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Full-Text Articles in Organisms

Elucidating Immune Signaling Of Influenza A Virus And Aspergillus Fumigatus Co-Infections Through Pioneered Model Development, Meagan Danyelle Rippee-Brooks Aug 2019

Elucidating Immune Signaling Of Influenza A Virus And Aspergillus Fumigatus Co-Infections Through Pioneered Model Development, Meagan Danyelle Rippee-Brooks

MSU Graduate Theses

Bacterial co-infections with influenza A virus (IAV) are extremely serious and life-threatening. However, there exists limited understanding about the importance of fungal infections with IAV. Clinical case reports indicate that fungal co-infections do occur and suggest the IAV pandemic of 2009 had a propensity to predispose patients to secondary fungal infections more than previous IAV strains. IAV-fungal co-infections are marked by high mortality rates of 47 to 61% in previously healthy individuals between the ages of 20 and 60. Yet, the variables involved in this co-infection remain undetermined. I achieved effective recapitulation of this co-infection using a C57Bl/6 murine (mouse) …


Iiv-6 Inhibits Nf-Kappab Responses In Drosophila, Cara C. West, Florentina Rus, Ying Chen, Anni Kleino, Monique Gangloff, Don B. Gammon, Neal S. Silverman Jul 2019

Iiv-6 Inhibits Nf-Kappab Responses In Drosophila, Cara C. West, Florentina Rus, Ying Chen, Anni Kleino, Monique Gangloff, Don B. Gammon, Neal S. Silverman

Neal Silverman

The host immune response and virus-encoded immune evasion proteins pose constant, mutual selective pressure on each other. Virally encoded immune evasion proteins also indicate which host pathways must be inhibited to allow for viral replication. Here, we show that IIV-6 is capable of inhibiting the two Drosophila NF-kappaB signaling pathways, Imd and Toll. Antimicrobial peptide (AMP) gene induction downstream of either pathway is suppressed when cells infected with IIV-6 are also stimulated with Toll or Imd ligands. We find that cleavage of both Imd and Relish, as well as Relish nuclear translocation, three key points in Imd signal transduction, occur …


Control Of Antiviral Innate Immune Response By Protein Geranylgeranylation, Shigao Yang, Zhaozhao Jiang, Katherine A. Fitzgerald, Donghai Wang Jul 2019

Control Of Antiviral Innate Immune Response By Protein Geranylgeranylation, Shigao Yang, Zhaozhao Jiang, Katherine A. Fitzgerald, Donghai Wang

Katherine A. Fitzgerald

The mitochondrial antiviral signaling protein (MAVS) orchestrates host antiviral innate immune response to RNA virus infection. However, how MAVS signaling is controlled to eradicate virus while preventing self-destructive inflammation remains obscure. Here, we show that protein geranylgeranylation, a posttranslational lipid modification of proteins, limits MAVS-mediated immune signaling by targeting Rho family small guanosine triphosphatase Rac1 into the mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs) at the mitochondria-ER junction. Protein geranylgeranylation and subsequent palmitoylation promote Rac1 translocation into MAMs upon viral infection. MAM-localized Rac1 limits MAVS' interaction with E3 ligase Trim31 and hence inhibits MAVS ubiquitination, aggregation, and activation. Rac1 also facilitates …


A Multivalent Kaposi Sarcoma-Associated Herpesvirus-Like Particle Vaccine Capable Of Eliciting High Titers Of Neutralizing Antibodies In Immunized Rabbits, David H. Mulama, Lorraine Z. Mustvunguma, Jennifer Totonchy, Peng Ye, Joslyn Foley, Gabriela M. Escalante, Esther Rodriguez, Ramina Nabiee, Murali Muniraju, Felix Wussow, Anne K. Barasa, Javier Gordon Ogembo Jun 2019

A Multivalent Kaposi Sarcoma-Associated Herpesvirus-Like Particle Vaccine Capable Of Eliciting High Titers Of Neutralizing Antibodies In Immunized Rabbits, David H. Mulama, Lorraine Z. Mustvunguma, Jennifer Totonchy, Peng Ye, Joslyn Foley, Gabriela M. Escalante, Esther Rodriguez, Ramina Nabiee, Murali Muniraju, Felix Wussow, Anne K. Barasa, Javier Gordon Ogembo

Pharmacy Faculty Articles and Research

Kaposi sarcoma-associated herpesvirus (KSHV) is an emerging pathogen and the causative agent of multiple cancers in immunocompromised patients. To date, there is no licensed prophylactic KSHV vaccine. In this study, we generated a novel subunit vaccine that incorporates four key KSHV envelope glycoproteins required for viral entry in diverse cell types (gpK8.1, gB, and gH/gL) into a single multivalent KSHV-like particle (KSHV-LP). Purified KSHV-LPs were similar in size, shape, and morphology to KSHV virions. Vaccination of rabbits with adjuvanted KSHV-LPs generated strong glycoprotein-specific antibody responses, and purified immunoglobulins from KSHV-LP-immunized rabbits neutralized KSHV infection in epithelial, endothelial, fibroblast, and B …


The Association Between Herpes Simplex Virus Type 1 Reactivation And Alzheimer’S Disease, Andrew Allee May 2019

The Association Between Herpes Simplex Virus Type 1 Reactivation And Alzheimer’S Disease, Andrew Allee

BIO 410 Spring 2019 Research Papers

This review will focus on the interaction of herpes simplex virus type 1 (HSV-1) and its causative role in pathogenesis of Alzheimer’s disease (AD) noting specifically, the epidemiological relevance of addressing this problem, as well as the molecular pathways associated. HSV-1 reactivation tends to be one of the primary causative events that is responsible for many of the pathologies associated with AD, such as: amyloid beta (Aβ) accumulation caused by malfunctioning cleavage of amyloid precursor protein (APP) as well as tau hyperphosphorylation. HSV-1 reactivation is a primary causative event in downstream dysfunction and is also shown to be directed by …


Conformational Flexibility In The Enterovirus Rna Replication Platform, Meghan S. Warden, Kai Cai, Gabriel Cornilescu, Jordan E. Burke, Komala Ponniah, Samuel E. Butcher, Steven M. Pascal Jan 2019

Conformational Flexibility In The Enterovirus Rna Replication Platform, Meghan S. Warden, Kai Cai, Gabriel Cornilescu, Jordan E. Burke, Komala Ponniah, Samuel E. Butcher, Steven M. Pascal

Chemistry & Biochemistry Faculty Publications

A presumed RNA cloverleaf (5′CL), located at the 5′-most end of the noncoding region of the enterovirus genome, is the primary established site for initiation of genomic replication. Stem–loop B (SLB) and stem–loop D (SLD), the two largest stem–loops within the 5′CL, serve as recognition sites for protein interactions that are essential for replication. Here we present the solution structure of rhinovirus serotype 14 5′CL using a combination of nuclear magnetic resonance spectroscopy and small-angle X-ray scattering. In the absence of magnesium, the structure adopts an open, somewhat extended conformation. In the presence of magnesium, the structure compacts, bringing SLB …