Epigenetic reprogramming around IFN1 and IFNy2 promoters in rainbow trout cells inoculated with infectious pancreatic necrosis virus (IPNV)

12 Pág.Infectious pancreatic necrosis virus (IPNV) has proven to effectively evade the host antiviral responses. This study clarifies whether the modulation of the antiviral immune response exerted by IPNV involves epigenetic mechanisms. An in-silico characterization of the rainbow trout IFN1 and IFNγ2 promoters was performed, identifying the islands or sequences rich in CpG dinucleotides and the putative transcription factor binding sites (TBS) for both gene promoters. RTS11 cells (rainbow trout monocyte/macrophage) were infected with IPNV, and the course of viral infection was followed up to 48 h post infection (hpi). Infected cells showed increased IFN1 and IFNγ2 transcriptional expression at 6 and 24 hpi, respectively. IPNV infection caused increases and decreases in global IFNγ2 promoter methylation at 6 and 24 hpi, respectively. The CpG dinucleotides at positions -392 and + 38 of this promoter were the most sensitive to methylation changes. The IFN1 promoter remained fully unmethylated during the course of the infection, similar to the control. The changes in the methylation pattern observed for the IFNγ2 promoter were coincident with the changes in DNA methyltransferase (DNMT) expression levels, increasing at 6 hpi and decreasing below basal level at 24 hpi. Similarly, the H4 histones associated with the IFN1 and IFNγ2 promoters were hyperacetylated at 6 hpi, subsequently decreasing their acetylation below basal levels at 24 hpi, in both promoters. Coincidentally with the above, overexpression of histone acetyltransferase (HAT) was observed at 6 hpi and of histone deacetylase (HDAC) at 24 hpi, with return to baseline of HAT. These results suggest that IPNV would epigenetically modulate the expression of IFN1 by changing acetylation levels of the histones H4 associated with its promoter. Also, the modulation of the expression of IFNy2 would be by switching methylation/demethylation levels of its promoter, in addition to changes in acetylation levels of histones H4 associated with this promoter. This study is the first to demonstrate the effect of epigenetic reprogramming after IPNV infection in salmonid cells, demonstrating that promoter methylation/demethylation level and changes in the histone code associated with promoters may play a role in the modulation of the immune response induced by the virus.These studies were supported by the Fondo Nacional de Desarrollo Científico y Tecnológico de Chile [FONDECYT grants 1150934 and 3170881 ], Fondo de Fomento al Desarrollo Científico y Tecnológico [FONDEF D08I1096 ], and Fondo de Financiamiento de Centros de Investigación en Áreas Prioritarias [FONDAP grants 15110027 and 1522A0004 ], from Agencia Nacional de Investigación y Desarrollo (ANID) from the Chilean Government.Peer reviewe

Trends in Infant mortality rate and mortality for neonates born at less than 32 weeks and with very low birth weight

The aim of the study was to assess the trend of the infant mortality rate between 1990-2004 and the neonatal mortality between 2000-2005 in infants born at less than 32 weeks of gestational age or with very low birth-weight. Based on secondary data, infant mortality rate and by its component for Valdivia city were compared with national indicators. Mortality at Para evaluar la tendencia de la mortalidad infantil entre 1990-2004 y la mortalidad de prematuros menores de 32 semanas de edad de gestación y niños de muy bajo peso al nacer, entre 2000-2005, se compararon los datos secundarios globales por componentes del Servicio de Salud Valdivia con los totales del país, en Chile. Se calculó la mortalidad específica, por mil nacidos vivos, para los Para avaliar a tendência da mortalidade infantil, entre 1990 e 2004, a mortalidade de prematuros <32 semanas de idade gestacional e crianças de muito baixo peso ao nascer, entre 2000 e 2005, compararam-se dados secundários globais e por componentes do Serviço de Saúde Valdivia, e do total do país (Chile). Calculou-se a mortalidade específica em <32 semanas e <1.500g, por mil nascidos vivos, estabelecendo causas de óbito e avaliando sua relação com intervenções específicas, como uso de surfactante e corticoides pré-natais. A mortalidade infantil deteve sua queda a partir do ano 2000, com referência à década precedente, e a brecha que existia, entre os valores nacionais e locais antes de 2000, reduziu drasticamente. A mortalidade em <32 semanas e <1.500g variou entre 88 e 200‰ nascidos vivos, destacando a síndrome da angústia respiratória como principal causa de morte. O uso de corticoides e surfactante coincidiu com reduções da mortalidade