Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 22
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
J Infect Dis ; 2021 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-34626109

RESUMO

Many characteristics associated with Ebola virus disease remain to be fully understood. It is known that direct contact with infected bodily fluids is an associated risk factor, but few studies have investigated parameters associated with transmission between individuals, such as the dose of virus required to facilitate spread and route of infection. Therefore, we sought to characterize the impact by route of infection, viremia, and viral shedding through various mucosae, with regards to intraspecies transmission of Ebola virus in a non-human primate model. Here, challenge via the esophagus or aerosol to the face did not result in clinical disease, although seroconversion of both challenged and contact animals was observed in the latter. Subsequent intramuscular or intratracheal challenges suggest that viral loads determine transmission likelihood to naïve animals in an intramuscular-challenge model, which is greatly facilitated in an intratracheal-challenge model where transmission from challenged to direct contact animal was observed consistently.

2.
Biomedicines ; 9(9)2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34572372

RESUMO

Adeno-associated virus (AAV) vector mediated expression of therapeutic monoclonal antibodies is an alternative strategy to traditional vaccination to generate immunity in immunosuppressed or immunosenescent individuals. In this study, we vectorized a human monoclonal antibody (31C2) directed against the spike protein of SARS-CoV-2 and determined the safety profile of this AAV vector in mice and sheep as a large animal model. In both studies, plasma biochemical parameters and hematology were comparable to untreated controls. Except for mild myositis at the site of injection, none of the major organs revealed any signs of toxicity. AAV-mediated human IgG expression increased steadily throughout the 28-day study in sheep, resulting in peak concentrations of 21.4-46.7 µg/ mL, demonstrating practical scale up from rodent to large animal models. This alternative approach to immunity is worth further exploration after this demonstration of safety, tolerability, and scalability in a large animal model.

3.
Sci Rep ; 11(1): 18204, 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34521922

RESUMO

Available therapeutics for autoimmune disorders focused on mitigating symptoms, rather than treating the cause of the disorder. A novel approach using adeno-associated virus (AAV) could restore tolerance to the autoimmune targets and provide a permanent treatment for autoimmune diseases. Here, we evaluated the ability of collagen II T-cell epitopes packaged in adeno-associated virus serotype 8 (AAV-8) vectors to reduce pathogenic cellular and humoral responses against collagen and to mitigate the disease in the collagen-induced arthritis mouse model. The cytokines and immune cells involved in the immune suppression were also investigated. Mice treated with AAV-8 containing collagen II T-cell epitopes demonstrated a significant reduction in the arthritis symptoms, pathogenic collagen specific antibody and T cell responses. The AAV-8 mediated immune suppression was mediated by increased interleukin-10 expression and regulatory T cells expansion. Altogether, this study strengthens the notion that AAV vectors are promising candidates for the treatment of autoimmune diseases.

7.
Microorganisms ; 8(12)2020 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-33322333

RESUMO

The prolonged treatment of immunosuppressed (IS) individuals with anti-influenza monotherapies may lead to the emergence of drug-resistant variants. Herein, we evaluated oseltamivir and polymerase inhibitors combinations against influenza A/H3N2 infections in an IS mouse model. Mice were IS with cyclophosphamide and infected with 3 × 103 PFU of a mouse-adapted A/Switzerland/9715293/2013 (H3N2) virus. Forty-eight hours post-infection, the animals started oseltamivir, favipiravir or baloxavir marboxil (BXM) as single or combined therapies for 10 days. Weight losses, survival rates and lung viral titers (LVTs) were determined. The neuraminidase (NA) and polymerase genes from lung viral samples were sequenced. All untreated animals died. Oseltamivir and favipiravir monotherapies only delayed mortality (the mean day to death (MDD) of 21.4 and 24 compared to 11.4 days for those untreated) while a synergistic improvement in survival (80%) and LVT reduction was observed in the oseltamivir/favipiravir group compared to the oseltamivir group. BXM alone or in double/triple combination provided a complete protection and significantly reduced LVTs. Oseltamivir and BXM monotherapies induced the E119V (NA) and I38T (PA) substitutions, respectively, while no resistance mutation was detected with combinations. We found that the multiple dose regimen of BXM alone provided superior benefits compared to oseltamivir and favipiravir monotherapies. Moreover, we suggest the potential for drug combinations to reduce the incidence of resistance.

8.
J Infect Dis ; 221(5): 701-706, 2020 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-30942884

RESUMO

BACKGROUND: In 2017, the Democratic Republic of the Congo (DRC) recorded its eighth Ebola virus disease (EVD) outbreak, approximately 3 years after the previous outbreak. METHODS: Suspect cases of EVD were identified on the basis of clinical and epidemiological information. Reverse transcription-polymerase chain reaction (RT-PCR) analysis or serological testing was used to confirm Ebola virus infection in suspected cases. The causative virus was later sequenced from a RT-PCR-positive individual and assessed using phylogenetic analysis. RESULTS: Three probable and 5 laboratory-confirmed cases of EVD were recorded between 27 March and 1 July 2017 in the DRC. Fifty percent of cases died from the infection. EVD cases were detected in 4 separate areas, resulting in > 270 contacts monitored. The complete genome of the causative agent, a variant from the Zaireebolavirus species, denoted Ebola virus Muyembe, was obtained using next-generation sequencing. This variant is genetically closest, with 98.73% homology, to the Ebola virus Mayinga variant isolated from the first DRC outbreaks in 1976-1977. CONCLUSION: A single spillover event into the human population is responsible for this DRC outbreak. Human-to-human transmission resulted in limited dissemination of the causative agent, a novel Ebola virus variant closely related to the initial Mayinga variant isolated in 1976-1977 in the DRC.


Assuntos
Surtos de Doenças , Ebolavirus/genética , Doença pelo Vírus Ebola/diagnóstico , Doença pelo Vírus Ebola/epidemiologia , Adolescente , Adulto , República Democrática do Congo/epidemiologia , Ebolavirus/imunologia , Feminino , Doença pelo Vírus Ebola/transmissão , Doença pelo Vírus Ebola/virologia , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Filogenia , RNA Viral/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Testes Sorológicos , Adulto Jovem
10.
J Infect Dis ; 218(suppl_5): S292-S296, 2018 11 22.
Artigo em Inglês | MEDLINE | ID: mdl-30325435

RESUMO

Detection of chains of transmission is critical to interrupt Ebola virus (EBOV) outbreaks. For >25 years, quantitative reverse transcription polymerase chain reaction performed on biological fluids has been the reference standard for EBOV detection and identification. In the current study, we investigated the use of environmental sampling to detect EBOV shed from probable case patients buried without the collection of bodily fluids. During the 2012 Bundibugyo virus (BDBV) outbreak in the Democratic Republic of the Congo, environmental samples were screened for BDBV RNA by means of real-time polymerase chain reaction. Low levels of BDBV genomic RNA were detected in a hospital and in a house. Detection of BDBV RNA in the house led to the identification of the last chain of transmission still active, which resulted in the safe burial of the person with the last laboratory-confirmed case of this outbreak. Overall, environmental sampling can fill specific gaps to help confirm EBOV positivity and therefore be of value in outbreak management.


Assuntos
Ebolavirus/genética , Doença pelo Vírus Ebola/virologia , Líquidos Corporais/virologia , República Democrática do Congo , Surtos de Doenças , Humanos , RNA Viral/genética
11.
J Infect Dis ; 214(suppl 3): S281-S289, 2016 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-27651412

RESUMO

Enhanced virulence and/or transmission of West African Ebola virus (EBOV) variants, which are divergent from their Central African counterparts, are suspected to have contributed to the sizable toll of the recent Ebola virus disease (EVD) outbreak. This study evaluated the pathogenicity and shedding in rhesus macaques infected with 1 of 2 West African isolates (EBOV-C05 or EBOV-C07) or a Central African isolate (EBOV-K). All animals infected with EBOV-C05 or EBOV-C07 died of EVD, whereas 2 of 3 EBOV-K-infected animals died. The viremia level was elevated 10-fold in EBOV-C05-infected animals, compared with EBOV-C07- or EBOV-K-infected animals. More-severe lung pathology was observed in 2 of 6 EBOV-C05/C07-infected macaques. This is the first detailed analysis of the recently circulating EBOV-C05/C07 in direct comparison to EBOV-K with 6 animals per group, and it showed that EBOV-C05 but not EBOV-C07 can replicate at higher levels and cause more tissue damage in some animals. Increased virus shedding from individuals who are especially susceptible to EBOV replication is possibly one of the many challenges facing the community of healthcare and policy-making responders since the beginning of the outbreak.


Assuntos
Ebolavirus/patogenicidade , Doença pelo Vírus Ebola/virologia , Animais , Ebolavirus/fisiologia , Doença pelo Vírus Ebola/patologia , Humanos , Macaca mulatta , Especificidade da Espécie , Viremia , Virulência , Eliminação de Partículas Virais
12.
Sci Transl Med ; 8(329): 329ra33, 2016 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-26962157

RESUMO

The 2014-2015 Ebola virus (EBOV) outbreak in West Africa highlighted the urgent need for specific therapeutic interventions for infected patients. The human-mouse chimeric monoclonal antibody (mAb) cocktail ZMapp, previously shown to be efficacious in EBOV (variant Kikwit) lethally infected nonhuman primates (NHPs) when administration was initiated up to 5 days, was used in some patients during the outbreak. We show that a two-antibody cocktail, MIL77E, is fully protective in NHPs when administered at 50 mg/kg 3 days after challenge with a lethal dose of EBOV variant Makona, the virus responsible for the ongoing 2014-2015 outbreak, whereas a similar formulation of ZMapp protected two of three NHPs. The chimeric MIL77E mAb cocktail is produced in engineered Chinese hamster ovary cells and is based on mAbs c13C6 and c2G4 from ZMapp. The use of only two antibodies in MIL77E opens the door to a pan-ebolavirus cocktail.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Ebolavirus/imunologia , Doença pelo Vírus Ebola/tratamento farmacológico , Doença pelo Vírus Ebola/prevenção & controle , Animais , Células CHO , Cromatografia Líquida , Cricetinae , Cricetulus , Feminino , Cobaias , Macaca , Peptídeo-N4-(N-acetil-beta-glucosaminil) Asparagina Amidase/metabolismo
13.
J Immunol Methods ; 425: 69-78, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26099800

RESUMO

The majority of vaccines and several treatments are administered by intramuscular injection. The aim is to engage and activate immune cells, although they are rare in normal skeletal muscle. The phenotype and function of resident as well as infiltrating immune cells in the muscle after injection are largely unknown. While methods for obtaining and characterizing murine muscle cell suspensions have been reported, protocols for nonhuman primates (NHPs) have not been well defined. NHPs comprise important in vivo models for studies of immune cell function due to their high degree of resemblance with humans. In this study, we developed and systematically compared methods to collect vaccine-injected muscle tissue to be processed into single cell suspensions for flow cytometric characterization of immune cells. We found that muscle tissue processed by mechanical disruption alone resulted in significantly lower immune cell yields compared to enzymatic digestion using Liberase. Dendritic cell subsets, monocytes, macrophages, neutrophils, B cells, T cells and NK cells were readily detected in the muscle by the classic human markers. The methods for obtaining skeletal muscle cell suspension established here offer opportunities to increase the understanding of immune responses in the muscle, and provide a basis for defining immediate post-injection vaccine responses in primates.


Assuntos
Macaca/imunologia , Músculo Esquelético/imunologia , Animais , Células Dendríticas/imunologia , Citometria de Fluxo/métodos , Linfócitos/imunologia , Macrófagos/imunologia , Monócitos/imunologia , Neutrófilos/imunologia , Vacinas/imunologia
14.
J Infect Dis ; 212 Suppl 2: S389-97, 2015 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-26038398

RESUMO

In nonhuman primates, complete protection against an Ebola virus (EBOV) challenge has previously been achieved after a single injection with several vaccine platforms. However, long-term protection against EBOV after a single immunization has not been demonstrated to this date. Interestingly, prime-boost regimens have demonstrated longer protection against EBOV challenge, compared with single immunizations. Since prime-boost regimens have the potential to achieve long-term protection, determining optimal vector combinations is crucial. However, testing prime-boost efficiency in long-term protection studies is time consuming and resource demanding. Here, we investigated the optimal prime-boost combination, using DNA, porcine-derived adeno-associated virus serotype 6 (AAV-po6), and human adenovirus serotype 5 (Ad5) vector, in a short-term protection study in the mouse model of EBOV infection. In addition, we also investigated which immune parameters were indicative of a strong boost. Each vaccine platform was titrated in mice to identify which dose (single immunization) induced approximately 20% protection after challenge with a mouse-adapted EBOV. These doses were then used to determine the protection efficacy of various prime-boost combinations, using the same mouse model. In addition, humoral and cellular immune responses against EBOV glycoprotein were analyzed by an enzyme-linked immunosorbent assay, a neutralizing antibody assay, and an interferon γ-specific enzyme-linked immunospot assay. When DNA was used as a prime, Ad5 boost induced the best protection, which correlated with a higher cellular response. In contrast, when AAV-po6 or Ad5 were injected first, better protection was achieved after DNA boost, and this correlated with a higher total glycoprotein-specific immunoglobulin G titer. Prime-boost regimens using independent vaccine platforms may provide a useful strategy to induce long-term immune protection against filoviruses.


Assuntos
Vacinas contra Ebola/imunologia , Ebolavirus/imunologia , Doença pelo Vírus Ebola/imunologia , Adenovírus Humanos/imunologia , Animais , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Dependovirus/imunologia , Ensaio de Imunoadsorção Enzimática/métodos , ELISPOT/métodos , Vetores Genéticos/imunologia , Glicoproteínas/imunologia , Doença pelo Vírus Ebola/virologia , Humanos , Imunidade Celular/imunologia , Imunidade Humoral/imunologia , Imunização Secundária/métodos , Imunoglobulina G/imunologia , Camundongos , Suínos , Vacinação/métodos , Proteínas Virais/imunologia
15.
Hum Vaccin Immunother ; 10(10): 2875-84, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25483662

RESUMO

Pre-existing immunity against human adenovirus (HAd) serotype 5 derived vector in the human population is widespread, thus hampering its clinical use. Various components of the immune system, including neutralizing antibodies (nAbs), Ad specific T cells and type I IFN activated NK cells, contribute to dampening the efficacy of Ad vectors in individuals with pre-existing Ad immunity. In order to circumvent pre-existing immunity to adenovirus, numerous strategies, such as developing alternative Ad serotypes, varying immunization routes and utilizing prime-boost regimens, are under pre-clinical or clinical phases of development. However, these strategies mainly focus on one arm of pre-existing immunity. Selection of alternative serotypes has been largely driven by the absence in the human population of nAbs against them with little attention paid to cross-reactive Ad specific T cells. Conversely, varying the route of immunization appears to mainly rely on avoiding Ad specific tissue-resident T cells. Finally, prime-boost regimens do not actually circumvent pre-existing immunity but instead generate immune responses of sufficient magnitude to confer protection despite pre-existing immunity. Combining the above strategies and thus taking into account all components regulating pre-existing Ad immunity will help further improve the development of Ad vectors for animal and human use.


Assuntos
Infecções por Adenovirus Humanos/prevenção & controle , Adenovírus Humanos/imunologia , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Imunização/métodos , Infecções por Adenovirus Humanos/imunologia , Humanos , Imunidade Celular/imunologia , Imunidade Humoral/imunologia , Imunidade Inata/imunologia , Interferon Tipo I/imunologia , Células Matadoras Naturais , Linfócitos T/imunologia
16.
Vaccine ; 32(43): 5722-9, 2014 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-25173474

RESUMO

Ebola virus (EBOV) infections cause lethal hemorrhagic fever in humans, resulting in up to 90% mortality. EBOV outbreaks are sporadic and unpredictable in nature; therefore, a vaccine that is able to provide durable immunity is needed to protect those who are at risk of exposure to the virus. This study assesses the long-term efficacy of the vesicular stomatitis virus (VSV)-based vaccine (VSVΔG/EBOVGP) in two rodent models of EBOV infection. Mice and guinea pigs were first immunized with 2×10(4) or 2×10(5) plaque forming units (PFU) of VSVΔG/EBOVGP, respectively. Challenge of mice with a lethal dose of mouse-adapted EBOV (MA-EBOV) at 6.5 and 9 months after vaccination provided complete protection, and 80% (12 of 15 survivors) protection at 12 months after vaccination. Challenge of guinea pigs with a lethal dose of guinea pig-adapted EBOV (GA-EBOV) at 7, 12 and 18 months after vaccination resulted in 83% (5 of 6 survivors) at 7 months after vaccination, and 100% survival at 12 and 18 months after vaccination. No weight loss or clinical signs were observed in the surviving animals. Antibody responses were analyzed using sera from individual rodents. Levels of EBOV glycoprotein-specific IgG antibody measured immediately before challenge appeared to correlate with protection. These studies confirm that vaccination with VSVΔG/EBOVGP is able to confer long-term protection against Ebola infection in mice and guinea pigs, and support follow-up studies in non-human primates.


Assuntos
Vacinas contra Ebola/imunologia , Doença pelo Vírus Ebola/prevenção & controle , Vesiculovirus/imunologia , Proteínas do Envelope Viral/imunologia , Animais , Anticorpos Antivirais/sangue , Formação de Anticorpos , Ebolavirus , Feminino , Cobaias , Imunoglobulina G/sangue , Camundongos Endogâmicos BALB C
17.
Nature ; 514(7520): 47-53, 2014 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-25171469

RESUMO

Without an approved vaccine or treatments, Ebola outbreak management has been limited to palliative care and barrier methods to prevent transmission. These approaches, however, have yet to end the 2014 outbreak of Ebola after its prolonged presence in West Africa. Here we show that a combination of monoclonal antibodies (ZMapp), optimized from two previous antibody cocktails, is able to rescue 100% of rhesus macaques when treatment is initiated up to 5 days post-challenge. High fever, viraemia and abnormalities in blood count and blood chemistry were evident in many animals before ZMapp intervention. Advanced disease, as indicated by elevated liver enzymes, mucosal haemorrhages and generalized petechia could be reversed, leading to full recovery. ELISA and neutralizing antibody assays indicate that ZMapp is cross-reactive with the Guinean variant of Ebola. ZMapp exceeds the efficacy of any other therapeutics described so far, and results warrant further development of this cocktail for clinical use.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Anticorpos Antivirais/uso terapêutico , Doença pelo Vírus Ebola/tratamento farmacológico , Imunização Passiva , Sequência de Aminoácidos , Animais , Anticorpos Monoclonais/imunologia , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/uso terapêutico , Anticorpos Antivirais/imunologia , Reações Cruzadas/imunologia , Ebolavirus/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Guiné , Cobaias , Doença pelo Vírus Ebola/sangue , Doença pelo Vírus Ebola/imunologia , Doença pelo Vírus Ebola/virologia , Macaca mulatta/imunologia , Macaca mulatta/virologia , Masculino , Dados de Sequência Molecular , Alinhamento de Sequência , Proteínas do Envelope Viral/química , Proteínas do Envelope Viral/imunologia , Viremia/tratamento farmacológico , Viremia/imunologia , Viremia/virologia
18.
Curr Opin Virol ; 2(3): 324-9, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22560007

RESUMO

Because of high case fatality proportions, person-to-person transmission, and potential use in bioterrorism, the development of a vaccine against ebolavirus remains a top priority. Although no licensed vaccine or treatment against ebolavirus is currently available, progress in preclinical testing of countermeasures has been made. Here, we will review ebolavirus vaccine candidates and considerations for their use in humans and wild apes.


Assuntos
Vacinas contra Ebola/administração & dosagem , Vacinas contra Ebola/imunologia , Ebolavirus/imunologia , Doença pelo Vírus Ebola/prevenção & controle , Doença pelo Vírus Ebola/veterinária , Vacinação/métodos , Animais , Pesquisa Biomédica/tendências , Doença pelo Vírus Ebola/epidemiologia , Hominidae , Humanos
19.
PLoS Pathog ; 6: e1000975, 2010 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-20617170

RESUMO

CD4(+) T cell loss is central to HIV pathogenesis. In the initial weeks post-infection, the great majority of dying cells are uninfected CD4(+) T cells. We previously showed that the 3S motif of HIV-1 gp41 induces surface expression of NKp44L, a cellular ligand for an activating NK receptor, on uninfected bystander CD4(+) T cells, rendering them susceptible to autologous NK killing. However, the mechanism of the 3S mediated NKp44L surface expression on CD4(+) T cells remains unknown. Here, using immunoprecipitation, ELISA and blocking antibodies, we demonstrate that the 3S motif of HIV-1 gp41 binds to gC1qR on CD4(+) T cells. We also show that the 3S peptide and two endogenous gC1qR ligands, C1q and HK, each trigger the translocation of pre-existing NKp44L molecules through a signaling cascade that involves sequential activation of PI3K, NADPH oxidase and p190 RhoGAP, and TC10 inactivation. The involvement of PI3K and NADPH oxidase derives from 2D PAGE experiments and the use of PIP3 and H2O2 as well as small molecule inhibitors to respectively induce and inhibit NKp44L surface expression. Using plasmid encoding wild type or mutated form of p190 RhoGAP, we show that 3S mediated NKp44L surface expression on CD4(+) T cells is dependent on p190 RhoGAP. Finally, the role of TC10 in NKp44L surface induction was demonstrated by measuring Rho protein activity following 3S stimulation and using RNA interference. Thus, our results identify gC1qR as a new receptor of HIV-gp41 and demonstrate the signaling cascade it triggers. These findings identify potential mechanisms that new therapeutic strategies could use to prevent the CD4(+) T cell depletion during HIV infection and provide further evidence of a detrimental role played by NK cells in CD4(+) T cell depletion during HIV-1 infection.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Proteína gp41 do Envelope de HIV/metabolismo , Peróxido de Hidrogênio/metabolismo , Receptor 2 Desencadeador da Citotoxicidade Natural/biossíntese , Fosfatidilinositol 3-Quinases/fisiologia , Motivos de Aminoácidos/fisiologia , Proteínas de Transporte/metabolismo , Fatores de Troca do Nucleotídeo Guanina/metabolismo , Humanos , Proteínas Mitocondriais/metabolismo , Modelos Biológicos , NADPH Oxidases/metabolismo , Transporte Proteico/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Proteínas Repressoras/metabolismo , Transdução de Sinais
20.
J Acquir Immune Defic Syndr ; 53(5): 564-73, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20147841

RESUMO

BACKGROUND: Recent evidence suggests that natural killer (NK) cells play a crucial role in the HIV pathogenesis. Long-term nonprogressor (LTNP) and HIV controllers are rare HIV-infected patients who control viral replication and show delayed disease progression. They represent fascinating models of natural protection against disease progression and for studying the immunological response to the virus. METHODS: We have conducted an extensive analysis of the phenotypic and functional properties of CD56, CD56 and CD56/CD16 NK cell subsets from LTNP and HIV-controllers, and compared them with HIV progressors and healthy donors. RESULTS: Hierarchical clustering analysis of NK phenotypic markers revealed that LTNP and HIV controllers, exhibit peculiar phenotypic features, associated with high levels of interferon-g, activation markers, and cytolytic activity in CD3CD56 NK cells against K562 target cells. More importantly, cytolytic activity against autologous CD4 T cells is abrogated after treatment with anti-NKp44L mAb, in LTNP and HIV progressors, suggesting a key role of NKp44L. In contrast, in HIV controllers and healthy donors, NKp44L expression on CD4 T cells and autologous NK lysis were both poorly detected. CONCLUSIONS: These results show that NK cells from LTNP and HIV controllers display phenotypic and functional features and suggest a consistent continuous involvement of the innate immune response in the failure to control viral replication. Collectively, these data may have important implication in the design of new anti-HIV therapeutical strategies based on the particular functional activity of NK cells.


Assuntos
Infecções por HIV/imunologia , Sobreviventes de Longo Prazo ao HIV , HIV/imunologia , Células Matadoras Naturais/imunologia , Complexo CD3/imunologia , Antígeno CD56/imunologia , Análise por Conglomerados , Citotoxicidade Imunológica , Citometria de Fluxo , Infecções por HIV/virologia , Humanos , Imunidade Inata/imunologia , Imunofenotipagem , Células K562 , Células Matadoras Naturais/virologia , Receptor 2 Desencadeador da Citotoxicidade Natural/imunologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...