Peripheral blood MФ–cancer cell fusion hybrids identified in cancer patients correlate with disease stage and overall survival.

SignificanceThe evolutionary transformation from a blood-feeding to an obligate nonbiting lifestyle is occurring uniquely within the genetic background of a single species of mosquito, Wyeomyia smithii, as a product of selection in nature. Associated genetic changes in metabolic pathways indicate a high anticipatory metabolic investment prior to consuming blood, presumably balanced by the reproductive benefits from an imminent blood meal. This evolutionary transformation provides a starting point for determining pivotal upstream genetic changes between biters and nonbiters and for identifying universal nonbiting genes or pathways in mosquitoes. If there is no bite, there is no transmission of pathogens; hence W. smithii offers a different approach to investigate control of blood-feeding vectors of human diseases.

The response to respiratory viruses varies substantially between individuals, and there are currently no known molecular predictors from the early stages of infection. Here we conduct a community-based analysis to determine whether pre- or early post-exposure molecular factors could predict physiologic responses to viral exposure. Using peripheral blood gene expression profiles collected from healthy subjects prior to exposure to one of four respiratory viruses (H1N1, H3N2, Rhinovirus, and RSV), as well as up to 24 h following exposure, we find that it is possible to construct models predictive of symptomatic response using profiles even prior to viral exposure. Analysis of predictive gene features reveal little overlap among models; however, in aggregate, these genes are enriched for common pathways. Heme metabolism, the most significantly enriched pathway, is associated with a higher risk of developing symptoms following viral exposure. This study demonstrates that pre-exposure molecular predictors can be identified and improves our understanding of the mechanisms of response to respiratory viruses.