Core promoter: A critical region where the hepatitis B virus makes decisions

The core promoter (CP) of the viral genome plays an important role for hepatitis B virus (HBV) replication as it directs initiation of transcription for the synthesis of both the precore and pregenomic (pg) RNAs. The CP consists of the upper regulatory region and the basal core promoter (BCP). The CP overlaps with the 3’-end of the X open reading frames and the 5’-end of the precore region, and contains cis-acting elements that can independently direct transcription of the precore mRNA and pgRNA. Its transcription regulation is under strict control of viral and cellular factors. Even though this regulatory region exhibits high sequence conservation, when variations appear, they may contribute to the persistence of HBV within the host, leading to chronic infection and cirrhosis, and eventually, hepatocellular carcinoma. Among CP sequence variations, those occurring at BCP may dysregulate viral gene expression with emphasis in the hepatitis B e antigen, and contribute to disease progression. In this review these molecular aspects and pathologic topics of core promoter are deeply evaluated.Fil: Quarleri, Jorge Fabian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentin

An evaluation of the SARS-CoV-2 epidemic 16 days after the end of social confinement in Hungary

Differences in the rigor of confinement and other preventive policies between countries and the speed and degree with which these measures are relaxed affect both the public health of COVID-19 and its social and economic impact. In this Special Issue, Merkeley et al. describe the results of a comprehensive large-scale survey of present and past SARS-CoV-2 infection in Hungary after the relaxation of containment measures. Their results suggest that the implementation of effective preventive policies in Hungary effectively reduced COVID-19 morbidity and mortality rates. The data provided may inform decisions by public health officials worldwide, both with regards to the implementation of preventive societal measures and the formulation of exit strategies. Data in this report also emphasize the importance of sustainable strategies aimed to shield older adults from potential SARS-CoV-2 infection.Fil: Galvan, Veronica. University of Texas Health Science Center at Houston; Estados UnidosFil: Quarleri, Jorge Fabian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentin

Editorial: Comparison of antibody and T cell responses elicited by BBIBP-CorV (Sinopharm) and BNT162b2 (Pfizer-BioNTech) vaccines against SARS-CoV-2 in healthy adult humans

Vaccine development has become the main tool for reducing COVID-19 cases and the severity of the disease. Comparative analyses of adaptive immunity generated by different vaccines platforms are urgently needed. Multiple studies have compared different vaccines using similar platforms; however, comparative analyses of vaccines across different platforms are lacking. This Editorial provides a summary and commentary on the main findings reported in the observational and longitudinal study by Vályi-Nagy et al. (Geroscience 43:2321) that compared the adaptive (humoral and T cell-mediated) immune responses elicited by Sinopharm and BNT162b2 vaccines against SARS-CoV-2 virus among 57 healthy adult Hungarian volunteers.Fil: Galvan, Veronica. Oklahoma State University; Estados UnidosFil: Quarleri, Jorge Fabian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentin

Influence of HIV Infection and Antiretroviral Therapy on Bone Homeostasis

The human immunodeficiency virus type 1 (HIV)/AIDS pandemic represents the most significant global health challenge in modern history. This infection leads toward an inflammatory state associated with chronic immune dysregulation activation that tilts the immune-skeletal interface and its deep integration between cell types and cytokines with a strong influence on skeletal renewal and exacerbated bone loss...Fil: Delpino, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaFil: Quarleri, Jorge Fabian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentin

Influence of HIV Infection and Antiretroviral Therapy on Bone Homeostasis

The human immunodeficiency virus type 1 (HIV)/AIDS pandemic represents the most significant global health challenge in modern history. This infection leads toward an inflammatory state associated with chronic immune dysregulation activation that tilts the immune-skeletal interface and its deep integration between cell types and cytokines with a strong influence on skeletal renewal and exacerbated bone loss...Fil: Delpino, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaFil: Quarleri, Jorge Fabian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentin

SARS-CoV-2 interacts with renin-angiotensin system: impact on the central nervous system in elderly patients

SARS-CoV-2 is a recently identified coronavirus that causes the current pandemic disease known as COVID-19. SARS-CoV-2 uses angiotensin-converting enzyme 2 (ACE2) as a receptor, suggesting that the initial steps of SARS-CoV-2 infection may have an impact on the renin-angiotensin system (RAS). Several processes are influenced by RAS in the brain. The neurological symptoms observed in COVID-19 patients, including reduced olfaction, meningitis, ischemic stroke, cerebral thrombosis, and delirium, could be associated with RAS imbalance. In this review, we focus on the potential role of disturbances in the RAS as a cause for central nervous system sequelae of SARS-CoV-2 infection in elderly patients.Fil: Quarleri, Jorge Fabian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Delpino, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentin

Molecular mechanisms implicated in SARS-CoV-2 liver tropism

The coronavirus disease 2019 (COVID-19) pandemic is caused by severe acuterespiratory syndrome coronavirus 2 (SARS-CoV-2). Hepatic involvement iscommon in SARS-CoV-2-infected individuals. It is currently accepted that thedirect and indirect hepatic effects of SARS-CoV-2 infection play a significant rolein COVID-19. In individuals with pre-existing infectious and non-infectious liverdisease, who are at a remarkably higher risk of developing severe COVID-19 anddeath, this pathology is most medically relevant. This review emphasizes thecurrent pathways regarded as contributing to the gastrointestinal and hepaticailments linked to COVID-19-infected patients due to an imbalanced interactionamong the liver, systemic inflammation, disrupted coagulation, and the lung.Fil: Quarleri, Jorge Fabian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Delpino, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentin

SARS-CoV-2 Pathogenesis: Imbalance in the Renin-Angiotensin System Favors Lung Fibrosis

After SARS-CoV-2 infection, a major complication of those who survived to COVID-19 outbreak is the development of severe lung disease leading to pulmonary fibrosis. At earliest step of virus-host cell interaction when the SARS-CoV-2 interacts with the ACE2 receptor highly expressed in pneumocytes type II, a linkage is established between the renin-angiotensin-system (RAS) and the viral pathogenesis. Within this important system, the angiotensin-converting enzyme (ACE) is deputed to the conversion of angiotensin I to angiotensin II (AngII), a potent vasoconstrictive peptide involved directly in inflammation and fibrosis development. AngII is hydrolyzed by ACE2 to Ang1-7, triggering a cascade of events that counteract fibrosis. This imbalance is known to be due to inflammatory damage. However, because ACE2 is the receptor for SARS-Cov-2, we could also speculate that the virus per se could modulate its enzymatic activity. In our opinion the wound healing pathways that mediate tissue repair after SARS-CoV-2 mediated injury, should consider managing the imbalanced ACE/ACE2 axis. We hypothesize that the heptapeptide Ang1-7 could provide novel therapeutic interventions for pulmonary fibrosis patients. Understanding how the RAS, wound healing and other pro-fibrotic pathways act after viral infection should lead to novel therapeutics in the future.Fil: Delpino, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaFil: Quarleri, Jorge Fabian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentin

Astrocyte Apoptosis and HIV Replication Are Modulated in Host Cells Coinfected with Trypanosoma cruzi

The protozoan Trypanosoma cruzi is the etiological agent of Chagas disease. In immunosuppressed individuals, as it occurs in the coinfection with human immunodeficiency virus (HIV), the central nervous system may be affected. In this regard, reactivation of Chagas disease is severe and often lethal, and it accounts for meningoencephalitis. Astrocytes play a crucial role in the environment maintenance of healthy neurons; however, they can host HIV and T. cruzi. In this report, human astrocytes were infected in vitro with both genetically modified-pathogens to express alternative fluorophore. As evidenced by fluorescence microscopy and flow cytometry, HIV and T. cruzi coexist in the same astrocyte, likely favoring reciprocal interactions. In this context, lower rates of cell death were observed in both T. cruzi monoinfected-astrocytes and HIV-T. cruzi coinfection in comparison with those infected only with HIV. The level of HIV replication is significantly diminished under T. cruzi coinfection, but without affecting the infectivity of the HIV progeny. This interference with viral replication appears to be related to the T. cruzi multiplication rate or its increased intracellular presence but does not require their intracellular cohabitation or infected cell-to-cell contact. Among several Th1/Th2/Th17 profile-related cytokines, only IL-6 was overexpressed in HIV-T. cruzi coinfection exhibiting its cytoprotective role. This study demonstrates that T. cruzi and HIV are able to coinfect astrocytes thus altering viral replication and apoptosis.Fil: Urquiza, Javier Mariano. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Burgos, Juan Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Ojeda, Diego Sebastian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Pascuale, Carla Antonela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Leguizamon, Maria Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Quarleri, Jorge Fabian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentin

Molecular characterization of hepatitis C virus genotype 4 sequences in HIV-coinfected patients from Argentina

The prevalence of hepatitis C virus genotype 4 (HCV-4) is increasing in different parts of the World but in Latin America the data are still scarce. We aimed to characterize HCV-4 isolates from 383 HIV-coinfected patients in Argentina. Sequence analyses were based on the non-structural 5B region of HCV. Results from 18 patients indicated a genetic heterogeneity that involved three genotype 4 subtypes. Sequences were ascribed to subtype 4d (67%), 4a (22%) and 4m (11%). In spite of different sources of transmission were defined among patients, no statistical association was found with the genotype 4 subtype. The scenario is also compatible with multiple importation of the epidemic and there is no evidence for transmission–specific clusters or network-like transmission of HCV-4. This HCV-4 does not represent a recent introduction in Argentina, it circulates in all transmission groups and its presence is increasing among HIV-infected patients.Fil: Bolcic, Federico Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Jones, Leandro Roberto. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación Playa Unión. Estación de Fotobiología Playa Unión; ArgentinaFil: Laufer, Natalia Lorna. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Quarleri, Jorge Fabian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentin