Apoptosis de neutrófilos en la infección asintomática por Virus de la Inmunodeficiencia Humana / Neutrophil apoptosis in asymptomatic Human Immunodeficiency Virus infection

En los últimos años se ha determinado que los neutrófilos son células altamente versátiles y sofisticadas, cuyas funciones van mucho más allá de la eliminación de los microorganismos. En la infección con el Virus de Inmunodeficiencia Humana (HIV), si bien el papel de los neutrófilos no está totalmente caracterizado, actualmente está claro que la relación entre los neutrófilos y el virus es mucho más compleja de lo que se pensaba. Los objetivos de este trabajo fueron evaluar en pacientes con infección asintomática, y sin tratamiento antirretroviral, el efecto de la infección por el HIV sobre la muerte celular de los neutrófilos y la expresión de receptores de superficie. En pacientes seropositivos sin tratamiento hubo un aumento de la apoptosis temprana de los neutrófilos en relación a los grupos controles. Esta apoptosis aumentada no depende de la activación de la vía extrínseca o intrínseca. En estos pacientes hubo un aumento de la expresión de TLR2 que, unido al aumento de la apoptosis temprana, podría ser indicativo de un fenotipo activado de los neutrófilos. En conclusión, este trabajo aporta información sobre aspectos relacionados con la apoptosis de los neutrófilos en estadios tempranos de la infección por HIV, contribuyendo así a una mayor comprensión acerca del efecto de este virus sobre componentes de la respuesta inmune innata.

In recent years it has been determined that neutrophils are highly versatile and sophisticated cells whose functions go far beyond the elimination of microorganisms. In Human Immunodeficiency Virus (HIV) infection, the role of neutrophils is not fully characterized but it is now clear that the relationship between neutrophils and HIV is much more complex than previously thought. The aims of this study were to evaluate the effect of HIV infection on neutrophil cell death and the expression of surface molecules on neutrophils in patients with asymptomatic infection and without antiretroviral treatment (ART). In HIV seropositive patients without antiretroviral therapy there was an increase in the early apoptosis of neutrophils in relation to the control groups. This increased apoptosis does not depend on the activation of the extrinsic or intrinsic pathway. In these patients there was an increase in the expression of TLR2 which, together with the increase of early apoptosis, could be indicative of an activated phenotype of neutrophils. In conclusion, this study provides information on aspects related to the apoptosis of neutrophils in early stages of HIV infection and therefore contributes to a better understanding of the effect of this virus on components of the innate immune response.

Nos últimos anos, determinou-se que os neutrófilos são células altamente versáteis e sofisticadas, cujas funções vão muito além da eliminação dos microrganismos. Na infecção pelo HIV, embora o papel dos neutrófilos não esteja totalmente caracterizado, atualmente fica bem claro que a relação entre os neutrófilos e o vírus é muito mais complexa do que se pensava anteriormente. Os objetivos deste trabalho foram avaliar em pacientes com infecção assintomática, e sem tratamento antirretroviral, o efeito da infecção pelo HIV na morte celular dos neutrófilos e a expressão de receptores de superfície. Nos pacientes soropositivos sem tratamento, houve um aumento da apoptose precoce dos neutrófilos em relação aos grupos controle.Esta apoptose aumentada não depende da ativação da via extrínseca ou intrínseca. Nestes pacientes, houve um aumento da expressão de TLR2 que, juntamente com o aumento da apoptose precoce, poderia ser indicativo de um fenótipo ativado dos neutrófilos. Em conclusão, este trabalho fornece informações sobre aspectos relacionados com a apoptose dos neutrófilos em estágios precoces da infecção pelo HIV, contribuindo desse modo para uma maior compreensão sobre o efeito deste vírus nos componentes da resposta imune inata.

mCSM-AB: a web server for predicting antibody-antigen affinity changes upon mutation with graph-based signatures.

Computational methods have traditionally struggled to predict the effect of mutations in antibody-antigen complexes on binding affinity. This has limited their usefulness during antibody engineering and development, and their ability to predict biologically relevant escape mutations. Here we present mCSM-AB, a user-friendly web server for accurately predicting antibody-antigen affinity changes upon mutation which relies on graph-based signatures. We show that mCSM-AB performs better than comparable methods that have been previously used for antibody engineering. mCSM-AB web server is available at http://structure.bioc.cam.ac.uk/mcsm_ab.

Human immunodeficiency virus type 1 Brazilian subtype B variant showed an increasing avidity of the anti-V3 antibodies over time compared to the subtype B US/European strain in São Paulo, Brazil.

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% +/- 33% to 85% +/- 75%, versus from 48% +/- 59% to 32% +/- 17% 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.

HIV specific humoral immune response in Rio de Janeiro, Brazil. The HEC/Fiocruz AIDS Clinical Research Group.

Efforts to characterize HIV-1 polymorphism and anti-HIV immune response are being made in areas where anti-HIV/AIDS vaccines are to be employed. Anti-HIV-1 humoral immune response is being studied in infected individuals residents in Rio de Janeiro, in distinct cohorts involving recent seroconvertors, pregnant women or intravenous drug users (IDU). Comparative analyses of specificity of antibody response towards epitopes important for anti-HIV-1 immune response indicate quantitative differences between cohorts, with an exceptionally strong response in IDUs and weakest response in pregnant women. However, a comparative analysis between pregnant women cohorts from Rio de Janeiro and Rio Grande do Sul indicated an even lower response (with exception of the anti-V3-C clade peptide recognition) for the southern cohort. Studies analysing the immune function of the humoral response indicate a quite elevated occurrence of antibodies capable for neutralizing heterologous primary HIV-1 isolates from Rio de Janeiro. Attempts to correlate seroreactivity with HIV-1 neutralization with respect to HIV-1 polymorphism were not very successful: while the Brazilian B clade B " variant could be recognized by binding assays, no significant distinction of HIV-1 clades/variants was observed in viral neutralization assays.