Poxvirus A51R proteins regulate microtubule stability and antagonize a cell-intrinsic antiviral response.

Numerous viruses alter host microtubule (MT) networks during infection, but how and why they induce these changes is unclear in many cases. We show that the vaccinia virus (VV)-encoded A51R protein is a MT-associated protein (MAP) that directly binds MTs and stabilizes them by both promoting their growth and preventing their depolymerization. Furthermore, we demonstrate that A51R-MT interactions are conserved across A51R proteins from multiple poxvirus genera, and highly conserved, positively charged residues in A51R proteins mediate these interactions. Strikingly, we find that viruses encoding MT interaction-deficient A51R proteins fail to suppress a reactive oxygen species (ROS)-dependent antiviral response in macrophages that leads to a block in virion morphogenesis. Moreover, A51R-MT interactions are required for VV virulence in mice. Collectively, our data show that poxviral MAP-MT interactions overcome a cell-intrinsic antiviral ROS response in macrophages that would otherwise block virus morphogenesis and replication in animals.

FEAR antiviral response pathway is independent of interferons and countered by poxvirus proteins.

The human facilitates chromatin transcription (FACT) complex is a chromatin remodeller composed of human suppressor of Ty 16 homologue (hSpt16) and structure-specific recognition protein-1 subunits that regulates cellular gene expression. Whether FACT regulates host responses to infection remained unclear. We identify a FACT-mediated, interferon-independent, antiviral pathway that restricts poxvirus replication. Cell culture and bioinformatics approaches suggest that early viral gene expression triggers nuclear accumulation of SUMOylated hSpt16 subunits required for the expression of E26 transformation-specific sequence-1 (ETS-1)-a transcription factor that activates virus restriction programs. However, biochemical studies show that poxvirus-encoded A51R proteins block ETS-1 expression by outcompeting structure-specific recognition protein-1 binding to SUMOylated hSpt16 and by tethering SUMOylated hSpt16 to microtubules. Furthermore, A51R antagonism of FACT enhances poxvirus replication in human cells and virulence in mice. Finally, we show that FACT also restricts rhabdoviruses, flaviviruses and orthomyxoviruses, suggesting broad roles for FACT in antiviral immunity. Our study reveals the FACT-ETS-1 antiviral response (FEAR) pathway to be critical for eukaryotic antiviral immunity and describes a unique mechanism of viral immune evasion.

A visão do profissional enfermeiro sobre o tratamento da hanseníase na atenção básica / The nurse's view on Leprosy treatment in primary health care / La visión del profesional enfermero sobre el tratamiento de la lepra en la atención básica

Objetivo: Avaliar a visão dos enfermeiros atuantes na Atenção Básica (AB) sobre o tratamento da hanseníase. Métodos: Pesquisa do tipo descritiva, com abordagem qualitativa, realizada com nove enfermeiros que trabalham no município de Cocal, Piauí, Brasil, entre os meses de janeiro a março de 2016. A coleta de dados deu-se através de questões norteadoras sobre o tratamento da hanseníase e as respostas foram transcritas e ponderadas pela análise de conteúdo. Resultados: Os enfermeiros afirmaram que a poliquimioterapia é eficaz para o tratamento da hanseníase, assim como para a redução da carga da doença e cura do paciente. A supervisão está relacionada ao tratamento correto, garantia de cura, redução de sequelas e interrupção da transmissão da doença. A falha no tratamento está associada principalmente à falta do engajamento do paciente e da família, à ausência de medicação no posto de saúde, à carência de orientação ao paciente, ao baixo nível de escolaridade e aos efeitos colaterais dos remédios. A não adesão e o abandono do tratamento foram relacionados às complicações, como o agravamento de sintomas, as incapacidades e as amputações. Conclusão: O estudo mostrou que os enfermeiros avaliados possuíam conhecimento adequado sobre aspectos do tratamento da hanseníase na AB, evidenciando pontos que devem ser corrigidos para que se alcance excelência no combate à hanseníase, como a importância de incentivar a participação da família como coadjuvante no tratamento.

Objective: To evaluate Primary Health Care (PHC) nurses' view on leprosy treatment. Methods: Qualitative descriptive study conducted with nine nurses working in the municipality of Cocal, Piauí, Brazil, from January to March 2016. Data were collected using guiding questions about leprosy treatment and the answers were transcribed and submitted to content analysis. Results: The nurses stated that polychemotherapy is effective in the treatment of leprosy, as well as in reducing the burden of disease and curing the patient. Supervision is related to correct treatment, guarantee of cure, reduction of sequelae and interruption of disease transmission. Treatment failure is mainly associated with patient's and family's lack of engagement, lack of medication at the health clinic, lack of patient guidance, low levels of education, and drug side effects. Noncompliance with or cessation of treatment were related to complications such as aggravation of symptoms, disabilities, and amputations. Conclusion: The study showed that the nurses evaluated have adequate knowledge about aspects of leprosy treatment in PHC, highlighting points that must be corrected in order to achieve excellence in the fight against leprosy, such as the importance of encouraging family participation as a coadjutant in the treatment.

Objetivo: Evaluar la visión de los enfermeros que actúan en la Atención Básica (AB) sobre el tratamiento de la lepra. Métodos: Investigación del tipo descriptiva y de abordaje cualitativo realizada con nueve enfermeros que trabajan en el municipio de Cocal, Piauí, Brasil, entre los meses de enero y marzo de 2016. La recogida de datos se dio a través de cuestiones norteadoras sobre el tratamiento de la lepra y las respuestas fueron transcritas y analizadas a través del análisis de contenido. Resultados: Los enfermeros afirmaron que la poliquimioterapia es eficaz para el tratamiento de la lepra así como para la reducción de la carga de la enfermedad y la cura del enfermo. La supervisión relacionase al tratamiento correcto, la garantía de la cura, la reducción de las secuelas y la interrupción de la trasmisión de la enfermedad. La falla del tratamiento se asocia principalmente con la falta de compromiso del paciente y de la familia, la ausencia de la medicación en el centro de salud, la carencia de orientación al paciente, el bajo nivel de escolaridad y los efectos colaterales de los remedios. La no adhesión y el abandono del tratamiento se relacionaron con las complicaciones, el agravamiento de los síntomas, las incapacidades y las amputaciones. Conclusión: El estudio mostró que los enfermeros evaluados tenían el conocimiento adecuado de los aspectos del tratamiento de la lepra en la AB con evidencias de aspectos que deben ser corregidos para alcanzar la excelencia en el combate de la lepra como la importancia del incentivo a la participación de la familia como coadyuvante para el tratamiento.