Virology Commons^™

Antibiotic Resistance Crisis Spurring Phage Therapy Research, Cameron Miguel Perry

Chancellor’s Honors Program Projects

No abstract provided.

Proteomic Analysis Of Mycobacteriophage Crimd, William Moeller

Undergraduate Honors Theses

Bacteriophages represent a large portion of the biomatter on our planet, and many of them have yet to be fully characterized. Here we discuss the proteomic analysis of a particular Bacteriophage, Mycobacteriophage CrimD. This phage was discovered on the Campus of William & Mary and has had its genome characterized. We took the next logical step of proteomic analysis.

In our analyses we made use high pressure liquid chromatography paired with linear ion trap mass spectrometry to analyze the proteome of CrimD at specific time points after the infection of its host, Mycobacterium smegmatis. Additionally, we used nanospray ionization with in-house ...

Hiv-1 Drug Resistance To Integrase Strand Transfer Inhibitors In Hiv-1 Non-B Subtypes, Emmanuel Ndashimye

Electronic Thesis and Dissertation Repository

Human immunodeficiency syndrome (HIV-1) has infected over 75 million people and over 35 million have succumbed to virus related illnesses. Despite access to a variety of antiretroviral therapy (ART) options, ART programs have been disproportionally spread in the world with low-and middle-income countries (LMICs) facing challenges to access the most potent ART options. With less potent ART remaining in use in LMICs, HIV-1 drug resistance (HIVDR) presents a growing challenge in LMICs. Since approval of the first-generation integrase strand transfer inhibitor (INSTIs), Raltegravir (RAL) in 2007, INSTIs remain the best choice as a backbone of ART. Access to second generation ...

B25: Generation And Characterization Of Sars-Cov-2 Spike Protein-Pseudotyped Lentivirus Particles For Use In Neutralizing Antibody Titer Testing Of Human Serum, Luis Sanchez

Annual Research Symposium

No abstract provided.

B16: Chikungunya Virus Time Course Infection Of Human Macrophages, Madison Gray, Israel Guerrero-Arguero, Antonio Solis Leal, Richard Robison, Brad Burges, Brett Pickett

Annual Research Symposium

Chikungunya virus (CHIKV) is an Alphavirus spread by Aedes spp. mosquitoes and is responsible for infecting 1.1 million people per year worldwide, including a large epidemic in the western hemisphere in 2014-2015. During the body’s immune response to CHIKV, human macrophages become infected after phagocytosis of CHIKV and undergo induced apoptosis, catalyzing the virus spread in the body. It is presently unclear what macrophage genes, functions, and intracellular signaling pathways are impacted during the early, intermediate, and late stages of CHIKV infection. Therefore we quantified the transcriptional response of human macrophage cells infected with CHIKV at two different ...

Characterization Of Novel Chlorovirus Glycosyltransferases That Synthesize Atypical Glycans, Eric Noel

Dissertations and Theses in Biological Sciences

Giant dsDNA chloroviruses encode a diverse repertoire of glycosyltransferases (GTases) and methyltransferases (MTases) that biosynthesize unusual, methylated sugars independent of their host chlorella-like green algae prompting a reexamination of glycobiology systems. Unlike most other viruses, the prototype chlorovirus PBCV-1 encodes most, if not all, of the machinery required to glycosylate its major capsid protein (MCP). The structures of the four N-linked glycans do not resemble any other glycans in the three domains of life. Here, we investigated the potential involvement of chlorovirus- encoded putative GTases and MTases in glycosylation of the viral MCP. First, we aimed to generate site-directed ...

Effectiveness Of Pathogen-Specific Passive Antibodies To Mitigate Infectious Diseases In Apis Mellifera, Tanner Nordseth

Honors Thesis

Honeybees (Apis mellifera) are widely recognized as a vital part of the global ecosystem and the world's food supply due to their pivotal role in the pollination of both natural and agricultural flora. Colony Collapse Disorder (CCD) is an emerging phenomenon characterized by a colony's worker bees deserting the hive and leaving the queen behind. This usually results in colony failure. CCD is a multifactorial issue, with many environmental stressors and pathogens playing a role. Deformed Wing Virus (DWV) has been identified as a leading cause in this phenomenon. Paenibacillus larvae (P. larvae) is another lethal pathogen that ...

Development Of Potency, Breadth And Resilience To Viral Escape Mutations In Sars-Cov-2 Neutralizing Antibodies [Preprint], Frauke Muecksch, Shurong Hou, Celia A. Schiffer, Michel Nussenzweig, Pamela J. Bjorkman, Theodora Hatziioannou, Paul Bieniasz

University of Massachusetts Medical School Faculty Publications

Antibodies elicited in response to infection undergo somatic mutation in germinal centers that can result in higher affinity for the cognate antigen. To determine the effects of somatic mutation on the properties of SARS-CoV-2 spike receptor-binding domain (RBD)-specific antibodies, we analyzed six independent antibody lineages. As well as increased neutralization potency, antibody evolution changed pathways for acquisition of resistance and, in some cases, restricted the range of neutralization escape options. For some antibodies, maturation apparently imposed a requirement for multiple spike mutations to enable escape. For certain antibody lineages, maturation enabled neutralization of circulating SARS-CoV-2 variants of concern and ...

Inhibition Of Zika Virus Replication By G-Quadruplex-Binding Ligands, Indian Institute Of Technology Indore, Aryamav Pattnaik, Bikash R. Sahoo, Uma Shankar, Asit K. Pattnaik, Amit Kumar, Debasis Nayak

Virology Papers

Zika virus (ZIKV), a mosquito-transmitted Flavivirus, emerged in the last decade causing serious diseases and affecting human health globally. Currently, no licensed vaccines or antivirals are available to combat ZIKV, although several vaccine candidates are in the pipeline. In recent years, the presence of non-canonical G-quadruplex (GQ) secondary structures in viral genomes has ignited significant attention as potential targets for antiviral strategy. In this study, we identified several novel conserved potential GQ structures by analyzing published ZIKV genome sequences using an in-house algorithm. Biophysical and biochemical analysis of the RNA sequences containing these potential GQ sequences suggested the existence of ...

A Novel Dna And Protein Combination Covid-19 Vaccine Formulation Provides Full Protection Against Sars-Cov-2 In Rhesus Macaques, Yuzhong Li, Guangnan Hu, Shixia Wang, Qihan Li, Shan Lu, Wei Cun

COVID-19 Publications by UMMS Authors

The current study aims to develop a safe and highly immunogenic COVID-19 vaccine. The novel combination of a DNA vaccine encoding the full-length Spike (S) protein of SARS-CoV-2 and a recombinant S1 protein vaccine induced high level neutralizing antibody and T cell immune responses in both small and large animal models. More significantly, the co-delivery of DNA and protein components at the same time elicited full protection against intratracheal challenge of SARS-CoV-2 viruses in immunized rhesus macaques. As both DNA and protein vaccines have been proven safe in previous human studies, and DNA vaccines are capable of eliciting germinal center ...

Unique Structural Solution From A Vh3-30 Antibody Targeting The Hemagglutinin Stem Of Influenza A Viruses, Wayne D. Harshbarger, Derrick Deming, Gordon J. Lockbaum, Nattapol Attatippaholkun, Maliwan Kamkaew, Shurong Hou, Mohan Somasundaran, Jennifer P. Wang, Robert W. Finberg, Quan Karen Zhu, Celia A. Schiffer, Wayne A Marasco

Schiffer Lab Publications

Broadly neutralizing antibodies (bnAbs) targeting conserved influenza A virus (IAV) hemagglutinin (HA) epitopes can provide valuable information for accelerating universal vaccine designs. Here, we report structural details for heterosubtypic recognition of HA from circulating and emerging IAVs by the human antibody 3I14. Somatic hypermutations play a critical role in shaping the HCDR3, which alone and uniquely among V_H3-30 derived antibodies, forms contacts with five sub-pockets within the HA-stem hydrophobic groove. 3I14 light-chain interactions are also key for binding HA and contribute a large buried surface area spanning two HA protomers. Comparison of 3I14 to bnAbs from several defined ...

Crystal Structure Of Sars-Cov-2 Main Protease In Complex With The Non-Covalent Inhibitor Ml188, Gordon J. Lockbaum, Archie C. Reyes, Jeong Min Lee, Ronak Tilvawala, Ellen A. Nalivaika, Akbar Ali, Nese Kurt Yilmaz, Paul R. Thompson, Celia A. Schiffer

COVID-19 Publications by UMMS Authors

Viral proteases are critical enzymes for the maturation of many human pathogenic viruses and thus are key targets for direct acting antivirals (DAAs). The current viral pandemic caused by SARS-CoV-2 is in dire need of DAAs. The Main protease (M(pro)) is the focus of extensive structure-based drug design efforts which are mostly covalent inhibitors targeting the catalytic cysteine. ML188 is a non-covalent inhibitor designed to target SARS-CoV-1 M(pro), and provides an initial scaffold for the creation of effective pan-coronavirus inhibitors. In the current study, we found that ML188 inhibits SARS-CoV-2 M(pro) at 2.5 microM, which is ...

Innate Lymphoid Cells And Disease Tolerance In Sars-Cov-2 Infection [Preprint], Noah J. Silverstein, Yetao Wang, Zachary Manickas-Hill, Claudia C. Carbone, Ann Dauphin, Mgh Covid-19 Collection & Processing Team, Jonathan Z. Li, Bruce D. Walker, Xu G. Yu, Jeremy Luban

University of Massachusetts Medical School Faculty Publications

BACKGROUND: Risk of severe coronavirus disease 2019 (COVID-19) increases with age, is greater in males, and is associated with decreased numbers of blood lymphoid cells. Though the reasons for these robust associations are unclear, effects of age and sex on innate and adaptive lymphoid subsets, including on homeostatic innate lymphoid cells (ILCs) implicated in disease tolerance, may underlie the effects of age and sex on COVID-19 morbidity and mortality.

METHODS: Flow cytometry was used to quantitate subsets of blood lymphoid cells from people infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), comparing those hospitalized with severe COVID-19 (n=40 ...

Disruption Of Cellular P-Bodies During An Adenovirus Infection​, La`Quita Randolph, Kevin Neubrecht, Kasey A. Karen

Graduate Research Posters

Adenovirus has made major contributions in medicine by serving as a model DNA virus to study other viruses, such as human papillomavirus (HPV). Adenoviruses are a diverse family of nonenveloped, double-stranded DNA viruses that are ubiquitous to animals and humans. There are over 67 serotypes of human adenoviruses that can cause a variety of illnesses including, gastroenteritis, conjunctivitis and respiratory infections. Adenovirus can cause these infections by invading host cells and producing an environment that is favorable for viral replication. During the early phases of infection, adenovirus expresses various viral proteins such as E4 11k, which has multiple functions. One ...

The 20th Anniversary Meeting Of The Rocky Mountain Virology Association, Joel Rovnak, Laura A. St Clair, Carley Mcalister, Chinemerem P. Ogbu, Jessica Smolenske, Randall J. Cohrs, Rushika Perera

Virology Papers

Due to the COVID-19 pandemic and multiple devastating forest fires, the 2020 meeting of the Rocky Mountain Virology Association was held virtually. The three-day gathering featured talks describing recent advances in virology and prion research. The keynote presentation described the measles virus paradox of immune suppression and life-long immunity. Special invited speakers presented information concerning visualizing antiviral effector cell biology in mucosal tissues, uncovering the T-cell tropism of Epstein-Barr virus type 2, a history and current survey of coronavirus spike proteins, a summary of Zika virus vaccination and immunity, the innate immune response to flavivirus infections, a discussion concerning prion ...

High Prevalence Of Pre-Existing Serological Cross-Reactivity Against Severe Acute Respiratory Syndrome Coronavirus-2 (Sars-Cov-2) In Sub-Saharan Africa, For Yue Tso, Salum J. Lidenge, Phoebe B. Peña, Ashley A. Clegg, John R. Ngowi, Julius Mwaiselage, Owen Ngalamika, Peter Julius, John T. West, Charles Wood

Virology Papers

Objective: Significant morbidity and mortality have occurred in the USA, Europe, and Asia due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), whereas the numbers of infections and deaths in sub-Saharan Africa (SSA) have remained comparatively low. It has been hypothesized that exposure of the population in SSA to other coronaviruses prior to the COVID-19 pandemic resulted in some degree of cross-protection against SARS-CoV-2 infection and pathogenesis. We evaluated this hypothesis by comparing SARS-CoV-2 cross-reactive antibodies in pre-pandemic plasma samples collected from SSA and the USA.

Method: Pre-COVID-19 pandemic plasma samples from SSA and the USA were collected and tested by ...

Strategies Targeting Hemagglutinin As A Universal Influenza Vaccine, Brianna L. Bullard, Eric A. Weaver

Virology Papers

Influenza virus has significant viral diversity, both through antigenic drift and shift, which makes development of a vaccine challenging. Current influenza vaccines are updated yearly to in- clude strains predicted to circulate in the upcoming influenza season, however this can lead to a mismatch which reduces vaccine efficacy. Several strategies targeting the most abundant and im- munogenic surface protein of influenza, the hemagglutinin (HA) protein, have been explored. These strategies include stalk-directed, consensus-based, and computationally derived HA immunogens. In this review, we explore vaccine strategies which utilize novel antigen design of the HA protein to improve cross-reactive immunity for development ...

Zika Virus Infection Induces Endoplasmic Reticulum Stress And Apoptosis In Placental Trophoblasts, Philma Glora Muthuraj, Prakask K. Sahoo, Madison Kraus, Taylor Bruett, Arun S. Annamalai, Aryamav Pattnaik, Asit K. Pattnaik, Siddappa N. Byrareddy, Sathish Kumar Natarajan

Virology Papers

Zika virus (ZIKV) infection to a pregnant woman can be vertically transmitted to the fetus via the placenta leading to Congenital Zika syndrome. This is characterized by microcephaly, retinal defects, and intrauterine growth retardation. ZIKV induces placental trophoblast apoptosis leading to severe abnormalities in the growth and development of the fetus. However, the molecular mechanism behind ZIKV-induced apoptosis in placental trophoblasts remains unclear. We hypothesize that ZIKV infection induces endoplasmic reticulum (ER) stress in the trophoblasts, and sustained ER stress results in apoptosis. HTR-8 (HTR-8/SVneo), a human normal immortalized trophoblast cell and human choriocarcinoma-derived cell lines (JEG-3 and JAR ...

Chlorovirus Pbcv-1 Multidomain Protein A111/114r Has Three Glycosyltransferase Functions Involved In The Synthesis Of Atypical N-Glycans, Eric Noel, Anna Notaro, Immacolata Speciale, Garry A. Duncan, Cristina De Castro, James L. Van Etten

Virology Papers

The structures of the four N-linked glycans from the prototype chlorovirus PBCV-1 major capsid protein do not resemble any other glycans in the three domains of life. All known chloroviruses and antigenic variants (or mutants) share a unique conserved central glycan core consisting of five sugars, except for antigenic mutant virus P1L6, which has four of the five sugars. A combination of ge- netic and structural analyses indicates that the protein coded by PBCV-1 gene a111/114r, conserved in all chloroviruses, is a glycosyltransferase with three putative domains of approximately 300 amino acids each. Here, in addition to in silico ...

High Prevalence Of Pre-Existing Serological Cross-Reactivity Against Severe Acute Respiratory Syndrome Coronavirus-2 (Sars- Cov-2) In Sub-Saharan Africa, For Yue Tso, Salum Lidenge, Phoebe B. Peña, Ashley A. Clegg, John R. Ngowi, Julius Mwaiselage, Owen Ngalamika, Peter Julius, John T. West, Charles Wood

Virology Papers

Objective: Significant morbidity and mortality have occurred in the USA, Europe, and Asia due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), whereas the numbers of infections and deaths in sub-Saharan Africa (SSA) have remained comparatively low. It has been hypothesized that exposure of the population in SSA to other coronaviruses prior to the COVID-19 pandemic resulted in some degree of cross-protection against SARS-CoV-2 infection and pathogenesis. We evaluated this hypothesis by comparing SARS-CoV-2 cross-reactive antibodies in pre-pandemic plasma samples collected from SSA and the USA.

Method: Pre-COVID-19 pandemic plasma samples from SSA and the USA were collected and tested by ...