RESUMO
Bupropion is the only FDA - approved synthetic cathinone, with increasing popularity in clinical practice due to its wide range of action, and lack of sexual side effects. However, its stimulant effect similar to amphetamines has growing the concern regarding its recreational use.
Assuntos
Antidepressivos de Segunda Geração , Insuflação , Humanos , Bupropiona/efeitos adversos , Antidepressivos de Segunda Geração/efeitos adversosRESUMO
γ-Herpesviruses establish latent infections of lymphocytes and drive their proliferation, causing cancers and motivating a search for vaccines. Effective vaccination against murid herpesvirus-4 (MuHV-4)-driven lymphoproliferation by latency-impaired mutant viruses suggests that lytic access to the latency reservoir is a viable target for control. However, the vaccines retained the immunogenic MuHV-4 M2 latency gene. Here, a strong reduction in challenge virus load was maintained when the challenge virus lacked the main latency-associated CD8+ T-cell epitope of M2, or when the vaccine virus lacked M2 entirely. This protection was maintained also when the vaccine virus lacked both episome maintenance and the genomic region encompassing M1, M2, M3, M4 and ORF4. Therefore, protection did not require immunity to known MuHV-4 latency genes. As the remaining vaccine virus genes have clear homologs in human γ-herpesviruses, this approach of deleting viral latency genes could also be applied to them, to generate safe and effective vaccines against human disease.
Assuntos
Infecções por Herpesviridae , Rhadinovirus/fisiologia , Vacinas Virais , Latência Viral/genética , Animais , Linhagem Celular , Cricetinae , Infecções por Herpesviridae/genética , Infecções por Herpesviridae/imunologia , Infecções por Herpesviridae/prevenção & controle , Camundongos , Camundongos Endogâmicos BALB C , Vacinas Virais/genética , Vacinas Virais/imunologia , Vacinas Virais/farmacologia , Latência Viral/imunologiaRESUMO
γδ T lymphocytes are commonly viewed as embracing properties of both adaptive and innate immunity. Contributing to this is their responsiveness to pathogen products, either with or without the involvement of the TCR and its coreceptors. This study clarifies this paradoxical behavior by showing that these two modes of responsiveness are the properties of two discrete sets of murine lymphoid γδ T cells. Thus, MyD88 deficiency severely impaired the response to malaria infection of CD27((-)), IL-17A-producing γδ T cells, but not of IFN-γ-producing γδ cells. Instead, the latter compartment was severely contracted by ablating CD27, which synergizes with TCRγδ in the induction of antiapoptotic mediators and cell cycle-promoting genes in CD27((+)), IFN-γ-secreting γδ T cells. Hence, innate versus adaptive receptors differentially control the peripheral pool sizes of discrete proinflammatory γδ T cell subsets during immune responses to infection.