RESUMO
OBJECTIVE: To perform a molecular screening to detect infections by the mayaro virus and possible coinfections with Chikungunya during an outbreak in the state of Tocantins/Brazil in 2017. RESULTS: Of a total 102 samples analyzed in this study, 6 cases were identified with simultaneous infection between mayaro and chikungunya viruses (5.88%). In these 6 samples, the mean Cycle threshold (Ct) for CHIKV was 26.87 (SD ± 10.54) and for MAYV was 29.58 (SD ± 6.34). The mayaro sequences generated showed 95-100% identity to other Brazilian sequences of this virus and with other MAYV isolates obtained from human and arthropods in different regions of the world. The remaining samples were detected with CHIKV monoinfection (41 cases), DENV monoinfection (50 cases) and coinfection between CHIKV/DENV (5 cases). We did not detect MAYV monoinfections.
Assuntos
Febre de Chikungunya , Vírus Chikungunya , Coinfecção , Dengue , Brasil/epidemiologia , Febre de Chikungunya/diagnóstico , Febre de Chikungunya/epidemiologia , Vírus Chikungunya/genética , Coinfecção/epidemiologia , Dengue/epidemiologia , Surtos de Doenças , HumanosRESUMO
With each infectious pandemic or outbreak, the medical community feels the need to revisit basic concepts of immunology to understand and overcome the difficult times brought about by these infections. Regarding viruses, they have historically been responsible for many deaths, and such a peculiarity occurs because they are known to be obligate intracellular parasites that depend upon the host's cell machinery for their replication. Successful infection with the production of essential viral components requires constant viral evolution as a strategy to manipulate the cellular environment, including host internal factors, the host's nonspecific and adaptive immune responses to viruses, the metabolic and energetic state of the infected cell, and changes in the intracellular redox environment during the viral infection cycle. Based on this knowledge, it is fundamental to develop new therapeutic strategies for controlling viral dissemination, by means of antiviral therapies, vaccines, or antioxidants, or by targeting the inhibition or activation of cell signaling pathways or metabolic pathways that are altered during infection. The rapid recovery of altered cellular homeostasis during viral infection is still a major challenge. Here, we review the strategies by which viruses evade the host's immune response and potential tools used to develop more specific antiviral therapies to cure, control, or prevent viral diseases.
Assuntos
Evasão da Resposta Imune , Viroses/virologia , Fenômenos Fisiológicos Virais/imunologia , Vírus/imunologia , Animais , Humanos , Imunidade Inata , Redes e Vias Metabólicas , Replicação ViralRESUMO
Different therapeutic strategies have been investigated to target and eliminate HIV-1-infected cells by using armed antibodies specific to viral proteins, with varying degrees of success. Herein, we propose a new strategy by combining photodynamic therapy (PDT) with HIV Env-targeted immunotherapy, and refer to it as HIV photoimmunotherapy (PIT). A human anti-gp41 antibody (7B2) was conjugated to two photosensitizers (PSs) with different charges through different linking strategies; "Click" conjugation by using an azide-bearing porphyrin attached via a disulfide bridge linker with a drug-to-antibody ratio (DAR) of exactly 4, and "Lysine" conjugation by using phthalocyanine IRDye 700DX dye with average DARs of 2.1, 3.0 and 4.4. These photo-immunoconjugates (PICs) were compared via biochemical and immunological characterizations regarding the dosimetry, solubility, and cell targeting. Photo-induced cytotoxicity of the PICs were compared using assays for apoptosis, reactive oxygen species (ROS), photo-cytotoxicity, and confocal microscopy. Targeted phototoxicity seems to be primarily dependent on the binding of PS-antibody to the HIV antigen on the cell membrane, whilst being independent of the PS type. This is the first report of the application of PIT for HIV immunotherapy by killing HIV Env-expressing cells.
Assuntos
Ânions , Fármacos Anti-HIV/farmacologia , Cátions , Imunoconjugados/farmacologia , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Ânions/química , Fármacos Anti-HIV/química , Anticorpos Monoclonais , Apoptose/efeitos dos fármacos , Cátions/química , Linhagem Celular Tumoral , Células Cultivadas , Citometria de Fluxo , Imunofluorescência , HIV/efeitos dos fármacos , HIV/genética , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Humanos , Imunoconjugados/química , Fármacos Fotossensibilizantes/química , Espécies Reativas de Oxigênio/metabolismo , Replicação Viral/efeitos dos fármacos , Produtos do Gene env do Vírus da Imunodeficiência Humana/antagonistas & inibidores , Produtos do Gene env do Vírus da Imunodeficiência Humana/genética , Produtos do Gene env do Vírus da Imunodeficiência Humana/metabolismoRESUMO
In the present study, we investigated the influence of HIV-1 subtype in the response to the dendritic cell (DC) therapeutic vaccine for HIV. HIV-1 viral load and TCD8+/TCD4+ cell counts for up to 48 weeks after vaccination. Out of 19 immunized subjects, 13 were infected by subtype B, 5 by subtype F, and 1 by subtype D. Overall, 42.1% (8/19) achieved a viral load decline of ≥ 1 log(10) sustained up to 48 weeks after immunization. Such magnitude of viral load drop was seen in 80% (4/5) of subtype F infected patients, and in 23.0% (3/13) of the subtype B infected ones (p=0.08). Moreover, mean viral load decline was 1.32 log(10), for subtype F infected individuals compared to 0.5 log(10) among subtype B infected patients (p=0.01). The variation in TCD4+ cell count was not related to HIV-1 subtype. Larger studies are necessary to confirm the efficacy of this immunotherapy and the differential response according to the background genetic diversity of HIV-1.