Differential effects of stress and African ancestry on preterm birth and related traits among US born and immigrant Black mothers.

Preterm birth (PTB, <37 weeks of gestation) is influenced by a wide range of environmental, genetic and psychosocial factors, and their interactions. However, the individual and joint effects of genetic factors and psychosocial stress on PTB have remained largely unexplored among U.S. born versus immigrant mothers.We studied 1121 African American women from the Boston Birth Cohort enrolled from 1998 to 2008. Regression-based analyses were performed to examine the individual and joint effects of genetic ancestry and stress (including lifetime stress [LS] and stress during pregnancy [PS]) on PTB and related traits among U.S. born and immigrant mothers.Significant associations between LS and PTB and related traits were found in the total study population and in immigrant mothers, including gestational age, birthweight, PTB, and spontaneous PTB; but no association was found in U.S. born mothers. Furthermore, significant joint associations of LS (or PS) and African ancestral proportion (AAP) on PTB were found in immigrant mothers, but not in U.S. born mothers.Although, overall, immigrant women had lower rates of PTB compared to U.S. born women, our study is one of the first to identify a subset of immigrant women could be at significantly increased risk of PTB and related outcomes if they have high AAP and are under high LS or PS. In light of the growing number of immigrant mothers in the U.S., our findings may have important clinical and public health implications.

An integrated approach to elucidate the intra-viral and viral-cellular protein interaction networks of a gamma-herpesvirus.

Genome-wide yeast two-hybrid (Y2H) screens were conducted to elucidate the molecular functions of open reading frames (ORFs) encoded by murine γ-herpesvirus 68 (MHV-68). A library of 84 MHV-68 genes and gene fragments was generated in a Gateway entry plasmid and transferred to Y2H vectors. All possible pair-wise interactions between viral proteins were tested in the Y2H assay, resulting in the identification of 23 intra-viral protein-protein interactions (PPIs). Seventy percent of the interactions between viral proteins were confirmed by co-immunoprecipitation experiments. To systematically investigate virus-cellular protein interactions, the MHV-68 Y2H constructs were screened against a cellular cDNA library, yielding 243 viral-cellular PPIs involving 197 distinct cellar proteins. Network analyses indicated that cellular proteins targeted by MHV-68 had more partners in the cellular PPI network and were located closer to each other than expected by chance. Taking advantage of this observation, we scored the cellular proteins based on their network distances from other MHV-68-interacting proteins and segregated them into high (Y2H-HP) and low priority/not-scored (Y2H-LP/NS) groups. Significantly more genes from Y2H-HP altered MHV-68 replication when their expression was inhibited with siRNAs (53% of genes from Y2H-HP, 21% of genes from Y2H-LP/NS, and 16% of genes randomly chosen from the human PPI network; p<0.05). Enriched Gene Ontology (GO) terms in the Y2H-HP group included regulation of apoptosis, protein kinase cascade, post-translational protein modification, transcription from RNA polymerase II promoter, and IκB kinase/NFκB cascade. Functional validation assays indicated that PCBP1, which interacted with MHV-68 ORF34, may be involved in regulating late virus gene expression in a manner consistent with the effects of its viral interacting partner. Our study integrated Y2H screening with multiple functional validation approaches to create γ-herpes viral-viral and viral-cellular protein interaction networks.