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Articles 1081 - 1110 of 1476

Full-Text Articles in Microbiology

Coronavirus Replicase Proteins: Multifunctional Mediators Of Replication And Innate Immunity Evasion, Mark Anthony Clementz Jan 2010

Coronavirus Replicase Proteins: Multifunctional Mediators Of Replication And Innate Immunity Evasion, Mark Anthony Clementz

Dissertations

Coronaviruses are positive-sense, single-stranded RNA viruses. The majority of the RNA encodes non-structural proteins (nsps) that are translated as a large polyprotein, which is cleaved by the papain-like (PLP) and picornavirus 3C-like (3CLpro) proteases. The nsps modify host membranes to produce double membrane vesicles (DMVs) upon which the replicase-transcriptase assembles and synthesizes viral RNA. nsp3, nsp4, and nsp6 are integral membrane proteins believed to be involved in DMV formation. Work presented here demonstrates that nsp4 is subjected to N-linked glycosylation and mutation of N258 to threonine in nsp4 confers a temperature sensitive phenotype to MHV-A59 infectious clone virus. This virus …


The Immune Response In The Central Nervous System During West Nile Virus Persistence, Barbara Sharon Stewart Jan 2010

The Immune Response In The Central Nervous System During West Nile Virus Persistence, Barbara Sharon Stewart

Legacy Theses & Dissertations (2009 - 2024)

West Nile virus (WNV) persists in a wide array of hosts ranging from mice to humans. In convalescent humans, WNV RNA persists in urine for up to 6.7 years, and IgM antibody against WNV persists in serum for up to 12 months post-inoculation (p.i.). Previous work using the mouse model demonstrated that WNV persists in central nervous system (CNS) tissues as infectious virus and as RNA for up to 4 months and 6 months p.i., respectively. In this study, we sought to elucidate the mechanism for viral persistence in the CNS using the mouse model. Characterization of the leukocyte infiltrate …


Chlorella Viruses Encode Most, If Not All, Of The Machinery To Glycosylate Their Glycoproteins Independent Of The Endoplasmic Reticulum And Golgi, James L. Van Etten, James Gurnon, Giane M. Yanai-Balser, David Dunigan, Michael V. Graves Jan 2010

Chlorella Viruses Encode Most, If Not All, Of The Machinery To Glycosylate Their Glycoproteins Independent Of The Endoplasmic Reticulum And Golgi, James L. Van Etten, James Gurnon, Giane M. Yanai-Balser, David Dunigan, Michael V. Graves

Nebraska Center for Virology: Faculty Publications

In contrast to all other viruses that use the host machinery located in the endoplasmic reticulum and Golgi to glycosylate their glycoproteins, the large dsDNA-containing chlorella viruses encode most, if not all, of the components to glycosylate their major capsid proteins. Furthermore, all experimental results indicate that glycosylation occurs independent of the endoplasmic reticulum and Golgi. (Review article)


Interactions Of The Cellular Sumoylation System With Influenza A Virus And Its Non-Structural Protein Ns1a (Ns1a), Sangita Pal Jan 2010

Interactions Of The Cellular Sumoylation System With Influenza A Virus And Its Non-Structural Protein Ns1a (Ns1a), Sangita Pal

Open Access Theses & Dissertations

The most important current anti-influenza weapons, vaccination and antiviral drugs, can be rapidly rendered fully ineffective thanks to the virus's high mutational rate, which produces viruses exhibiting new antigenic properties and structural proteins insensitive to the drug's mechanism of action. One attractive alternative is to develop drugs that modulate the activity of cellular systems either required for viral growth or able to neutralize viral growth. Here we demonstrate that the cellular SUMOylation system, a post-translational modification involving the conjugation of the Small Ubiquitin-like MOdifier (SUMO) to specific protein targets using a Ubiquitin-like enzymatic cascade, interacts closely with influenza virus during …


The Role Of Sumoylation Of Ledgf/P75 In Hiv-1 Infection, Murilo Tadeu Domingues Bueno Jan 2010

The Role Of Sumoylation Of Ledgf/P75 In Hiv-1 Infection, Murilo Tadeu Domingues Bueno

Open Access Theses & Dissertations

The lens epithelium-derived growth factor (LEDGF) proteins p75 and p52 are transcriptional co-activators that protect cells from stresses through modulation of stress and heat shock-related genes. Besides regulating such genes, LEDGF/p75 is also important in the process of HOX gene expression and leukemia transformation driven by the MLL histone methyl transferase complex. By exploiting a similar mechanism of interaction between LEDGF/p75 and MLL, the HIV-1 viral protein Integrase (IN) associates with LEDGF/p75 in order to execute efficient viral DNA integration. This present work has identified that LEDGF proteins are posttranslationally modified by SUMO-1 and -3. SUMOylation was found to target …


Short Communication: Antiretroviral Therapy Resistance Mutations Present In The Hiv Type 1 Subtype C Pol And Env Regions From Therapy-Naive Patients In Zambia, Sandra Gonzalez, Clement Gondwe, Damien C. Tully, Veenu Minhas, Danielle Shea, Chipepo Kankasa, Tendai M'Soka, Charles Wood Jan 2010

Short Communication: Antiretroviral Therapy Resistance Mutations Present In The Hiv Type 1 Subtype C Pol And Env Regions From Therapy-Naive Patients In Zambia, Sandra Gonzalez, Clement Gondwe, Damien C. Tully, Veenu Minhas, Danielle Shea, Chipepo Kankasa, Tendai M'Soka, Charles Wood

Nebraska Center for Virology: Faculty Publications

The prevalence of antiretroviral therapy (ART) resistance mutations present in HIV-1 subtype C pol and env regions of the proviral DNA was analyzed and compared from therapy-naive individuals before (Cohort A) and after (Cohort B) the availability of free ART in Zambia. Mutations present in sequences published in a previous study from Zambian ART-naive individuals infected with subtype C were analyzed using current parameters for the classification of ART drug resistance and compared with Cohorts A and B. No statistically significant differences were observed when comparing mutations present in the pol and env of these cohorts. However, an increase in …


Primary Gamma-Herpesviral Infection In Zambian Children, Veenu Minhas, Brad P. Brayfield, Kay L. Crabtree, Chipepo Kankasa, Charles D. Mitchell, Charles Wood Jan 2010

Primary Gamma-Herpesviral Infection In Zambian Children, Veenu Minhas, Brad P. Brayfield, Kay L. Crabtree, Chipepo Kankasa, Charles D. Mitchell, Charles Wood

Nebraska Center for Virology: Faculty Publications

Background: HHV-8 is closely related to Epstein-Barr virus (EBV), but the clinical presentations of these two infections in early childhood are not well understood. Also, it is not known whether infection by one virus correlates with another. Here, we compare the natural history of infection by these two viruses along with the clinical manifestations and risk factors that are associated with early childhood infection in Zambia, which is an endemic area for HHV-8.

Methods: This study was conducted in a cohort of 12 month old Zambian children (N = 677). Data on socio-economic status and a wide range …


Restricted Genetic Diversity Of Hiv-1 Subtype C Envelope Glycoprotein From Perinatally Infected Zambian Infants, Hong Zhang, Damien C. Tully, Federico G. Hoffmann, Jun He, Chipepo Kankasa, Charles Wood Jan 2010

Restricted Genetic Diversity Of Hiv-1 Subtype C Envelope Glycoprotein From Perinatally Infected Zambian Infants, Hong Zhang, Damien C. Tully, Federico G. Hoffmann, Jun He, Chipepo Kankasa, Charles Wood

Nebraska Center for Virology: Faculty Publications

Background: Mother-to-child transmission of HIV-1 remains a significant problem in the resource-constrained settings where anti-retroviral therapy is still not widely available. Understanding the earliest events during HIV-1 transmission and characterizing the newly transmitted or founder virus is central to intervention efforts. In this study, we analyzed the viral env quasispecies of six mother-infant transmission pairs (MIPs) and characterized the genetic features of envelope glycoprotein that could influence HIV-1 subtype C perinatal transmission.

Methodology and Findings: The V1-V5 region of env was amplified from 6 MIPs baseline samples and 334 DNA sequences in total were analyzed. A comparison of …


Subtype-Associated Differences In Hiv-1 Reverse Transcription Affect The Viral Replication, Sergey Iordanskiy, Mackenzie Waltke, Yanjun Feng, Charles Wood Jan 2010

Subtype-Associated Differences In Hiv-1 Reverse Transcription Affect The Viral Replication, Sergey Iordanskiy, Mackenzie Waltke, Yanjun Feng, Charles Wood

Nebraska Center for Virology: Faculty Publications

Background: The impact of the products of the pol gene, specifically, reverse transcriptase (RT) on HIV-1 replication, evolution, and acquisition of drug resistance has been thoroughly characterized for subtype B. For subtype C, which accounts of almost 60% of HIV cases worldwide, much less is known. It has been reported that subtype C HIV-1 isolates have a lower replication capacity than B; however, the basis of these differences remains unclear.

Results: We analyzed the impact of the pol gene products from HIV-1 B and C subtypes on the maturation of HIV virions, accumulation of reverse transcription products, integration …


Topological Layers In The Hiv-1 Gp120 Inner Domain Regulate Gp41 Interaction And Cd4-Triggered Conformational Transitions, Andrés Finzi, Shi-Hua Xiang, Beatriz Pacheco, Dana-Farber Cancer Institute Wang, Jessica Haight, Aemro Kassa, Brenda Danek, Marie Pancera, Peter D. Kwong, Joseph Sodroski Jan 2010

Topological Layers In The Hiv-1 Gp120 Inner Domain Regulate Gp41 Interaction And Cd4-Triggered Conformational Transitions, Andrés Finzi, Shi-Hua Xiang, Beatriz Pacheco, Dana-Farber Cancer Institute Wang, Jessica Haight, Aemro Kassa, Brenda Danek, Marie Pancera, Peter D. Kwong, Joseph Sodroski

Nebraska Center for Virology: Faculty Publications

The entry of human immunodeficiency virus (HIV-1) into cells is initiated by binding of the gp120 exterior envelope glycoprotein to the receptor, CD4. How does CD4 binding trigger conformational changes in gp120 that allow the gp41 transmembrane envelope glycoprotein to mediate viral-cell membrane fusion? The transition from the unliganded to the CD4-bound state is regulated by two potentially flexible topological layers (layers 1 and 2) in the gp120 inner domain. Both layers apparently contribute to the noncovalent association of unliganded gp120 with gp41. After CD4 makes initial contact with the gp120 outer domain, layer 1-layer 2 interactions strengthen gp120-CD4 binding …


Neuroaids In Africa, Kevin Robertson, Jeff Liner, James Hakim, Jean-Louis Sankalé, Igor Grant, Scott Letendre, David Clifford, Amadou Gallo Diop, Assan Jaye, Georgette Kanmogne, Alfred Njamnshi, T. Dianne Langford, Tufa Gemechu Weyessa, Charles Wood, Mwanza Banda, Mina Hosseinipour, Ned Sacktor, Noeline Nakasuja, Paul Bangirana, Robert Paul, John Joska, Joseph Wong, Michael Boivin, Penny Holding, Betsy Kammerer, Annelies Van Rie, Prudence Ive, Avindra Nath, Kathy Lawler, Clement Adebamowo, Walter Royal Iii, Jeymohan Joseph Jan 2010

Neuroaids In Africa, Kevin Robertson, Jeff Liner, James Hakim, Jean-Louis Sankalé, Igor Grant, Scott Letendre, David Clifford, Amadou Gallo Diop, Assan Jaye, Georgette Kanmogne, Alfred Njamnshi, T. Dianne Langford, Tufa Gemechu Weyessa, Charles Wood, Mwanza Banda, Mina Hosseinipour, Ned Sacktor, Noeline Nakasuja, Paul Bangirana, Robert Paul, John Joska, Joseph Wong, Michael Boivin, Penny Holding, Betsy Kammerer, Annelies Van Rie, Prudence Ive, Avindra Nath, Kathy Lawler, Clement Adebamowo, Walter Royal Iii, Jeymohan Joseph

Nebraska Center for Virology: Faculty Publications

In July 2009, the Center for Mental Health Research on AIDS at the National Institute of Mental Health organized and supported the meeting “NeuroAIDS in Africa.” This meeting was held in Cape Town, South Africa, and was affiliated with the 5th IAS Conference on HIV Pathogenesis, Treatment and Prevention. Presentations began with an overview of the epidemiology of HIV in sub-Saharan Africa, the molecular epidemiology of HIV, HIV-associated neurocognitive disorders (HANDs), and HAND treatment. These introductory talks were followed by presentations on HAND research and clinical care in Botswana, Cameroon, Ethiopia, The Gambia, Kenya, Malawi, Nigeria, Senegal, South Africa, Uganda, …


Functional Properties Of The Hiv-1 Subtype C Envelope Glycoprotein Associated With Mother-To-Child Transmission, Hong Zhang, Marzena Rola, John T. West, Damien C. Tully, Piotr Kubis, Jun He, Chipepo Kankasa, Charles Wood Jan 2010

Functional Properties Of The Hiv-1 Subtype C Envelope Glycoprotein Associated With Mother-To-Child Transmission, Hong Zhang, Marzena Rola, John T. West, Damien C. Tully, Piotr Kubis, Jun He, Chipepo Kankasa, Charles Wood

Nebraska Center for Virology: Faculty Publications

Understanding the properties of viruses capable of establishing infection during perinatal transmission of HIV-1 is critical for designing effective means of limiting transmission. We previously demonstrated that the newly transmitted viruses (in infant) were more fit in growth, as imparted by their envelope glycoproteins, than those in their corresponding mothers. Here, we further characterized the viral envelope glycoproteins from six mother-infant transmission pairs and determined whether any specific envelope functions correlate with HIV-1 subtype C perinatal transmission. We found that most newly transmitted viruses were less susceptible to neutralization by their maternal plasma compared to contemporaneous maternal viruses. However, the …


Chronology And Evolution Of The Hiv-1 Subtype C Epidemic In Ethiopia, Damien C. Tully, Charles Wood Jan 2010

Chronology And Evolution Of The Hiv-1 Subtype C Epidemic In Ethiopia, Damien C. Tully, Charles Wood

Nebraska Center for Virology: Faculty Publications

Objective—To reconstruct the onset date and evolutionary history of the HIV-1 subtype C epidemic in Ethiopia - one of the earliest recorded subtype C epidemics in the world.

Design—HIV-1 C env sequences with a known sampling year isolated from HIV-1 positive patients from Ethiopia between 1984 and 2003.

Methods—Evolutionary parameters including origin and demographic growth patterns were estimated using a Bayesian coalescent-based approach under either strict or relaxed molecular clock models.

Results—Bayesian evolutionary analysis indicated a most recent common ancestor date of 1965 with three distinct epidemic growth phases. Regression analysis of root-to-tip distances revealed a highly similar estimate for …


Enhancement Of Autophagy During Lytic Replication By The Kaposi’S Sarcoma-Associated Herpesvirus Replication And Transcription Activator, Hui-Ju Wen, Zhilong Yang, You Zhou, Charles Wood Jan 2010

Enhancement Of Autophagy During Lytic Replication By The Kaposi’S Sarcoma-Associated Herpesvirus Replication And Transcription Activator, Hui-Ju Wen, Zhilong Yang, You Zhou, Charles Wood

Nebraska Center for Virology: Faculty Publications

Autophagy is one of two major degradation systems in eukaryotic cells. The degradation mechanism of autophagy is required to maintain the balance between the biosynthetic and catabolic processes and also contributes to defense against invading pathogens. Recent studies suggest that a number of viruses can evade or subvert the host cell autophagic pathway to enhance their own replication. Here, we investigated the effect of autophagy on the KSHV (Kaposi’s sarcoma-associated herpesvirus) life cycle. We found that the inhibition of autophagy reduces KSHV lytic reactivation from latency, and an enhancement of autophagy can be detected during KSHV lytic replication. In addition, …


Phocine Distemper Virus Induced Demyelination In The Spinal Cord Of Infected Harbor Seals (Phoca Vitulina), Thomas Siemens Jan 2010

Phocine Distemper Virus Induced Demyelination In The Spinal Cord Of Infected Harbor Seals (Phoca Vitulina), Thomas Siemens

All Theses And Dissertations

Phocine Distemper Virus (PDV) is a Morbillivirus that has been responsible for the death of approximately 40,000 phocid seals in the last three decades. The most commonly reported pathology is virally induced demyelination of the cerebrum and brainstem which leaves axons bare and limits their conductivity of action potentials. While these conditions have been studied at length, there is little mention of spinal cord involvement. This study aims to determine whether demyelination found in the brainstem continues into the cervical spinal cord. The results indicate that demyelination in the cervical spinal cord does not occur alongside the brainstem. It is …


Transcription Analysis Of The Chlorovirus Paramecium Bursaria Chlorella Virus-1, Giane M. Yanai Dec 2009

Transcription Analysis Of The Chlorovirus Paramecium Bursaria Chlorella Virus-1, Giane M. Yanai

School of Biological Sciences: Dissertations, Theses, and Student Research

Paramecium bursaria chlorella virus (PBCV-1), a member of the family Phycodnaviridae, is a large dsDNA, plaque-forming virus that infects the unicellular green alga Chlorella NC64A. The 331 kb PBCV-1 genome is predicted to encode 365 proteins and 11 tRNAs. To follow global transcription during PBCV-1 replication, a microarray containing 50-mer probes to the PBCV-1 365 protein-encoding genes (CDS) was constructed. Competitive hybridization experiments were conducted employing cDNAs from poly A-containing RNAs obtained from cells at seven time points after virus infection. The results led to the following conclusions: i) the PBCV-1 replication cycle is temporally programmed and regulated; ii) 360 …


Human Uterine Natural Killer Cells But Not Blood Natural Killer Cells Inhibit Human Immunodeficiency Virus Type 1 Infection By Secretion Of Cxcl12, Teddy F. Mselle, Aexandra L. Howell, Mimi Ghosh, Charles R. Wira, Charles L. Sentman Nov 2009

Human Uterine Natural Killer Cells But Not Blood Natural Killer Cells Inhibit Human Immunodeficiency Virus Type 1 Infection By Secretion Of Cxcl12, Teddy F. Mselle, Aexandra L. Howell, Mimi Ghosh, Charles R. Wira, Charles L. Sentman

Dartmouth Scholarship

Natural killer (NK) cells derived from the human female reproductive tract (FRT) are phenotypically and functionally distinct from those obtained from peripheral blood. Because the FRT is a primary site of human immunodeficiency virus type 1 (HIV-1) infection in women, we determined whether soluble factors secreted by uterine-derived NK (uNK) cells inhibit HIV-1 infection. Clonal populations of uNK cells were activated with interleukin-12 (IL-12) and IL-15, and conditioned media (CM) from these cultures evaluated for their ability to inhibit infection of cells by HIV-1IIIB, HIV-1NL4.3, and HIV-1HC4 (X4-tropic) or HIV-1BaL (R5-tropic) viruses. We found …


Protection Against Mucosal Shiv Challenge By Peptide And Helper-Dependent Adenovirus Vaccines, Eric A. Weaver, Pramod N. Nehete, Bharti P. Nehete, Stephanie J. Buchl, Donna Palmer, David C. Montefiori, Philip Ng, K. Jagannadha Sastry, Michael A. Barry Oct 2009

Protection Against Mucosal Shiv Challenge By Peptide And Helper-Dependent Adenovirus Vaccines, Eric A. Weaver, Pramod N. Nehete, Bharti P. Nehete, Stephanie J. Buchl, Donna Palmer, David C. Montefiori, Philip Ng, K. Jagannadha Sastry, Michael A. Barry

Nebraska Center for Virology: Faculty Publications

Groups of rhesus macaques that had previously been immunized with HIV-1 envelope (env) peptides and first generation adenovirus serotype 5 (FG-Ad5) vaccines expressing the same peptides were immunized intramuscularly three times with helperdependent adenovirus (HD-Ad) vaccines expressing only the HIV-1 envelope from JRFL. No gag, pol, or other SHIV genes were used for vaccination. One group of the FG-Ad5- immune animals was immunized three times with HD-Ad5 expressing env. One group was immunized by serotype-switching with HD-Ad6, HD-Ad1, and HD-Ad2 expressing env. Previous work demonstrated that serum antibody levels against env were significantly higher in the serotype-switched group than in …


The Role Of Human Endogenous Retroviruses In Renal Cell Carcinoma, Michele D. Tisdale Oct 2009

The Role Of Human Endogenous Retroviruses In Renal Cell Carcinoma, Michele D. Tisdale

Biological Sciences Theses & Dissertations

Human endogenous retroviruses make up approximately 8-9% of the human genome. A number of expressed HERVs, those that are actively transcribing, have been associated with various cancers. Suppression mechanisms that control HERV expression often fail or become more permissive in tissues where expression should be restricted. Previous studies have identified HERV expression in breast cancer tissues, whereas normal tissue HERV expression remained suppressed. In addition, studies of DNA hypermethylation have correlated with the ability to contribute to cancer development. Hypermethylation of several tumor suppressor genes occurs frequently in cancers and alterations in promoter regions could contribute to the development of …


Transitions To And From The Cd4-Bound Conformation Are Modulated By A Single-Residue Change In The Human Immunodeficiency Virus Type 1 Gp120 Inner Domain, Aemro Kassa, Navid Madani, Arne Schön, Hillel Haim, Andrés Finzi, Shi-Hua Xiang, Liping Wang, Amy Princiotto, Marie Pancera, Joel Courter, Amos B. Smith Iii, Ernesto Freire, Peter D. Kwong, Joseph Sodroski Sep 2009

Transitions To And From The Cd4-Bound Conformation Are Modulated By A Single-Residue Change In The Human Immunodeficiency Virus Type 1 Gp120 Inner Domain, Aemro Kassa, Navid Madani, Arne Schön, Hillel Haim, Andrés Finzi, Shi-Hua Xiang, Liping Wang, Amy Princiotto, Marie Pancera, Joel Courter, Amos B. Smith Iii, Ernesto Freire, Peter D. Kwong, Joseph Sodroski

Nebraska Center for Virology: Faculty Publications

Binding to the primary receptor CD4 induces conformational changes in the human immunodeficiency virus type 1 (HIV-1) gp120 envelope glycoprotein that allow binding to the coreceptor (CCR5 or CXCR4) and ultimately trigger viral membrane-cell membrane fusion mediated by the gp41 transmembrane envelope glycoprotein. Here we report the derivation of an HIV-1 gp120 variant, H66N, that confers envelope glycoprotein resistance to temperature extremes. The H66N change decreases the spontaneous sampling of the CD4-bound conformation by the HIV-1 envelope glycoproteins, thus diminishing CD4-independent infection. The H66N change also stabilizes the HIV-1 envelope glycoprotein complex once the CD4-bound state is achieved, decreasing the …


Transcriptome Analysis Of Frog Virus 3, The Type Species Of The Genus Ranavirus, Family Iridoviridae, Sai Majji, V. Thodima, R. Sample, D. Whitley, Y. Deng, J. Mao, V. Gregory Chinchar Sep 2009

Transcriptome Analysis Of Frog Virus 3, The Type Species Of The Genus Ranavirus, Family Iridoviridae, Sai Majji, V. Thodima, R. Sample, D. Whitley, Y. Deng, J. Mao, V. Gregory Chinchar

Faculty Publications

Frog virus 3 is the best characterized species within the genus Ranavirus, family Iridoviridae. FV3's large (similar to 105 kbp) dsDNA genome encodes 98 putative open reading frames (ORFs) that are expressed in a coordinated fashion leading to the sequential appearance of immediate early (IE), delayed early (DE) and late (L) viral transcripts. As a step toward elucidating molecular events in FV3 replication, we sought to identify the temporal Class Of Viral messages. To accomplish this objective an oligonucleotide microarray containing 70-mer probes corresponding to each of the 98 FV3 ORFs was designed and used to examine viral gene expression. …


Controlled Assembly Of Rodlike Viruses With Polymers, Tao Li, Laying Wu, Nisaraporn Suthiwangcharoen, Michael A. Bruckman, Dayton Cash, Joan S. Hudson, Soumitra Ghoshroy, Qian Wang Apr 2009

Controlled Assembly Of Rodlike Viruses With Polymers, Tao Li, Laying Wu, Nisaraporn Suthiwangcharoen, Michael A. Bruckman, Dayton Cash, Joan S. Hudson, Soumitra Ghoshroy, Qian Wang

Faculty Publications

A practical method to assemble rodlike tobacco mosaic virus and bacteriophage M13 with polymers was developed, which afforded a 3D core–shell composite with morphological control.


Comparison Of Immune Correlates, Age Related Changes And Proteomic Profiling Of Healthy Individuals Receiving Influenza Vaccines, Gaurav Basu Apr 2009

Comparison Of Immune Correlates, Age Related Changes And Proteomic Profiling Of Healthy Individuals Receiving Influenza Vaccines, Gaurav Basu

Theses and Dissertations in Biomedical Sciences

The burden of influenza related infections is substantial, both in terms of illness, lives lost and economic impact on society. The degree of impact of influenza related infections is much higher in the elderly population where it is a leading cause of catastrophic disability; greatly affecting the quality of life of elderly persons above 65 years of age. Vaccination is the mainstay for control and prevention of influenza infections. There are two vaccine formulations that are licensed for use at present. The inactivated influenza vaccines (TIIV) which have been used for 60 years in all age groups and the new …


Study Of The Dna Damage Complexes Within The Htlv-1 Tax Oncoprotein Interactome, Sidi Mehdi Belgnaoui Apr 2009

Study Of The Dna Damage Complexes Within The Htlv-1 Tax Oncoprotein Interactome, Sidi Mehdi Belgnaoui

Theses and Dissertations in Biomedical Sciences

Human T-cell leukemia virus type 1 (HTLV-1) is a transforming retrovirus that can give rise to adult T-cell leukemia (ATL) and HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). Tax is a virally encoded oncoprotein that is involved in HTLV-1 mediated cellular transformation. It has been hypothesized that Tax induces genomic instability via repression of the cellular DNA damage repair response. Our laboratory has previously shown that the interaction between Tax and various proteins involved in the DNA-damage response pathway impairs the ability of these proteins to mount an efficient repair response. As part of these observations, we proposed that Tax induces …


Role Of The Human Cytomegalovirus Ie2 Protein On Transcriptional Regulation Of Viral Promoters, Siabhon Michelle Harris Apr 2009

Role Of The Human Cytomegalovirus Ie2 Protein On Transcriptional Regulation Of Viral Promoters, Siabhon Michelle Harris

Theses and Dissertations in Biomedical Sciences

Human cytomegalovirus (HCMV) is a ubiquitous pathogen able to cause severe mortality and morbidity in immuno-compromised individuals. Successful infection by HCMV is dependent on expression of viral genes essential for replication. Immediate early (IE) gene products are the first subset of viral genes to be expressed during infection and function as key transcriptional regulators. IE2 is one the most predominantly expressed IE proteins and is essential for HCMV infection. IE2 transactivates several viral promoters, including those of the essential viral DNA polymerase (UL54) and UL112-113 gene regions. IE2 is also able to autoregulate is own expression and repress expression of …


Interdependent Regulation Of Cytomegalovirus Proteins In Complex, Lisa L. Bolin Apr 2009

Interdependent Regulation Of Cytomegalovirus Proteins In Complex, Lisa L. Bolin

Theses and Dissertations in Biomedical Sciences

Human cytomegalovirus (HCMV) is a ubiquitous herpesvirus that causes significant morbidity and mortality in the immune compromised. Using the mutine cytomegalovirus (MCMV) model, we identified two genes, M140 and M141, which are determinants of macrophage tropism. Monocytes/macrophages are a critical cell type for cytomegalovirus (CMV) pathogenesis as sites of viral latency and by supporting viral replication and disseminating virus throughout the body. We previously found that the localization of the M140/M141 gene products (pM140/pM141) is different when the proteins are co-expressed as compared to their individual expression. When the proteins are individually expressed pM141 localizes diffusely throughout the cytoplasm and, …


Comparison Of Replication-Competent, First Generation, And Helper-Dependent Adenoviral Vaccines, Eric A. Weaver, Pramod N. Nehete, Stephanie S. Buchl, Julien S. Senac, Donna Palmer, Philip Ng, K. Jagannadha Sastry, Michael A. Barry Mar 2009

Comparison Of Replication-Competent, First Generation, And Helper-Dependent Adenoviral Vaccines, Eric A. Weaver, Pramod N. Nehete, Stephanie S. Buchl, Julien S. Senac, Donna Palmer, Philip Ng, K. Jagannadha Sastry, Michael A. Barry

Nebraska Center for Virology: Faculty Publications

All studies using human serotype 5 Adenovirus (Ad) vectors must address two major obstacles: safety and the presence of pre-existing neutralizing antibodies. Helper-Dependent (HD) Ads have been proposed as alternative vectors for gene therapy and vaccine development because they have an improved safety profile. To evaluate the potential of HD-Ad vaccines, we compared replication-competent (RC), first-generation (FG) and HD vectors for their ability to induce immune responses in mice. We show that RC-Ad5 and HD-Ad5 vectors generate stronger immune responses than FG-Ad5 vectors. HD-Ad5 vectors gave lower side effects than RC or FG-Ad, producing lower levels of tissue damage and …


Biomarkers Of Hiv-1 Associated Dementia: Proteomic Investigation Of Sera, Jayme Wiederin, Wojciech Rozek, Fenghai Duan, Pawel Ciborowski Mar 2009

Biomarkers Of Hiv-1 Associated Dementia: Proteomic Investigation Of Sera, Jayme Wiederin, Wojciech Rozek, Fenghai Duan, Pawel Ciborowski

Nebraska Center for Virology: Faculty Publications

Background: New, more sensitive and specific biomarkers are needed to support other means of clinical diagnosis of neurodegenerative disorders. Proteomics technology is widely used in discovering new biomarkers. There are several difficulties with in-depth analysis of human plasma/ serum, including that there is no one proteomic platform that can offer complete identification of differences in proteomic profiles. Another set of problems is associated with heterogeneity of human samples in addition intrinsic variability associated with every step of proteomic investigation. Validation is the very last step of proteomic investigation and it is very often difficult to validate potential biomarker with desired …


Molecular Coevolution Of Pacific Northwest Hantaviruses And Their Host, The Deer Mouse, Peromyscus Maniculatus, Philip Darren Jones Feb 2009

Molecular Coevolution Of Pacific Northwest Hantaviruses And Their Host, The Deer Mouse, Peromyscus Maniculatus, Philip Darren Jones

Dissertations and Theses

Sin Nombre virus (SNV, family Bunyaviridae, genus Hantavirus), hosted by the deer mouse, Peromyscus maniculatus (family Cricetidae, Subfamily Neotominae), is the primary etiological agent of Hantavirus pulmonary syndrome (HPS) in the western United States. HPS, with known pathogenicity only to humans and for which there is no cure or prophylaxis, affects the epithelium of the lungs by making the capillaries leaky, thereby resulting in bilateral infiltrates, and eventually leading to respiratory failure and death by drowning in approximately 38% of hospitalized patients.

In the Americas, Peromyscus has been co-evolving with hantaviruses for approximately 12–20 million years, since the first …


X4 Human Immunodeficiency Virus Type 1 Gp120 Down-Modulates Expression And Immunogenicity Of Codelivered Antigens, Avi-Hai Hovav, Michael Santosuosso, Maytal Bivas-Benita, Andre Plair, Alex Cheng, Mazal Elnekave, Elda Righi, Tao Chen, Satoshi Kashiwagi, Michael W. Panas, Shi-Hua Xiang, Karina Furmanov, Norman L. Letvin, Mark C. Poznansky Jan 2009

X4 Human Immunodeficiency Virus Type 1 Gp120 Down-Modulates Expression And Immunogenicity Of Codelivered Antigens, Avi-Hai Hovav, Michael Santosuosso, Maytal Bivas-Benita, Andre Plair, Alex Cheng, Mazal Elnekave, Elda Righi, Tao Chen, Satoshi Kashiwagi, Michael W. Panas, Shi-Hua Xiang, Karina Furmanov, Norman L. Letvin, Mark C. Poznansky

Nebraska Center for Virology: Faculty Publications

In order to increase the immune breadth of human immunodeficiency virus (HIV) vaccines, strategies such

as immunization with several HIV antigens or centralized immunogens have been examined. HIV-1 gp120

protein is a major immunogen of HIV and has been routinely considered for inclusion in both present and

future AIDS vaccines. However, recent studies proposed that gp120 interferes with the generation of immune

response to codelivered antigens. Here, we investigate whether coimmunization with plasmid-encoded gp120

alters the immune response to other coadministered plasmid encoded antigens such as luciferase or ovalbumin

in a mouse model. We found that the presence of gp120 …