Virology Commons^™

Viral Infection: An Evolving Insight Into The Signal Transduction Pathways Responsible For The Innate Immune Response, Girish J. Kotwal, Steven Hatch, William L. Marshall

Open Access Articles

The innate immune response is initiated by the interaction of stereotypical pathogen components with genetically conserved receptors for extracytosolic pathogen-associated molecular patterns (PAMPs) or intracytosolic nucleic acids. In multicellular organisms, this interaction typically clusters signal transduction molecules and leads to their activations, thereby initiating signals that activate innate immune effector mechanisms to protect the host. In some cases programmed cell death-a fundamental form of innate immunity-is initiated in response to genotoxic or biochemical stress that is associated with viral infection. In this paper we will summarize innate immune mechanisms that are relevant to viral pathogenesis and outline the continuing evolution ...

Host-Pathogen Interactions Of Retroviruses, Abdul A. Waheed, Abraham L. Brass, Suryaram Gummuluru, Gilda Tachedjian

Open Access Articles

No abstract provided.

Herv-H Rna Is Abundant In Human Embryonic Stem Cells And A Precise Marker For Pluripotency, Federico A. Santoni, Jessica Guerra, Jeremy Luban

Open Access Articles

BACKGROUND: Certain post-translational modifications to histones, including H3K4me3, as well as binding sites for the transcription factor STAT1, predict the site of integration of exogenous gamma-retroviruses with great accuracy and cell-type specificity. Statistical methods that were used to identify chromatin features that predict exogenous gamma-retrovirus integration site selection were exploited here to determine whether cell type-specific chromatin markers are enriched in the vicinity of endogenous retroviruses (ERVs).

RESULTS: Among retro-elements in the human genome, the gamma-retrovirus HERV-H was highly associated with H3K4me3, though this association was only observed in embryonic stem (ES) cells (p < 10-300) and, to a lesser extent, in induced pluripotent stem (iPS) cells. No significant association was observed in nearly 40 differentiated cell types, nor was any association observed with other retro-elements. Similar strong association was observed between HERV-H and the binding sites within ES cells for the pluripotency transcription factors NANOG, OCT4, and SOX2. NANOG binding sites were located within the HERV-H 5'LTR itself. OCT4 and SOX2 binding sites were within 1 kB and 2 kB of the 5'LTR, respectively. In keeping with these observations, HERV-H RNA constituted 2% of all poly A RNA in ES cells. As ES cells progressed down a differentiation pathway, the levels of HERV-H RNA decreased progressively. RNA-Seq datasets showed HERV-H transcripts to be over 5 kB in length and to have the structure 5'LTR-gag-pro-3'LTR, with no evidence of splicing and no intact open reading frames.

CONCLUSION: The developmental regulation of HERV-H ...

Improving Oncolytic Vesicular Stomatitis Virus Through Modulation Of The Anti-Tumour Immune Response, Kyle B. Stephenson

Open Access Dissertations and Theses

Despite improvements in detection and treatment, cancer is the leading cause of death worldwide. Current treatment modalities have not been able to improve the mortality rates and significant toxicities limit efficacy. Therefore there is a need for development of novel therapeutics.

Oncolytic viruses have the ability to efficiently replicate in and destroy tumours while leaving normal tissues unharmed. These treatment platforms have been gaining momentum in recent years due to pre-clinical and clinical successes. Oncolytic viruses are extremely safe with limited toxicity observed in phase I/II clinical trials, and objective responses have been observed in some patients treated with ...

Telomere-Related Factors And Human Papillomavirus Genome Maintenance, Adam Rogers

Dissertations and Theses in Biological Sciences

Human papillomaviruses (HPVs) are small DNA tumor viruses identified by their characteristic ability to replicate as a nuclear plasmid in mitotically active basal keratinocytes. A key characteristic of the HPV life cycle is the establishment of a stable maintenance phase wherein the virus replicates at low copy number, which likely occurs in cells expressing little to no E1 and E2. It is thought that HPV16 replicates in a once-per-cell-cycle manner during this portion of its life cycle and presumably interacts with host chromosome replication and maintenance factors to facilitate this replication. The adaptive radiation of papillomaviruses in response to changing ...

Evolution Of Human Immunodeficiency Virus Type 1 Clade C Envelope V1-V5 Region During Disease Progression In Non-Human Primate Model, For Yue Tso

Dissertations and Theses in Biological Sciences

Human immunodeficiency virus type 1 (HIV-1) clade C strain is the fastest spreading HIV-1 strain globally, especially in Africa. It has been decades since the acquired immune deficiency syndrome (AIDS) pandemic first started. However, an effective anti-HIV-1 vaccine is not yet available, which is partly due to the highly variable nature of HIV-1 envelope gene and the absence of a suitable animal model. Strengthening of the understanding of envelope evolution during disease progression will contribute significantly towards future anti-HIV-1 treatment and preventions.
Non-human primates have been an essential animal model for many biomedical research areas. Using simian-human immunodeficiency virus (SHIV ...

Dengue Viral Rna Levels In Peripheral Blood Mononuclear Cells Are Associated With Disease Severity And Preexisting Dengue Immune Status, Anon Srikiatkhachorn, Sineewanlaya Wichit, Robert V. Gibbons, Sharone Green, Daniel H. Libraty, Timothy P. Endy, Francis A. Ennis, Siripen Kalayanarooj, Alan L. Rothman

Open Access Articles

BACKGROUND: Infection with dengue viruses (DENV) causes a wide range of manifestations from asymptomatic infection to a febrile illness called dengue fever (DF), to dengue hemorrhagic fever (DHF). The in vivo targets of DENV and the relation between the viral burden in these cells and disease severity are not known.

METHOD: The levels of positive and negative strand viral RNA in peripheral blood monocytes, T/NK cells, and B cells and in plasma of DF and DHF cases were measured by quantitative RT-PCR.

RESULTS: Positive strand viral RNA was detected in monocytes, T/NK cells and B cells with the ...

Cd200r1 Supports Hsv-1 Viral Replication And Licenses Pro-Inflammatory Signaling Functions Of Tlr2, Roy J. Soberman, Christopher R. Mackay, Christine A. Vaine, Glennice Bowen Ryan, Anna M. Cerny, Mikayla R. Thompson, Boris Nikolic, Valeria Primo, Peter Christmas, Paul Sheiffele, Lisa Aronov, David M. Knipe, Evelyn A. Kurt-Jones

GSBS Student Publications

The CD200R1:CD200 axis is traditionally considered to limit tissue inflammation by down-regulating pro-inflammatory signaling in myeloid cells bearing the receptor. We generated CD200R1(-/-) mice and employed them to explore both the role of CD200R1 in regulating macrophage signaling via TLR2 as well as the host response to an in vivo, TLR2-dependent model, herpes simplex virus 1 (HSV-1) infection. CD200R1(-/-) peritoneal macrophages demonstrated a 70-75% decrease in the generation of IL-6 and CCL5 (Rantes) in response to the TLR2 agonist Pam(2)CSK(4) and to HSV-1. CD200R1(-/-) macrophages could neither up-regulate the expression of TLR2, nor assemble a functional ...

Transcriptional Analysis Of Cervical Epithelial Cell Responses To Hiv-1, Andrew A. Block

Dissertations and Theses in Biological Sciences

Human Immunodeficiency Virus type 1 (HIV-1) infection causes a growing pandemic throughout the world, of which women comprise 51% of people who live with HIV-1, more than 60% in sub-Saharan Africa. HIV-1 infections of women are mainly acquired through female reproductive tract where cervical and vaginal epithelial cells are the first line of defense. Although HIV-1 does not directly infect epithelial cells, HIV-1 obligatorily interacts with and crosses over epithelial layer to infect susceptible target cells, mainly CD4+ T cells, in the lamina propria to initiate an infection. However, the mechanism and ramification of the interaction of HIV-1 and epithelial ...

Structure-Function Analysis Of A Protein Encoded By The Bhv-1 Latency Related Gene, Devis Sinani

Dissertations & Theses in Veterinary and Biomedical Science

Bovine herpes virus 1 (BHV-1) is a significant viral pathogen in cattle that induces a myriad of clinical symptoms. These symptoms include: conjunctivitis, upper respiratory tract infections, genital disorders, and abortions. BHV-1 infection can also lead to transient immune-suppression, which predisposes cattle to secondary bacterial infection leading to life-threatening pneumonia referred to as bovine respiratory disease (BRD). Following acute infection, BHV-1 establishes latency in sensory neurons within trigeminal ganglia. Reactivation of the virus can occur periodically, resulting in virus transmission. The latency-related (LR) RNA is the only abundantly expressed transcript in latently infected sensory neurons and it encodes several proteins ...

Characterization Of Binding And Fusion Efficiencies Mediated By The V1-V5 Env Derived From Transmitted And Non-Transmitted Viruses Isolated From A Perinatal Transmission Cohort From Zambia, Mackenzie Waltke

Dissertations and Theses in Biological Sciences

Human Immunodeficiency Virus Type 1 (HIV-1) is the etiological agent of acquired immunodeficiency syndrome (AIDS), which affects over 34 million people worldwide. In sub-Saharan Africa where access to antiretroviral therapies (ART) is limited, mother-to-child transmission (MTCT) rates remain high and represent a major concern in the global HIV/AIDS epidemic. Little is known about the biological properties of viruses that are transmitted perinatally, including how the biological functions of envelope (Env) influence transmissibility. Previously, transmitted viruses were found to have an advantage in replicative fitness mediated by Env V1-V5. In this study viruses derived from transmitting mother infant pairs (MIPs ...

Aspects Of Human Rhinovirus Infection In Hospitalized And Non-Hospitalized Individuals, Andrea C. Granados

Open Access Dissertations and Theses

Human rhinovirus (HRV) is a single-stranded RNA virus responsible for causing the common cold and exacerbating chronic respiratory diseases. HRV is the most common cause of acute respiratory illness. Unfortunately, difficult culturing conditions and perceived mild symptoms have limited our understanding of HRV. This thesis characterizes fundamental aspects of HRV such as viral load in different patient populations, prevalence and diversity of HRV, and severity and duration of infection.

We developed an HRV qPCR assay to quantitate HRV in clinical isolates. We used this assay to measure viral loads in hospitalized and community members. We found that HRV viral loads ...

Strategies To Characterize Functional Regions Of The Varicella-Zoster Virus Encapsidation Proteins, Pearl C. Pfiester

Master's Theses

Varicella-zoster virus (VZV) is a double-stranded DNA virus that causes a self-limiting primary infection known as chickenpox and can manifest into a painful, debilitating disease known as shingles in its latent form. Current therapies target the DNA replication process, but novel studies propose targeting the encapsidation process of VZV. The encapsidation process of VZV is based on the well-studied Herpes Simplex 1 (HSV-1) homologs. Seven genes or open reading frames (ORFs) are experimentally shown to be essential for HSV-1 DNA encapsidation. This thesis explores two specific strategies to characterize functional regions of the VZV encapsidation proteins: 1) stable cell lines ...