The microbiome is able to modulate immune responses, alter the physiology of the human organism, and increase the risk of viral infections and development of diseases such as cancer. In this review, ...we address changes in the cervical microbiota as potential biomarkers to identify the risk of cervical intraepithelial neoplasia (CIN) development and invasive cervical cancer in the context of human papillomavirus (HPV) infection. Current approaches for clinical diagnostics and the manipulation of microbiota with the use of probiotics and through microbiota transplantation are also discussed.
The human cervical microbiome is complex, and its role in health and disease has just begun to be elucidated. In this study, 57 cervical swab samples from 19 HIV/HPV co-infected women were analyzed ...for both virome and bacteriome composition. Virome analysis focused on circular DNA viruses through rolling circle amplification followed by next-generation sequencing (NGS). Data were assigned to virus families and genera, and HPV types were identified. NGS data of bacterial 16S from a subset of 24 samples were assigned to operational taxonomic units and classified according to vaginal microbiome community state types (CSTs). Four viral families were found:
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,
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. Papillomavirus reads were more abundant in women with premalignant cervical lesions, which were also strongly associated with multiple (≥3) high-risk HPV infection. Anellovirus read abundance was negatively correlated with host CD4+ T-cell counts. The bacteriome revealed the presence of CST III and CST IV, and women with ≥1% frequency of genomovirus or herpesvirus reads displayed an increased risk of carrying CST IV. By characterizing the composition of the cervical circular DNA viruses and the bacteriome of HIV/HPV co-infected women, we identified putative interactions between these two microorganism communities and their associations with patients' clinical characteristics, notably immunodeficiency status.
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.
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.
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.
HIV infection negatively impacted prognosis and mortality of DLBCL patients irrespective of cancer-related clinical factors.
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.
•HIV infection plays an important role in the prognosis of breast cancer.•Matching of HIV+ and HIV− patients for important breast cancer characteristics.•HIV+ patients exhibit worse overall survival when compared to HIV− patients.•Cancer patients should undergo appropriate HAART regimens.
The cervical microbiota composition and diversity of HIV-positive women in the postpartum period is unknown. Using a high-throughput bacterial 16S rRNA gene sequencing, we identified four community ...state types (CSTs). CST III (Lactobacillusdominant) and CST IV (IV-A, IV-B.1, IV-B.2; high-diversity) were found in 41% and 59% of samples, respectively. We did not find association of any CST to postpartum period (six or twelve months), HPV infection or cytology (normal or lesion). However, five bacterial genera were associated with cervical lesions (Gardnerella, Aerococcus, Schlegelella, Moryella and Bifidobacterium), with significant odds ratio (OR) of 40 (2.28-706) for the presence of Moryella and 3.5 (1.36-8.9) for Schlegelella. Longitudinal analysis of samples at postpartum that regressed (lesion to normal), progressed (normal to lesion) and maintained the cytology (lesion or normal) evidenced Gardnerella with a significantly higher abundance in regressing lesions. In the current study, we report the first data on the cervical microbiota of HIV-positive women in the postpartum period. Consistent with previous studies of HIV-negative cohorts, HIV-positive women present a stable cervical microbiota of high-diversity in the postpartum period. Our results highlight that specific microbiota species may serve as sensors for changes in the cervical microenvironment associated with cervical lesions.
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.
The APOBEC family of proteins comprises deaminase enzymes that edit DNA and/or RNA sequences. The APOBEC3 subgroup plays an important role on the innate immune system, acting on host defense against ...exogenous viruses and endogenous retroelements. The role of APOBEC3 proteins in the inhibition of viral infection was firstly described for HIV-1. However, in the past few years many studies have also shown evidence of APOBEC3 action on other viruses associated with human diseases, including HTLV, HCV, HBV, HPV, HSV-1, and EBV. APOBEC3 inhibits these viruses through a series of editing-dependent and independent mechanisms. Many viruses have evolved mechanisms to counteract APOBEC effects, and strategies that enhance APOBEC3 activity constitute a new approach for antiviral drug development. On the other hand, novel evidence that editing by APOBEC3 constitutes a source for viral genetic diversification and evolution has emerged. Furthermore, a possible role in cancer development has been shown for these host enzymes. Therefore, understanding the role of deaminases on the immune response against infectious agents, as well as their role in human disease, has become pivotal. This review summarizes the state-of-the-art knowledge of the impact of APOBEC enzymes on human viruses of distinct families and harboring disparate replication strategies.
Abstract Infection by human papillomavirus (HPV) is a necessary condition for development of cervical cancer, and has also been associated with malignancies of other body anatomical sites. Specific ...HPV types have been associated with premalignant lesions and invasive carcinoma, but mounting evidence suggests that within-type lineages and sublineages also display distinct biological characteristics associated with persistent infections and evolution to cervical cancer. In the present study, we have assessed HPV multiple infection and variation from a cohort of highly susceptible, HIV+ pregnant women using next-generation sequencing and an in-house pipeline for HPV full-length genome assembly. Seventy-two consensus sequences representing complete or near-complete (>97%) HPV genomes were assembled, spanning 28 different types. Genetic distance and phylogenetic analyses allowed us to propose the classification of novel HPV lineages and sublineages across nine HPV types, including two high-risk types. HPV diversity may be a hallmark of immunosuppressed patients upon HIV infection and AIDS progression.
The dynamics underlying severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection remain poorly understood. We identified a small cluster of patients in Brazil who experienced 2 ...episodes of coronavirus disease (COVID-19) in March and late May 2020. In the first episode, patients manifested an enhanced innate response compared with healthy persons, but neutralizing humoral immunity was not fully achieved. The second episode was associated with different SARS-CoV-2 strains, higher viral loads, and clinical symptoms. Our finding that persons with mild COVID-19 may have controlled SARS-CoV-2 replication without developing detectable humoral immunity suggests that reinfection is more frequent than supposed, but this hypothesis is not well documented.
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