Systems-Biology Approaches to Discover Anti-Viral Effectors of the Human Innate Immune Response

Virus infections elicit an immediate innate response involving antiviral factors. The activities of some of these factors are, in turn, blocked by viral countermeasures. The ensuing battle between the host and the viruses is crucial for determining whether the virus establishes a foothold and/or induces adaptive immune responses. A comprehensive systems-level understanding of the repertoire of anti-viral effectors in the context of these immediate virus-host responses would provide significant advantages in devising novel strategies to interfere with the initial establishment of infections. Recent efforts to identify cellular factors in a comprehensive and unbiased manner, using genome-wide siRNA screens and other systems biology “omics” methodologies, have revealed several potential anti-viral effectors for viruses like Human immunodeficiency virus type 1 (HIV-1), Hepatitis C virus (HCV), West Nile virus (WNV), and influenza virus. This review describes the discovery of novel viral restriction factors and discusses how the integration of different methods in systems biology can be used to more comprehensively identify the intimate interactions of viruses and the cellular innate resistance

Parity modulates impact of BMI and gestational weight gain on gut microbiota in human pregnancy

ABSTRACTDysregulation of maternal adaptations to pregnancy due to high pre-pregnancy BMI (pBMI) or excess gestational weight gain (GWG) is associated with worsened health outcomes for mothers and children. Whether the gut microbiome contributes to these adaptations is unclear. We longitudinally investigated the impact of pBMI and GWG on the pregnant gut microbiome. We show that the gut microbiota of participants with higher pBMI changed less over the course of pregnancy in primiparous but not multiparous participants. This suggests that previous pregnancies may have persistent impacts on maternal adaptations to pregnancy. This ecological memory appears to be passed on to the next generation, as parity modulated the impact of maternal GWG on the infant gut microbiome. This work supports a role of the gut microbiome in maternal adaptations to pregnancy and highlights the need for longitudinal sampling and accounting for parity as key considerations for studies of the microbiome in pregnancy and infants. Understanding how these factors contribute to and shape maternal health is essential for the development of interventions impacting the microbiome, including pre/probiotics