification using ARTIC network V3 multiplex primers was performed followed by next-generation sequencing. Assemblies were conducted in Geneious R11, where consensus sequences were extracted and intrahost single nucleotide variants were identified. Maximum likelihood phylogenetic analysis was performed using PhyMLv.3.0 and lineages were classified using Pangolin and CoV-GLUE. Phylogenetic analysis showed that all but one strain belonged to clade B1.1. Four genetically linked mutations known as the globally dominant SARS-CoV-2 haplotype (C241T, C3037T, C14408T and A23403G) were found in the majority of consensus sequences. SNV signatures of previously characterized Brazilian genomes were also observed in most samples. Another 85 SNVs were found at a lower frequency (1.4%-19.7%) among the consensus sequences. Cancer patients displayed a significantly higher intrahost viral genetic diversity compared to healthcare workers. This difference was independent of SARS-CoV-2 Ct values obtained at the diagnostic tests, which did not differ between the two groups. The most common nucleotide changes of intrahost SNVs in both groups were consistent with APOBEC and ADAR activities. Intrahost genetic diversity in cancer patients was not associated with disease severity, use of corticosteroids, or use of antivirals, characteristics that could influence viral diversity. Moreover, the presence of metastasis, either in general or specifically in the lung, was not associated with intrahost diversity among cancer patients. Cancer patients carried significantly higher numbers of minor variants compared to non-cancer counterparts. Further studies on SARS-CoV-2 diversity in especially vulnerable patients will shed light onto the understanding of the basis of COVID-19 different outcomes in humans.

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