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Immunology and Infectious Disease Commons™
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Articles 1 - 6 of 6
Full-Text Articles in Immunology and Infectious Disease
Caenorhabditis Elegans Micrornas Of The Let-7 Family Act In Innate Immune Response Circuits And Confer Robust Developmental Timing Against Pathogen Stress, Zhiji Ren, Victor R. Ambros
Caenorhabditis Elegans Micrornas Of The Let-7 Family Act In Innate Immune Response Circuits And Confer Robust Developmental Timing Against Pathogen Stress, Zhiji Ren, Victor R. Ambros
Victor R. Ambros
Animals maintain their developmental robustness against natural stresses through numerous regulatory mechanisms, including the posttranscriptional regulation of gene expression by microRNAs (miRNAs). Caenorhabditis elegans miRNAs of the let-7 family (let-7-Fam) function semiredundantly to confer robust stage specificity of cell fates in the hypodermal seam cell lineages. Here, we show reciprocal regulatory interactions between let-7-Fam miRNAs and the innate immune response pathway in C. elegans. Upon infection of C. elegans larvae with the opportunistic human pathogen Pseudomonas aeruginosa, the developmental timing defects of certain let-7-Fam miRNA mutants are enhanced. This enhancement is mediated by the p38 MAPK innate immune pathway acting …
Differential Expression Of Ape1 And Ape2 In Germinal Centers Promotes Error-Prone Repair And A:T Mutations During Somatic Hypermutation, Janet Stavnezer, Erin K. Linehan, Mikayla R. Thompson, Ghaith Habboub, Anna J. Ucher, Tatenda Kadungure, Daisuke Tsuchimoto, Yusaku Nakabeppu, Carol E. Schrader
Differential Expression Of Ape1 And Ape2 In Germinal Centers Promotes Error-Prone Repair And A:T Mutations During Somatic Hypermutation, Janet Stavnezer, Erin K. Linehan, Mikayla R. Thompson, Ghaith Habboub, Anna J. Ucher, Tatenda Kadungure, Daisuke Tsuchimoto, Yusaku Nakabeppu, Carol E. Schrader
Janet M. Stavnezer
Somatic hypermutation (SHM) of antibody variable region genes is initiated in germinal center B cells during an immune response by activation-induced cytidine deaminase (AID), which converts cytosines to uracils. During accurate repair in nonmutating cells, uracil is excised by uracil DNA glycosylase (UNG), leaving abasic sites that are incised by AP endonuclease (APE) to create single-strand breaks, and the correct nucleotide is reinserted by DNA polymerase beta. During SHM, for unknown reasons, repair is error prone. There are two APE homologs in mammals and, surprisingly, APE1, in contrast to its high expression in both resting and in vitro-activated splenic B …
Positive Selection Drives Preferred Segment Combinations During Influenza Virus Reassortment, Konstantin Zeldovich, Ping Liu, Nicholas Renzette, Matthieu Foll, Serena Pham, Sergey Venev, Glen Gallagher, Daniel Bolon, Evelyn Kurt-Jones, Jeffrey Jensen, Daniel Caffrey, Celia Schiffer, Timothy Kowalik, Jennifer Wang, Robert Finberg
Positive Selection Drives Preferred Segment Combinations During Influenza Virus Reassortment, Konstantin Zeldovich, Ping Liu, Nicholas Renzette, Matthieu Foll, Serena Pham, Sergey Venev, Glen Gallagher, Daniel Bolon, Evelyn Kurt-Jones, Jeffrey Jensen, Daniel Caffrey, Celia Schiffer, Timothy Kowalik, Jennifer Wang, Robert Finberg
Celia A. Schiffer
Influenza A virus (IAV) has a segmented genome that allows for the exchange of genome segments between different strains. This reassortment accelerates evolution by breaking linkage, helping IAV cross species barriers to potentially create highly virulent strains. Challenges associated with monitoring the process of reassortment in molecular detail have limited our understanding of its evolutionary implications. We applied a novel deep sequencing approach with quantitative analysis to assess the in vitro temporal evolution of genomic reassortment in IAV. The combination of H1N1 and H3N2 strains reproducibly generated a new H1N2 strain with the hemagglutinin and nucleoprotein segments originating from H1N1 …
The Genetics Of Hepatitis C Virus Underlie Its Ability To Escape Humoral Immunity, Jay Kolls, Gyongyi Szabo
The Genetics Of Hepatitis C Virus Underlie Its Ability To Escape Humoral Immunity, Jay Kolls, Gyongyi Szabo
Gyongyi Szabo
Hepatitis C virus (HCV) is a leading cause of chronic liver disease, and efforts to develop therapeutic vaccine strategies have been limited by immune escape due to HCV variants that are resistant to current vaccines or HCV variants that rapidly acquire new resistance-conferring mutations. Recently, the crystal structure of the viral envelope protein E2 region was resolved as well as how E2 docks to the host CD81 protein; therefore, antibodies that block this interaction should prevent viral entry into host cells. In this issue of the JCI, Bailey and colleagues show that immune escape of HCV can occur by naturally …
Exosomes From Hepatitis C Infected Patients Transmit Hcv Infection And Contain Replication Competent Viral Rna In Complex With Ago2-Mir122-Hsp90, Terence N. Bukong, Fatemeh Momen-Heravi, Karen Kodys, Shashi Bala, Gyongyi Szabo
Exosomes From Hepatitis C Infected Patients Transmit Hcv Infection And Contain Replication Competent Viral Rna In Complex With Ago2-Mir122-Hsp90, Terence N. Bukong, Fatemeh Momen-Heravi, Karen Kodys, Shashi Bala, Gyongyi Szabo
Gyongyi Szabo
Antibodies targeting receptor-mediated entry of HCV into hepatocytes confer limited therapeutic benefits. Evidence suggests that exosomes can transfer genetic materials between cells; however, their role in HCV infection remains obscure. Here, we show that exosomes isolated from sera of chronic HCV infected patients or supernatants of J6/JFH1-HCV-infected Huh7.5 cells contained HCV RNA. These exosomes could mediate viral receptor-independent transmission of HCV to hepatocytes. Negative sense HCV RNA, indicative of replication competent viral RNA, was present in exosomes of all HCV infected treatment non-responders and some treatment-naive individuals. Remarkably, HCV RNA was associated with Ago2, HSP90 and miR-122 in exosomes isolated …
Influenza Virus Drug Resistance: A Time-Sampled Population Genetics Perspective, Matthieu Foll, Yu Poh, Nicholas Renzette, Anna Admetlla, Claudia Bank, Hyunjin Shim, Anna Malaspinas, Gregory Ewing, Ping Liu, Daniel Wegmann, Daniel Caffrey, Konstantin Zeldovich, Daniel Bolon, Jennifer Wang, Timothy Kowalik, Celia Schiffer, Robert Finberg, Jeffrey Jensen
Influenza Virus Drug Resistance: A Time-Sampled Population Genetics Perspective, Matthieu Foll, Yu Poh, Nicholas Renzette, Anna Admetlla, Claudia Bank, Hyunjin Shim, Anna Malaspinas, Gregory Ewing, Ping Liu, Daniel Wegmann, Daniel Caffrey, Konstantin Zeldovich, Daniel Bolon, Jennifer Wang, Timothy Kowalik, Celia Schiffer, Robert Finberg, Jeffrey Jensen
Celia A. Schiffer
The challenge of distinguishing genetic drift from selection remains a central focus of population genetics. Time-sampled data may provide a powerful tool for distinguishing these processes, and we here propose approximate Bayesian, maximum likelihood, and analytical methods for the inference of demography and selection from time course data. Utilizing these novel statistical and computational tools, we evaluate whole-genome datasets of an influenza A H1N1 strain in the presence and absence of oseltamivir (an inhibitor of neuraminidase) collected at thirteen time points. Results reveal a striking consistency amongst the three estimation procedures developed, showing strongly increased selection pressure in the presence …