ABSTRACT
ABSTRACT Background: Latent HIV-1 is a major hurdle in obtaining HIV-1 sustained virological remission (SVR). Here we explored histone deacetylation inhibition property of nicotinamide (NAM; n = 17) for the first time in comparison to a combination of methyltransferase inhibitors (MTIs; Chaetocin and BIX01294; n = 25) to reactivate latent HIV ex vivo in CD8-depleted PBMCs from antiretroviral treated aviremic individuals. Results: NAM reactivated HIV-1 from 13/17 (76.4%) samples compared to 20/25 (80.0%) using MTIs with mean viral load (VLs) of 4.32 and 3.22 log10 RNA copies/mL, respectively (p = 0.004). Mean purging time after NAM and MTIs stimulation was 5.1 and 6.75 days, respectively (p = 0.73). Viral purging in autologous cultures exhibited blunted HIV recovery with fluctuating VLs followed by a complete viral extinction when expanded in allogenic system. Electron microscopy from five supernatants revealed anomalous viral particles, with lack of complete viral genomes when characterized by ultradeep sequencing through metagenomics approach (n = 4). Conclusion: NAM alone was more potent HIV-1 activator than combination of MTIs, with potential of clinical use.
Subject(s)
Adult , Female , Humans , Male , Middle Aged , Young Adult , Quinazolines/pharmacology , Azepines/pharmacology , Virus Activation/drug effects , HIV Infections/virology , HIV-1/drug effects , Niacinamide/pharmacology , Methyltransferases/antagonists & inhibitors , Piperazines/pharmacology , Leukocytes, Mononuclear/virology , CD4-Positive T-Lymphocytes , Gene Expression Regulation, Viral , Virus Latency , Viral Load/drug effects , Viral Tropism/drug effectsABSTRACT
Human enteroviruses (EVs) are associated with a wide spectrum of human diseases. Here we report the complete genome sequences of one EV-C99 strain and one E29 strain obtained from children suffering from acute gastroenteritis, without symptoms of enteroviral syndromes. This is the first report of EV-C99 in South America, and the second E29 genome described worldwide. Continuous surveillance on EVs is vital to provide further understanding of the circulation of new or rare EV serotypes in the country. The present study also highlights the capacity of EVs to remain in silent circulation in populations.
Subject(s)
Humans , Male , Child, Preschool , Aged , RNA, Viral/genetics , Enterovirus B, Human/genetics , Enterovirus C, Human/genetics , Enterovirus Infections/virology , Phylogeny , Brazil , Enterovirus B, Human/isolation & purification , Enterovirus C, Human/isolation & purification , Feces/virologyABSTRACT
Human sapoviruses (HSaV) are considered important causative agents of acute gastroenteritis in humans worldwide. However, knowledge of the genetic characteristics of the whole genome of HSaV in Brazil is limited. Here we report the complete genome sequences of six HSaVs GI.2 and two GI.3 strains obtained from children with acute gastroenteritis in the Northern region of Brazil. Next generation sequencing was used to obtain the full genome and molecular characterization of the genome was performed. Phylogenetic analysis of the genome was also performed. Only one complete HSaV GI.2 genome characterization in the country precedes that of the present study. This is the first complete genome sequence of genotype GI.3 in Brazil. The data obtained in this investigation can contribute to the augmentation of the database on the molecular diversity of HSaVs strains circulating in Brazil, and to the improvement of current typing protocols.
Subject(s)
Humans , Child , Caliciviridae Infections/virology , Sapovirus/genetics , Gastroenteritis/virology , Phylogeny , Brazil , Acute Disease , Sequence Analysis, DNA , High-Throughput Nucleotide Sequencing , GenotypeABSTRACT
Hereditary angioedema is an autosomal dominant disease characterized by recurrent angioedema attacks with the involvement of multiple organs. The disease is unknown to many health professionals and is therefore underdiagnosed. Patients who are not adequately diagnosed and treated have an estimated mortality rate ranging from 25% to 40% due to asphyxiation by laryngeal angioedema. Intestinal angioedema is another important and incapacitating presentation that may be the main or only manifestation during an attack. In this article, a group of experts from the "Associação Brasileira de Alergia e Imunologia (ASBAI)" and the "Grupo de Estudos Brasileiro em Angioedema Hereditário (GEBRAEH)" has updated the Brazilian guidelines for the diagnosis and treatment of hereditary angioedema.
Subject(s)
Humans , Angioedemas, Hereditary/diagnosis , Brazil , Complement C4/analysis , Diagnosis, Differential , Complement C1 Inhibitor Protein/analysis , Angioedemas, Hereditary/classification , Angioedemas, Hereditary/physiopathologyABSTRACT
O angioedema hereditário é uma doença autossômica dominante caracterizada por crises de edema com o envolvimento de múltiplos órgãos. A doença é desconhecida por muitos profissionais da área da saúde e, portanto, subdiagnosticada. Os pacientes que não são diagnosticados e tratados adequadamente têm uma mortalidade estimada de 25% a 40%, devido ao angioedema da laringe, resultando em asfixia. O angioedema de alças intestinais é outra manifestação importante e incapacitante, que pode ser a principal ou a única durante uma crise da doença. Neste cenário, um grupo de especialistas da Associação Brasileira de Alergia e Imunologia (ASBAI) e do Grupo de Estudos Brasileiro em Angioedema Hereditário (GEBRAEH) atualizou as diretrizes para o diagnóstico e terapia do angioedema hereditário.
Hereditary angioedema is an autosomal dominant disease characterized by edema attacks with the involvement of multiple organs. The disease is unknown to many health professionals and is therefore underdiagnosed. Patients who are not adequately diagnosed and treated have an estimated mortality rate ranging from 25% to 40%, due to laryngeal angioedema, which results in asphyxia. Angioedema affecting bowel loops is another important, incapacitating presentation that may be the main or only manifestation during a crisis. In this scenario, a group of experts affiliated with Associação Brasileira de Alergia e Imunologia (ASBAI) and Grupo de Estudos Brasileiro em Angioedema Hereditário (GEBRAEH) has updated the guidelines for the diagnosis and treatment of hereditary angioedema.
Subject(s)
Humans , Male , Female , History, 21st Century , Guidelines as Topic , Allergy and Immunology , Angioedemas, Hereditary/drug therapy , Therapeutics , Diagnosis , Hereditary Angioedema Types I and IIABSTRACT
The Brazilian variant of human immunodeficiency virus type 1 (HIV-1) subtype B, (serotype B"-GWGR), has a tryptophan replacing the proline in position 328 the HIV-1 envelope. A longer median time period from infection to acquired immunodeficiency syndrome (AIDS) for serotype B (B"-GWGR) infected subjects compared to the B-GPGR US/European strain was reported. In a cohort study, in São Paulo city, 10 B"-GWGR patients had a statistically significant increased avidity of the anti-V3 antibodies, from 79 percent ± 33 percent to 85 percent ± 75 percent, versus from 48 percent ± 59 percent to 32 percent ± 17 percent for the 10 B-GPGR subjects (p = 0.02). The T CD4+ cells showed a mean increase of + 0.45 cells/month for the B-GPGR subjects and for B"-GWGR the slope was + 1.24 cells/month (p = 0.06), for 62 and 55 months of follow up, respectively. RNA plasma viral load decreased from 3.98 ± 1.75 to 2.16 ± 1.54 log10 in the B"-GWGR group while B-GPGR patients showed one log10 reduction in viral load from 4.09 ± 0.38 to 3.17 ± 1.47 log10 over time (p = 0.23), with a decreasing slope of 0.0042 ± log10,/month and 0.0080 ± log10/month, for B-GPGR and B"-GWGR patients, respectively (p = 0.53). Neither group presented any AIDS defining events during the study, according to Center for Diseases Control criteria. Although the sample size is small, these results may indicate that differences in the pathogenicity of the 2 HIV-1 B serotypes which co-circulate in Brazil may be correlated to the avidity of anti-V3 antibodies.
Subject(s)
Humans , Male , Female , Acquired Immunodeficiency Syndrome/immunology , Antibody Affinity , HIV Antibodies , Acquired Immunodeficiency Syndrome/virology , Brazil , Cohort Studies , Follow-Up Studies , Genetic Variation , HIV Antibodies , HIV Envelope Protein gp120 , RNA, Viral , Serotyping , Viral LoadABSTRACT
O objetivo deste estudo visou avaliar e comparar os métodos sorológicos (EIA-fase sólida e EIA-inibição) com os métodos moleculares (RFLP-Fok 1 e por seqüênciamento direto do gene env do HIV-1) identificando a variante brasileira BGWGR. A concordância do resultado entre os métodos EIA-fase sólida, RFLP, seqüenciamento direto para distinguir o BGWGR foi de / The purpose of this study was, to evaluate and compare, two serological methods EIA solid phase and EIA inhibition with molecular methods (Restriction Fragment Length Polymorphism (RFLP) and direct DNA sequencing, for identifying the HIV-1 Brazilian variant - subtype B"- GWGR. The agreement among, EIA solid phase, RFLP and direct DNA sequencing methods, to distinguish the Brazilian variant...