RESUMO
The Oral HIV/AIDS Research Alliance (OHARA) was established in 2006 to provide the capacity to investigate the oral complications associated with HIV/AIDS within the ACTG infrastructure. Its goals were to explore the effects of potent antiretroviral therapy (ART) on the development of opportunistic infections, and variation and resistance of opportunistic pathogens in the context of immune suppression and long-term ART. The objectives of this talk, presented as part of a plenary session at the 7th World Workshop on Oral Health and Disease in AIDS, were to (i) provide an overview of OHARA's most recent research agenda, and how it evolved since OHARA's inception; (ii) describe OHARA's main accomplishments, including examples of research protocols completed and their key findings; and (iii) describe spin-off projects derived from OHARA, lessons learned, and future directions. OHARA has met its central goal and made key contributions to the field in several ways: (i) by developing/updating diagnostic criteria for oral disease endpoints commonly measured in OHARA protocols and in HIV/AIDS research in general and has creating standardized training modules, both for measuring these oral disease endpoints across clinical specialties, and for collecting oral fluid specimens; (ii) by implementing a total of nine protocols, six of which are completed. Three protocols involved domestic research sites, while three involved international research sites (in Africa, India, and South America); (iii) and by developing and validating a number of laboratory assays used in its protocols and in the field of oral HIV/AIDS research.
Assuntos
Pesquisa Biomédica , Candidíase Bucal/imunologia , Infecções por HIV/complicações , Infecções por HIV/imunologia , Infecções por Papillomavirus/imunologia , Sarcoma de Kaposi/virologia , Antirretrovirais/uso terapêutico , Candidíase Bucal/virologia , Infecções por HIV/tratamento farmacológico , Humanos , Infecções por Papillomavirus/virologiaRESUMO
Human herpesviruses (HHVs) and human papillomavirus (HPV) are common in the general population and, in immunocompetent people, are mostly carried asymptomatically. However, once an individual becomes immunocompromised by age, illness or HIV infection these dormant viruses can manifest and produce disease. In HIV-positive patients, there is an increased risk of disease caused by HHVs and HPV infections and cancers caused by the oncoviruses Epstein-Barr Virus, HHV-8 and HPV. This workshop examined four questions regarding the viruses associated with oral cancers and disease in the HIV-positive and -negative populations, the immune response, and biomarkers useful for accurate diagnostics of these infections and their sequalae. Each presenter identified a number of key areas where further research is required.
Assuntos
Coinfecção/complicações , Infecções por Vírus Epstein-Barr/complicações , Infecções por HIV/complicações , Neoplasias Bucais/virologia , Neoplasias Orofaríngeas/virologia , Infecções por Papillomavirus/complicações , Sarcoma de Kaposi/virologia , Biomarcadores , Coinfecção/imunologia , Infecções por Vírus Epstein-Barr/imunologia , Infecções por HIV/imunologia , Herpesvirus Humano 8 , Humanos , Doenças da Boca/virologia , Infecções por Papillomavirus/imunologia , Sarcoma de Kaposi/imunologiaAssuntos
Imidazóis/farmacologia , Peptídeos e Proteínas de Sinalização Intracelular/antagonistas & inibidores , Linfoma Folicular/tratamento farmacológico , Inibidores de Fosfoinositídeo-3 Quinase , Inibidores de Proteínas Quinases/farmacologia , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Quinolinas/farmacologia , Animais , Antineoplásicos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica , Apoptose/efeitos dos fármacos , Western Blotting , Ácidos Borônicos/farmacologia , Bortezomib , Proliferação de Células/efeitos dos fármacos , Feminino , Fatores de Transcrição Forkhead/fisiologia , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Linfoma Folicular/metabolismo , Linfoma Folicular/patologia , Camundongos , Camundongos Nus , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Pirazinas/farmacologia , RNA Mensageiro/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Serina-Treonina Quinases TOR , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
The replication and transcription activator protein, Rta, is encoded by Orf50 in Kaposi's sarcoma-associated herpesvirus (KSHV) and other known gammaherpesviruses including Epstein-Barr virus (EBV), rhesus rhadinovirus (RRV), herpesvirus saimiri (HVS), and murine herpesvirus 68 (MHV-68). Each Rta/Orf50 homologue of each gammaherpesvirus plays a pivotal role in the initiation of viral lytic gene expression and lytic reactivation from latency. Here we discuss the Rta/Orf50 of KSHV in comparison to the Rta/Orf50s of other gammaherpesviruses in an effort to identify structural motifs, mechanisms of action, and modulating host factors.