Project description:Influenza virus transmission between mothers and nursing-infants has not been investigated although mothers and infants often develop severe disease. Ferrets are considered the most appropriate model for influenza studies. We investigated influenza transmission in infant and nursing-mother ferrets. Influenza infected infants transmitted virus to mother mammary glands leading to live virus excretion in milk and influenza virus positive mammary gland epithelial cells. Global gene expression analysis showed down-regulation of milk production and induction of breast involution and oncogenesis pathways. Our results provide insight into influenza transmission between mothers and infants which may impact fields of infectious disease, maternal/infant health and neoplasm etiology.
Project description:Influenza virus transmission between mothers and nursing-infants has not been investigated although mothers and infants often develop severe disease. Ferrets are considered the most appropriate model for influenza studies. We investigated influenza transmission in infant and nursing-mother ferrets. Influenza infected infants transmitted virus to mother mammary glands leading to live virus excretion in milk and influenza virus positive mammary gland epithelial cells. Global gene expression analysis showed down-regulation of milk production and induction of breast involution and oncogenesis pathways. Our results provide insight into influenza transmission between mothers and infants which may impact fields of infectious disease, maternal/infant health and neoplasm etiology.
Project description:Infection with a single influenza A virus (IAV) is only rarely sufficient to initiate productive infection. Here, we exploit both single cell approaches and whole-animal systems to show that the extent of IAV reliance on multiple infection varies with virus strain and host species. Influenza A/guinea fowl/HK/WF10/99 (H9N2) [GFHK99] virus exhibits strong dependence on collective interactions in mammalian systems. This reliance focuses viral progeny production within coinfected cells and therefore results in frequent genetic exchange through reassortment. In contrast, GFHK99 virus has greatly reduced dependence on multiple infection in avian systems, indicating a role for host factors in viral collective interactions. Genetic mapping implicated the viral polymerase as a major driver of multiple infection dependence. Mechanistically, quantification of incomplete viral genomes showed that their complementation only partly accounts for the observed reliance on coinfection. Indeed, even when all polymerase components are detected in single cell mRNA sequencing, robust polymerase activity of GFHK99 virus in mammalian cells is reliant on multiple infection. In sum, IAV collective interactions not only augment reassortment, but can also overcome species-specific barriers to infection. These findings underscore the importance of virus-virus interactions in IAV infection, evolution and emergence. We used a single-cell sequencing platform (10x Genomics) to elucidate the differential infection rate of an avian influenza A virus on an avian cell line (DF1) and a mammalian (MDCK) cell line. Our work on IAV reassortment has raised new questions about the fundamental strategies that drive influenza virus evolution. Our data indicate that a large majority of influenza virus genomesare incomplete within cells, comprising less than the eight complete segments normally found in a replication competent infectious viral particle. This led us to ask: what underlying mechanisms give rise to incomplete genomes? What constitute an infectious unit? What are the implications for viral diversification, evolution and spread. By addressing these questions, we will advance he field by deepening our understanding how viral infections are initiated and propagated.
Project description:Influenza virus transmission between mothers and nursing-infants has not been investigated although mothers and infants often develop severe disease. Ferrets are considered the most appropriate model for influenza studies. We investigated influenza transmission in infant and nursing-mother ferrets. Influenza infected infants transmitted virus to mother mammary glands leading to live virus excretion in milk and influenza virus positive mammary gland epithelial cells. Global gene expression analysis showed down-regulation of milk production and induction of breast involution and oncogenesis pathways. Our results provide insight into influenza transmission between mothers and infants which may impact fields of infectious disease, maternal/infant health and neoplasm etiology. Total RNA was obtained from nursing mother ferret mammary glands at days 3/4 and 6/7 post-intranasal kit infection with 10^5 EID50 A/California/07/2009 (H1N1). Total RNA was also collected from uninfected control nursing mother mammary gland tissues (n = 3). Changes in gene expression relative to uninfected tissue controls were then investigated.
Project description:Influenza virus transmission between mothers and nursing-infants has not been investigated although mothers and infants often develop severe disease. Ferrets are considered the most appropriate model for influenza studies. We investigated influenza transmission in infant and nursing-mother ferrets. Influenza infected infants transmitted virus to mother mammary glands leading to live virus excretion in milk and influenza virus positive mammary gland epithelial cells. Global gene expression analysis showed down-regulation of milk production and induction of breast involution and oncogenesis pathways. Our results provide insight into influenza transmission between mothers and infants which may impact fields of infectious disease, maternal/infant health and neoplasm etiology. Total RNA was obtained from ferret lungs at days 3 and 6 post-intranasal infection with 10^5 EID50 A/California/07/2009 (H1N1) (n = 3/time-point). Total RNA was also collected from uninfected control lung tissues (n = 3). Changes in gene expression relative to uninfected tissue controls were then investigated.
Project description:Influenza virus infection leads to global cardiac proteome remodeling during convalescence MTD project_description "Influenza virus infections lead to more than 500,000 hospitalizations in the U.S. every year. Patients with cardiovascular diseases have been shown to be at high risk of influenza mediated cardiac complications. Importantly, recent reports have provided clinical data supporting a direct link between laboratory-confirmed influenza virus infection and adverse cardiac events. However, the molecular mechanisms of how influenza virus infection induces detrimental cardiac changes, even after resolution of the pulmonary infection, is completely unknown.
Project description:Influenza virus infection leads to global cardiac proteome remodeling during convalescence MTD project_description "Influenza virus infections lead to more than 500,000 hospitalizations in the U.S. every year. Patients with cardiovascular diseases have been shown to be at high risk of influenza mediated cardiac complications. Importantly, recent reports have provided clinical data supporting a direct link between laboratory-confirmed influenza virus infection and adverse cardiac events. However, the molecular mechanisms of how influenza virus infection induces detrimental cardiac changes, even after resolution of the pulmonary infection, is completely unknown. We performed global quantitative proteomics as well as phosphoproteomics in this study.
Project description:Influenza virus infection leads to global cardiac proteome remodeling during convalescence MTD project_description "Influenza virus infections lead to more than 500,000 hospitalizations in the U.S. every year. Patients with cardiovascular diseases have been shown to be at high risk of influenza mediated cardiac complications. Importantly, recent reports have provided clinical data supporting a direct link between laboratory-confirmed influenza virus infection and adverse cardiac events. However, the molecular mechanisms of how influenza virus infection induces detrimental cardiac changes, even after resolution of the pulmonary infection, is completely unknown. Mixed lineage kinase domain-like protein (MLKL) is a pseudokinas that mediates necroptosis. We performed global quantitative proteomics as well as phosphoproteomics to understand its role in the heart in response to inflenza virus infection in this study.