ABSTRACT
Dengue, a mosquito-borne viral illness caused by dengue virus types (DENV)-1 to DENV-4, is endemic in Puerto Rico. Severe dengue usually occurs in individuals previously infected with DENV or among infants born to previously infected mothers. To describe clinical features of dengue in infants, we retrospectively characterized dengue patients aged < 18 months reported to the Passive Dengue Surveillance System (PDSS) during 1999-2011. To determine frequency of signs, symptoms, and disease severity, case report forms and medical records were evaluated for patients who tested positive for dengue by reverse transcriptase polymerase chain reaction or anti-DENV immunoglobulin Menzyme-linked immunosorbent assay. Of 4,178 reported patients aged < 18 months, 813 (19%) were laboratory positive. Of these, most had fever (92%), rash (53%), bleeding manifestations (52%), and thrombocytopenia (52%). Medical records were available for 145 (31%) of 472 hospitalized patients, of which 40% had dengue, 23% had dengue with warning signs, and 33% had severe dengue. Mean age of patients with severe dengue was 8 months. Anti-DENV immunoglobulin G (IgG) titers were not statistically different in patients with (50%) and without (59%) severe dengue. In this study, one-third of DENV-infected infants met the severe dengue case definition. The role of maternal anti-DENV IgG in development of severe disease warrants further study in prospective cohorts of mother-infant pairs.
Subject(s)
Dengue/epidemiology , Aging , Antibodies, Viral/blood , Female , Humans , Immunoglobulin G/blood , Infant , Male , Population Surveillance , Puerto Rico/epidemiologyABSTRACT
The Polycomb repressive complex 2 (PRC2) confers transcriptional repression through histone H3 lysine 27 trimethylation (H3K27me3). Here, we examined how PRC2 is modulated by histone modifications associated with transcriptionally active chromatin. We provide the molecular basis of histone H3 N terminus recognition by the PRC2 Nurf55-Su(z)12 submodule. Binding of H3 is lost if lysine 4 in H3 is trimethylated. We find that H3K4me3 inhibits PRC2 activity in an allosteric fashion assisted by the Su(z)12 C terminus. In addition to H3K4me3, PRC2 is inhibited by H3K36me2/3 (i.e., both H3K36me2 and H3K36me3). Direct PRC2 inhibition by H3K4me3 and H3K36me2/3 active marks is conserved in humans, mouse, and fly, rendering transcriptionally active chromatin refractory to PRC2 H3K27 trimethylation. While inhibition is present in plant PRC2, it can be modulated through exchange of the Su(z)12 subunit. Inhibition by active chromatin marks, coupled to stimulation by transcriptionally repressive H3K27me3, enables PRC2 to autonomously template repressive H3K27me3 without overwriting active chromatin domains.
