Virology Commons^™

Functional Characterization Of The Human And Murine Schlafen Family Group Iii, Carlos A. Valenzuela

Open Access Theses & Dissertations

The Schlafen (SLFN) family of proteins are known for being encoded by interferon stimulated genes. The family is divided into three groups (I, II, III), for which the largest in size belong to the subgroup III. In humans, group III has the most members (SLFN5, SLFN11, SLFN13 and SLFN14); there is no member of group I and only one member of group II (SLFN12). All human SLFNs belonging to group III have been reported to impair viral protein expression or infection across a variety of viruses. The antiviral function is mediated in SLFN11 and SLFN13 by their tRNase activity, and …

Biology And Ecology Of Aedes (Stegomyia) Aegypti In The Northern Chihuahuan Desert, Adam Joseph Vera

Open Access Theses & Dissertations

Aedes aegypti is a medically important mosquito species that transmits multiple arboviruses, including dengue, chikungunya, Zika, and yellow fever. This mosquito species has expanded its geographical range into expanded into the Northern Chihuahuan Desert to further increase the risk of infection by these viruses in naïve human populations. Although Ae. aegypti is abundant along the U.S.â??Mexico border, the biology and ecology of this mosquito species in this temperate/arid climate region is not understood. The objective of this study was to understand the environmental factors that influence the invasive species of Ae. aegypti abundance, breeding habitat selection, host feeding behavior, and …

Biology And Epidemiology Of Dengue Viruses In The El Paso And The Surrounding Usa And Mexico Border Communities, Pedro Miguel Palermo Infante

Open Access Theses & Dissertations

Dengue is considered one of the most important human arboviral diseases worldwide. Dengue cases have increased in the last three decades in the Americas, especially along the United States (US)- Mexico (MX) border region, where the main vector of dengue, Aedes aegypti mosquito, is widely distributed. Explosive outbreaks of dengue in northern Mexico have been associated with imported and local transmission of dengue in the US border communities, especially in the Southeast Texas area, also known as Rio Grande Valley. Due to the unknown if dengue virus (DENV) is present in other areas in the US border located west of …

Mathematical Modeling Of Potassium Modulated Viral Infection, Zaira Elizabeth Mather

Open Access Theses & Dissertations

In recent years, there is a growing interest in the investigation of using potassium to treat virus infections. In the region of infection, there is a biological observation of extracel- lular potassium level being typically very low whereas the intracellular potassium levels are much higher. There are numerous biological studies showing that elevated potassium levels in the extracellular membrane tends to block virus infections. A recent effort in this direction is a collaborative research conducted by mathematicians and biologists from the University of Texas at El Paso, New Mexico State University, and the University of New Mexico, where we develop …

Examination Of The Association Between C - Reactive Protein(Crp) And Covid-19 Infection Severity And Length Of Hospitalization, Abdulahi Aremu Ayanwale

Open Access Theses & Dissertations

Chronic stress can lead to many systemic complications and low-grade systemic inflammation including increased levels of inflammatory cytokines, such as C-reactive protein (CRP). CRP is a marker of systemic inflammation and is associated with depression and perceived stress. Elevations can result in ineffective immune responses, thereby increasing the risk of complications and mortality from infections. Recent evidence suggests that uncontrolled inflammatory responses associated with COVID 19 are a major determinant of disease severity.  The COVID 19 is transmitted from one person to another through droplets from coughing, sneezing, talking, touching droplets on surfaces and contamination by hand-to-mouth routes. The mechanism …

Structural Characterization Of Two Large Icosahedral Dna Viruses And Their Capsid Assembly Mechanisms, Yuejiao Xian

Open Access Theses & Dissertations

In the last three decades, many large DNA viruses were discovered and grouped into a loosely defined clade of Nucleocytoplasmic Large DNA Viruses (NCLDVs). NCLDVs infect a wide range of hosts from single cellular protists to large animals. Recently, these viruses were classified as a new phylum of Nucleocytoviricota under the kingdom of Bamfordvirae. The genomes of these Nucleocytoviricota viruses (NCVs) are remarkedly large and complicated, containing many cellular genes from all three domains of life, which raised intensive debates on their evolutionary origins. Despite being classified in the same phylum, their physical structures vary and can be roughly classified …

Characterization Of The Anti-Viral Activity Of Schlafen13, Jordan Winfield

Open Access Theses & Dissertations

Schlafen13 (Slfn13) is an enzyme that belongs to the Schlafen family whose expression and function is not very well characterized. The N-terminal has a pseudo dimer structure that contains its catalytic site. There is no characterization functionally or structurally of the C-terminal of Slfn13 other than the prediction of a region with helicase activity. The objective of my Thesis was to increase our understanding of the Slfn family of proteins. Currently, Slfn13 is reported to play a role in the differentiation of monocytes and to function as an endoribonuclease that cleaves tRNA and rRNA molecules in a site-dependent sequence-independent manner. …

Serosurvey For Evidence Of Dengue And West Nile Virus Human Infections In El Paso, Texas, Veronica Suarez

Open Access Theses & Dissertations

Dengue viruses (DENV), including the 4 serotypes are the cause of dengue fever and dengue hemorrhagic fever. The viruses are transmitted by Aedes aegypti mosquitoes in urban communities in tropical, sub-tropical, and temperate regions and are the cause of the highest rate of infection and death of all known Flaviviruses. DENV are endemic in United States (US) -Mexico (MX) border communities in the Rio Grande Valley and suspected of being endemic in Ciudad Juarez, a sister city to El Paso, TX. To determine if DENV were endemic in the El Paso community, cord-blood samples from mothers were tested for antibody …

Investigating The Role Of Parp-1 In Hiv-1 Replication, Sara Garcia

Open Access Theses & Dissertations

Poly (ADP-ribose) Polymerase 1 (PARP-1) is a cellular protein that that has multiple roles in the cell including DNA repair and transcription. PARP-1 has also proven by our laboratory to impair HIV-1 replication in T cells infected with HIV-1 strains entering via CD4/CXCR4. The goal of my Thesis is to increase our understanding of the mechanism implicated in the anti-HIV-1 activity of PARP-1. Initially, I focused my research in deciphering the impact of PARP-1 on the replication of HIV-1 strains entering the cell through the alternative pathway CD4/CCR5. However, technical difficulties prevented answering this question. Nevertheless, aided by the technical …

Characterizing Regulatory Factors Of The Sumoylation System, David Quintanar

Open Access Theses & Dissertations

The effects that influenzaâ??s seasonal epidemics have on human health and the global economy have been clearly noted; while they are indeed very impressive, the impact of influenza pandemics arguably surpass other known infectious agents. Influenza A virus attaches to, enters, and infect cells by releasing its segmented genome which localize to the nucleus then use the hostâ??s cellular machinery to replicate and create viral progeny. The virus is able to hijack transcriptional components as well as to interact with other known and unknown host proteins which ultimately allows for a balance between cell viability and viral propagation. One known …

Defining And Characterizing The Step In The Hiv-1 Viral Life Cycle Affected By Fullerene Derivatives, Zachary Sean Martinez

Open Access Theses & Dissertations

Fullerene derivatives, both C60 and C70, were synthesized and characterized to test their activity against HIV-1 infection. The derivatives tested have previously been reported to inhibit HIV-1 replication and/or in vitro activity of reverse transcriptase. It was found that viruses produced in the presence of low micromolar concentrations of most of these fullerene derivatives exhibit a reduction in viral infectivity greater than 99%. Quantification of virion-associated viral RNA and p24 indicates that RNA packaging and viral production were unremarkable in these viruses. These compounds did not affect infectivity of mature virions, indicating no effect on the early steps of the …

Determining The Role Of Poly [Adp-Ribose] Polymerase 1 (Parp-1) In Retroviral Infection, Luis Valdes Rodriguez

Open Access Theses & Dissertations

Possible links between PARP-1 and HIV-1 have been previously reported but the role of this protein during viral infection has remained elusive. Based on the high evolutionary conservation of PARP-1, from Drosophila to humans, we have been able to counteract the difficulties related with the functional redundancy manifested in the PARP family by studying the influence of PARP-1 on the expression of an endogenous retrovirus using the chicken B lymphoblastoid cell line DT40, this cell line exhibits low PARP-1 functional redundancy and is viable after PARP-1 knockout. We have determined that the transcription level of the endogenous retrovirus RAV-1 is …

Characterizing The Role Of The Fact Complex In Hiv-1 Infection, Angelica Patricia Lopez

Open Access Theses & Dissertations

The lens epithelium-derived growth factor p75 (LEDGF/p75) is a chromatin-bound protein essential for efficient lentiviral integration. Knockdown of this protein severely affects HIV-1 integration levels and thus itâ??s replication. Genome-wide studies have located LEDGF/p75 inside actively transcribed genes where it mediates lentiviral integration. Although this is clearly established, the molecular mechanisms of LEDGF/p75 in HIV-1 infection remain in part elusive.

Using protein-protein interaction assays, we demonstrated that LEDGF/p75 complexes with a chromatin remodeling complex, Facilitates Chromatin Transcription (FACT), a heterodimer of the structure specific recognition protein 1 (SSRP1) and the human homolog of suppressor of Ty 16 (hSpt16). The FACT …

The Characterization Of A Recombinant Virophage Integrase, Martin Christopher Chacon

Open Access Theses & Dissertations

Virophages are satellite-like dsDNA viruses that parasitize giant viruses of the family Mimiviridae. Mavirus is the second virophage discovered that associates with its host virus Cafeteria roenbergensis Virus (CroV). When co-infecting their common host cell Cafeteria roenbergensis, a marine zooplankton that is widely spread throughout the oceans, mavirus will inhibit CroV's replication. In addition, mavirus was shown to share high similarities to the Maverick/Polinton eukaryotic DNA transposons. A coding sequence in mavirus genome (MV02) reveals high homology to retroviral integrases such as those found in HIVs. The putative integrase MV02 is predicted to integrate mavirus DNA into the host genome. …

Characterization Of The Nodamura Virus Rna Dependent Rna Polymerase And Formation Of Rna Replication Complexes In Mammalian Cells, Vincent Ulysses Gant

Open Access Theses & Dissertations

Positive-strand RNA viruses amplify their genomes in membrane-bound structures associated with intracellular membranes and organelles called replication complexes (RCs). Here, we begin to elucidate mechanisms of Nodamura virus (NoV; family Nodaviridae) RC assembly. The literature reports that NoV-infected muscle tissue exhibits mitochondrial aggregation and rearrangement of mitochondrial structure, leading to disorganization of the muscle fibrils. However, the molecular basis for this pathogenesis and the role of mitochondria in NoV infection remained unclear until now. We tested the hypoThesis that NoV establishes RCs in association with mitochondria in cultured mammalian cells at physiological temperature. We used immunofluorescence confocal microscopy and biochemical …

The Sumoylation Of The Non-Structural Protein 1 Of The Influenza A Virus Plays A Dual Role During Viral Infection, Jason Michael Chacon

Open Access Theses & Dissertations

The potential for a highly pathogenic influenza pandemic remains a concern for global health. The ability of the influenza virus to undergo antigenic shift and genetic drift give circulating strains of influenza the high probability of developing resistance to current antiviral therapies. Emerging strains of higher virulence, to which the infected person has not had any previous exposure to viral antigens, pose a greater threat of serious illness and death. Currently, there is no antiviral therapy that is effective against all strains of influenza, emphasizing the need to develop new strategies that target cellular systems required for viral replication to …

Sumoylation Affects Ns1'S Ability To Neutralize The Interferon Response, Jeanette Cecilia Gonzalez

Open Access Theses & Dissertations

It is of huge concern the possibility that at some point in the future we may face a new pandemic involving a highly pathogenic virus due to our current preventive and treatment options to fight this viral disease. The main reason for such limitations is the ability of the virus to go over constant antigenic shifts and drifts on its viral surface proteins HA and NA. The constant mutations that affect this virus cause the need of developing new vaccines for each influenza season. Periodically, the World Health Organization (WHO) reports that around 10% of the world population gets infected …

Characterization Of Ns1 Sumoylation And Its Effect On Influenza A Viral Infection, Katherine Anne Meraz

Open Access Theses & Dissertations

Influenza virus is a contagious respiratory virus responsible for seasonal epidemics and several catastrophic pandemics in the last century. Its genome is comprised of negative sense, single-stranded RNA and, after entering the cell, it is capable of hijacking the host cellular machinery for reproducing its own genetic material. The activation of cellular defenses against influenza viral infection are triggered upon viral entry and help regulate the course of viral infection. This study focused on the interplay between the influenza A virus and the cellular SUMOylation system during viral infection. The first part of this Dissertation deals with the relevance of …

The Characterization Of The Interplay Between Sumoylation And Influenza A Virus, Andres Santos

Open Access Theses & Dissertations

Influenza A virus is a negative sense single stranded RNA virus responsible for multiple devastating pandemics in the past. This virus is capable of entering multiple eukaryotic hosts, sequestering, and using their cellular machinery for its own replicative purposes. This plethora of molecular events is all orchestrated through a shockingly limited repertoire of only 11 viral proteins. All of which are all strictly dependent on cellular processes such as post-transcriptional regulation, protein translation, post-translational modifications, etc. This study is focused on the characterization of the interplay between Influenza A virus and the cellular SUMOylation system. The first part of this …

Expression And Characterization Of The Major Capsid Protein (Mcp) Of A Giant Marine Virus: Cafeteria Roenbergensis Virus, Sayan Chakraborty

Open Access Theses & Dissertations

The oceans play significant roles in maintaining the climate on Earth and providing nutrients to the whole biosphere. Oceanic microbes produce approximately half of the Earth's oxygen. It has been shown that the populations of microbial communities in oceans are largely regulated by viral infection and thus affect the marine ecosystem. Cafeteria roenbergensis Virus (CroV) is a giant marine virus with a linear, double stranded, and AT-rich DNA genome. The genome of CroV has a size of 744kb and encodes for 544 predicted genes. CroV derived its name from its host, a unicellular marine zooplankton Cafeteria roenbergensis (Cro) that is …

Sumoylation Exerts Minimal Effects On The Splicing Regulatory Activity Of The Influenza A Virus Non-Structural Protein Ns1, Griselda Melendez

Open Access Theses & Dissertations

One of the greatest challenges facing the development of a universal treatment for influenza infection is the virus's ability to mutate rapidly and produce new antigenic properties. Targeting the viral components of one strain does not ensure that the treatment will be effective with a newly developed strain. One alternative would be to develop therapies that target cellular factors the virus depends on for survivability. One of these factors is the cellular SUMOylation system. We have previously demonstrated that the Small Ubiquitin-like MOdifier (SUMO) interacts with the influenza virus by SUMOylating several viral proteins and by affecting the interferon blocking …

Role Of Post-Translational Modifications In The Hiv Cofactor Activity Of Ledgf/P75, Denisse Adriana Gutierrez

Open Access Theses & Dissertations

see document.

Further Characterization Of The Nodamura Virus Rna2 3'-Terminal Stem Loop Structure And Its Role In Viral Rna Replication, Joshua Frederick

Open Access Theses & Dissertations

Nodamura virus (NoV) is an excellent model system for studying many aspects of the life cycle of positive-strand RNA viruses. NoV's simple genome organization and ability to replicate its genome to high levels in a wide variety of host cells, including plants, yeast, insects and mammals (Ball et al., 1992; Garzon et al., 1978, 1990; Murphy et al., 1970; Price et al., 2005; Scherer & Hurlbut, 1967; Selling et al., 1990; reviewed by Ball & Johnson, 1998), make it a prime model system for studying the basic mechanisms of viral RNA replication. Other positive-strand RNA viruses, including those that are …

Molecular Mechanisms Of Poly [Adp-Ribose] Polymerase-1 In Hiv-1 Infection, Daniel Reyes

Open Access Theses & Dissertations

Poly (ADP-ribose) polymerase-1 (PARP-1) is a cellular enzyme involved in genome stability and transcriptional regulation. The role of this protein in HIV-1 infection is largely controversial. Some reports indicated a fundamental role of PARP-1 in HIV-1 DNA integration and results from other laboratories do not support these conclusions. An important characteristic in all these experiments is that the HIV-1 target cells that were used express, in addition to PARP-1, the functional homologue PARP-2. We evaluated the role of PARP-1 in the chicken B lymphoblastoid cell line DT40. These cells naturally lack PARP-2 and support the early steps of HIV infection. …

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

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 …

Cis-Acting Signals For Replication Of Nodamura Virus Rna1, John Joseph Rosskopf

Open Access Theses & Dissertations

The family Nodaviridae is comprised of two genera: the alphanodaviruses that infect insects and the betanodaviruses, which have been isolated only from fish. Nodamura virus (NoV), the type species of the alphanodavirus genus, can lethally infect both insects (mosquitoes, honey bees, and wax moth larvae) and mammals (suckling mice and suckling hamsters). In addition, nodavirus RNAs can replicate in a wide variety of host cells, including those of mammalian, insect, plant, and yeast origin, when introduced by transfection. The nodavirus positive strand RNA genome is naturally segregated into two segments. RNA1 encodes the viral RNA-dependent RNA polymerase (RdRp) that replicates …

The Role Of Rna Secondary Structure In Replication Of Nodamura Virus Rna2, John Howard Upton

Open Access Theses & Dissertations

Our laboratory studies genome replication of positive-strand RNA viruses, using a reverse-genetic system in yeast cells. Nodamura virus (NoV) provides an excellent model system for the study of RNA replication due to its genetic simplicity, its robust yield of replication products, and its ability to replicate in a wide variety of host cells. NoV contains a bipartite positive strand RNA genome: RNA1 encodes the viral RNA replicase, while RNA2 encodes the capsid protein. The role of RNA secondary structure in the genome replication of other RNA viruses has been well established. For NoV, sequences at the 3' end of RNA2 …