RESUMO
During the acute phase of HIV-1 infection, a strong readaptation occurs in the viral population. Our objective was to analyze the post-transmission mutations associated with escape to the cytotoxic immune response and its relationship with the progression of the infection. In this study, a total of 17 patients were enrolled during acute/early primary HIV infection and 8 subjects that were the HIV positive partner resulting in 8 transmission pairs. Genotyping of the genetic polymorphisms of HLA class I A and B was performed using PCR-SSOP. Viral RNA extraction was from plasma. 570 single Gag-gene amplifications were obtained by limiting-dilution RT-PCR. Epitope prediction was performed with NetMHC CBS prediction server for the 19 HLA-A and B alleles. Cytotoxic response prediction was performed by using the IEDB Analysis Resource. From our results, we deduce that the transmitted CTL / gag escape frequency in the founder virus was at least double compared to the post-transmission events. Additionally, by means of an algorithm that combines these frequencies, we observed that the founder viruses better adapted to the HLA A / B alleles of the recipient could contribute to a greater progression of the infection. Our results suggest that there is a large adaptation of HIV-1 to the HLA A / B alleles prevalent in our population. However, despite this adaptive advantage, the virus needs to make "readjustments" through new escape and compensatory mutations. Interestingly, according to our results, this readaptation could have a role in the progression of the infection.
Assuntos
Infecções por HIV/virologia , HIV-1/genética , Adulto , Alelos , Argentina , Biologia Computacional , Epitopos de Linfócito T/genética , Epitopos de Linfócito T/imunologia , Feminino , Genótipo , Infecções por HIV/imunologia , HIV-1/imunologia , Humanos , Masculino , Mutação/genética , Mutação/imunologia , RNA Viral/genética , RNA Viral/imunologia , Linfócitos T Citotóxicos/imunologia , Produtos do Gene gag do Vírus da Imunodeficiência Humana/genética , Produtos do Gene gag do Vírus da Imunodeficiência Humana/imunologiaRESUMO
The HIV epidemic in Argentina is characterized by the high prevalence of infections caused by subtype B and BF variants. In this study, the Nef protein was used as a tool to study the impact of HIV-1 BF variants in the design of future vaccines. DNA and MVA vectors expressing Nef of the CRF12_BF recombinant form of HIV-1 were generated and characterized. After the administration of single DNAprime/MVAboost immunization schedules in Balb/c mice we found that NefBF delivered from these vectors generated a response of high specificity with low cross-reactivity against subtype B. But, when a more potent response was induced after 3 priming DNA doses and a booster with MVA virus, cross-reactivity against NefB was detected, although of lower magnitude than the NefBF specific. These results will be pivotal for vaccines designs in our region, indicating that antigens from these viral variants must be considered for a future vaccine.
Assuntos
Vacinas contra a AIDS/imunologia , HIV-1/imunologia , Vacinas de DNA/imunologia , Vaccinia virus/genética , Produtos do Gene nef do Vírus da Imunodeficiência Humana/imunologia , Vacinas contra a AIDS/genética , Animais , Anticorpos Neutralizantes/sangue , Linhagem Celular , Chlorocebus aethiops , Cricetinae , Reações Cruzadas , Vetores Genéticos , Anticorpos Anti-HIV/sangue , Infecções por HIV/prevenção & controle , HIV-1/genética , Imunização Secundária/métodos , Interferon gama/metabolismo , Leucócitos Mononucleares/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Vacinas de DNA/genética , Vacinas de Subunidades Antigênicas/genética , Vacinas de Subunidades Antigênicas/imunologia , Produtos do Gene nef do Vírus da Imunodeficiência Humana/genéticaRESUMO
The study of digestive pathophysiology and scientific advnces showed a better knowledge related to the invaluable usefulness of the nutritional stage and the importance of the intestinal route for feeding purposes. In this consideration, the enteral feeding is elective considered not only in patients with an adquate digestive function but further more with some difficulties or swallowing disturbances, but also in those patients that because of their underlying pathology can not feed tremselves by mouth in a temporary way. The caloric support by the intestinal route con be performed by nasoenteral tubes or osteomas as gastrostomies, gastrojejunostomy, jejunostomies and hepato-jejunostomies. The aim of this report eas to show our results with the different ways of enteral feeding. These results are presented and discussed.
Assuntos
Humanos , Nutrição Enteral , Dilatação Gástrica , Bombas de Infusão , Procedimentos Cirúrgicos Minimamente Invasivos , Transtornos de Deglutição/patologiaRESUMO
The study of digestive pathophysiology and scientific advnces showed a better knowledge related to the invaluable usefulness of the nutritional stage and the importance of the intestinal route for feeding purposes. In this consideration, the enteral feeding is elective considered not only in patients with an adquate digestive function but further more with some difficulties or swallowing disturbances, but also in those patients that because of their underlying pathology can not feed tremselves by mouth in a temporary way. The caloric support by the intestinal route con be performed by nasoenteral tubes or osteomas as gastrostomies, gastrojejunostomy, jejunostomies and hepato-jejunostomies. The aim of this report eas to show our results with the different ways of enteral feeding. These results are presented and discussed.(AU)
Assuntos
Humanos , Nutrição Enteral , Bombas de Infusão , Transtornos de Deglutição/patologia , Dilatação Gástrica , Procedimentos Cirúrgicos Minimamente InvasivosRESUMO
The impact of HIV-1 genetic diversity on the performance of laboratory testing is an issue that has to be monitored continuously. An "in-house" real-time PCR assay was developed by the Agence Nationale de Recherche sur le SIDA (ANRS) in France for viral load (VL) quantitation based on the amplification of the HIV-1 long terminal repeat (LTR) region. This technology has not been used in Argentina yet and considering the HIV-1 diversity in the country, a comparative analysis of this assay was undertaken versus the Versant HIV-1 RNA 3.0 Assay (b-DNA). The performance was assessed on 30 drug-naïve HIV-1 infected patients who were characterized previously by phylogenetic analysis of the pol and vpu gene. The results showed that there is a significant linear correlation between values of transformed viral load logarithms measured by both, bDNA and real-time PCR assay and that this assay can be used to quantify viral load in samples from BF-infected patients with the same accuracy and reliability as for B subtype samples. The use of "in-house" real-time PCR to measure DNA in PBMCs correlated strongly with the HIV-1 RNA levels in all specimens.