Virology Commons^™

Macrophage-Associated Wound Healing Contributes To African Green Monkey Siv Pathogenesis Control, Fredrik Barrenas, Kevin Raehtz, Cuiling Xu, Lynn Law, Richard R. Green, Guido Silvestri, Steven E. Bosinger, Andrew Nishida, Qingsheng Li, Wuxun Lu, Jianshui Zhang, Matthew J. Thomas, Jean Chang, Elise Smith, Jeffrey M. Weiss, Reem A. Dawoud, George H. Richter, Anita Trichel, Dongzhu Ma, Xinxia Peng, Jan Komorowski, Cristian Apetrei, Ivona Pandrea, Michael Gale Jr.

Nebraska Center for Virology: Faculty Publications

Natural hosts of simian immunodeficiency virus (SIV) avoid AIDS despite lifelong infection. Here, we examined how this outcome is achieved by comparing a natural SIV host, African green monkey (AGM) to an AIDS susceptible species, rhesus macaque (RM). To asses gene expression profiles from acutely SIV infected AGMs and RMs, we developed a systems biology approach termed Conserved Gene Signature Analysis (CGSA), which compared RNA sequencing data from rectal AGM and RM tissues to various other species. We found that AGMs rapidly activate, and then maintain, evolutionarily conserved regenerative wound healing mechanisms in mucosal tissue. The wound healing protein fibronectin …

Identifiying High Risk Areas Of Zika Virus Infection By Meteorological Factors In Columbia, Lung-Chang Chien, Francisco Sy, Adriana Perez

Environmental & Global Health Faculty Research

Background Several Zika virus (ZIKV) outbreaks have occurred since October 2015. Because there is no effective treatment for ZIKV infection, developing an effective surveillance and warning system is currently a high priority to prevent ZIKV infection. Despite Aedes mosquitos having been known to spread ZIKV, the calculation approach is diverse, and only applied to local areas. This study used meteorological measurements to monitor ZIKV infection due to the high correlation between climate change and Aedes mosquitos and the convenience to obtain meteorological data from weather monitoring stations. Methods This study applied the Bayesian structured additive regression modeling approach to include …

Dose Effects Of Recombinant Adenovirus Immunization In Rodents, Eric A. Weaver

Nebraska Center for Virology: Faculty Publications

Recombinant adenovirus type 5 (rAd) has been used as a vaccine platform against many infectious diseases and has been shown to be an effective vaccine vector. The dose of the vaccine varies significantly from study to study, making it very diffcult to compare immune responses and vaccine effcacy. This study determined the immune correlates induced by serial dilutions of rAd vaccines delivered intramuscularly (IM) and intranasally (IN) to mice and rats. When immunized IM, mice had substantially higher antibody responses at the higher vaccine doses, whereas, the IN immunized mice showed a lower response to the higher rAd vaccine doses. …

The Vaccinia Virus (Vacv) B1 And Cellular Vrk2 Kinases Promote Vacv Replication Factory Formation Through Phosphorylation-Dependent Inhibition Of Vacv B12, Amber B. Rico, Zhigang Wang, Annabel T. Olson, Alexandria C. Linville, Brianna L. Bullard, Eric A. Weaver, Clinton Jones, Matthew S. Wiebea

Nebraska Center for Virology: Faculty Publications

Comparative examination of viral and host protein homologs reveals novel mechanisms governing downstream signaling effectors of both cellular and viral origin. The vaccinia virus B1 protein kinase is involved in promoting multiple facets of the virus life cycle and is a homolog of three conserved cellular enzymes called vaccinia virus-related kinases (VRKs). Recent evidence indicates that B1 and VRK2 mediate a common pathway that is largely uncharacterized but appears independent of previous VRK substrates. Interestingly, separate studies described a novel role for B1 in inhibiting vaccinia virus protein B12, which otherwise impedes an early event in the viral lifecycle. Herein, …

A Role Of Ubiquitin Regulatory X-Domain Containing Proteins (Ubxn6) In Antiviral Immunity, Harshada Ketkar, Harshada Ketkar

NYMC Student Theses and Dissertations

The roles of UBXNs in the regulation of antiviral immune responses have not been much explored. Previous work in our lab identified UBXN1 as a negative regulator of the retinoic acid-inducible gene-I (RIG-I) like receptors (RLR) pathway and UBXN3B as a positive regulator of stimulator-of-interferon Genes (STING) -mediated immune responses. In this study, I aimed to determine the member of UBXNs as a positive regulator of ribonucleic acid (RNA) virus infection-induced innate immune responses. By using an interferon stimulated response element (ISRE)-driven luciferase reporter assay that monitors the activity of type I/III interferon (IFN)-induced janus kinase (JAK) - signal transducer …

Rig-I-Like Receptors Direct Inflammatory Macrophage Polarization Against West Nile Virus Infection., Amy E. L. Stone, Richard Green, Courtney Wilkins, Emily A. Hemann, Michael Gale Jr.

College of Osteopathic Medicine (TUN) Publications and Research

RIG-I-Like Receptors (RLRs) RIG-I, MDA5, and LGP2, are vital pathogen recognition receptors in the defense against RNA viruses. West Nile Virus (WNV) infections continue to grow in the US. Here, we use a systems biology approach to define the contributions of each RLR in the innate immune response to WNV. Genome-wide RNAseq and bioinformatics analyses of macrophages from mice lacking either RLR reveal that the RLRs drive distinct immune gene activation and response polarization to mediate an M1/inflammatory signature while suppressing the M2/wound healing phenotype. While LGP2 functions to modulate inflammatory signaling, RIG-I and MDA5 together are essential for M1 …

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

Graduate Theses/Dissertations

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) …

Longitudinal Quantification Of Adenovirus Neutralizing Responses In Zambian Mother-Infant Pairs: Impact Of Hiv-1 Infection And Its Treatment, Sara R. Privatt, Brianna L. Bullard, Eric A. Weaver, Charles Wood, John T. West

Nebraska Center for Virology: Faculty Publications

Vaccination offers the most cost-effective approach to limiting the adverse impact of infectious and neoplastic diseases that reduce the quality of life in sub-Saharan Africa (SSA). However, it is unclear what vaccine vectors would be most readily implementable in the setting and at what age they should be applied for maximal efficacy. Adenoviruses (Ad) and Ad-based vectors have been demonstrated to induce effective humoral and cellular immune responses in animal models and in humans. However, because immunity associated with Ad infection is lifelong, there exists a debate as to whether pre-existing immunity might decrease the efficacy of Ad vectored vaccines. …

Environmental Sampling Techniques For Herd-Level Surveillance Of Bovine Viral Diarrhea Virus, Jaden Carlson

School of Veterinary and Biomedical Sciences: Dissertations, Theses, and Student Research

Control of Bovine Viral Diarrhea Virus (BVDV) relies on resource-intensive individual animal sampling to detect and remove persistently infected (PI) cattle. Herd-level surveillance tools would be useful for herds with unknown BVDV status and for monitoring herds with BVDV-free status. The overall objective of this thesis is to explore the viability of BVDV surveillance at a herd-level using samples collected without handling individual animals. The first objective was to determine the feasibility of using stable flies as a sampling tool to detect BVDV. The second objective was to determine the feasibility of using drinking water to detect BVDV. To accomplish …

Intratypic Genetic Variability Of Human Adenovirus Type 4: Implication For Viral Pathogenesis, Camden Roy Bair

Biomedical Sciences ETDs

Human adenovirus type 4 (HAdV-E4) is a causative agent of acute respiratory disease and conjunctivitis worldwide. Two major lineages of HAdV-E4 genomic variants have been identified by their distinct BamHI restriction profiles: prototype-like (p-like) strains and the a-like genomic variants. Recent molecular epidemiology studies have shown a predominance of a-like genomic variants detected in association with disease which suggests a-like strains have a fitness advantage or they may be more pathogenic. The impact of HAdV-E4 intratypic genetic variability on in vitro and in vivo phenotypes relevant to pathogenesis is a major gap in knowledge. I hypothesize that HAdV-E4 comprises two …

Role Of Gp120 Glycosylation In Sexual Transmission Of Hiv, Yingxue Sun, Adam Meadows, Najwa Zebian, Eric Arts, Carole Creuzenet

Western Research Forum

Background:

In chronic HIV patients, the viral populations are genetically diverse due to mutations introduced by the viral reverse transcriptase during HIV replication. However, more than 80% new infections result from single transmission founder (TF) viruses; therefore, targeting the TFs is key to control AIDS worldwide.

Gp120 is a glycosylated envelope protein required for HIV infection, propagation, and transmission. Glycans on gp120 influence HIV infectivity through their interactions with lectins, the carbohydrate-binding immune proteins in the host mucosa. To transmit sexually, viruses must overcome the lectin traps to access more target T cells.

Hypothesis:

TF viruses are less likely to …

Stalking Flu: Development And Characterization Of A Broadly Neutralizing Monoclonal Antibody Targeting The Influenza Hemagglutinin Stem, Elizabeth Newman

NYMC Student Theses and Dissertations

Seasonal epidemics caused by influenza A viruses (IAV) result in an estimated 290,000- 650,000 deaths worldwide each year (17). While antivirals targeted to influenza exist, resistance to these drugs is increasing and regular vaccination remains the most effective way to prevent infection (26, 73, 99). However due to the persistence of antigenic drift and shift, influenza vaccines must be updated each season and antigenic mismatches can reduce efficacy (24, 118). Immunity to influenza either from vaccination or infection is principally mediated by antibodies generated to one of its major surface proteins, Hemagglutinin (HA). HA is a homotrimer, each monomer HA0 …

A Case-Study Approach To Investigate Transmission, Co-Infection, And Clinical Sequelae During Epidemics Of Dengue And Ebola Virus Disease, Jennifer Elizabeth Giovanni

LSU Doctoral Dissertations

From within their ecologic niches, zoonotic viruses emerge from animal reservoirs into the edges and centers of human habitation to exploit opportunities for unabated transmission within immunologically–naïve populations. Our understanding of where, in whom, and how these viruses emerge is under direct challenge, driving the evolution of modern infectious disease epidemiology within a rapidly-connected global community. The studies presented herein are based on analyses of both aggregate and case-level data, which, we argue, provide unique insight into the complexities of transmission, co-infection, and clinical sequelae occurring within, and arising from, epidemics of emerging zoonotic viruses. In Chapter II, we investigate …

Synthesis And Characterization Of A Long-Acting Emtricitabine Prodrug Nanoformulation, Ibrahim M. Ibrahim

Theses & Dissertations

The introduction of highly active antiretroviral therapy led to a paradigm shift in the management of HIV/AIDS changing a disease considered “a death sentence” to “a manageable chronic disease”. Nevertheless, challenges exist for successful treatment of HIV, including patient adherence to the complex daily regimens and the inability of current formulations to target viral sanctuaries. Introduction of nanoformulated antiretroviral therapy (ART) is a promising alternative to tackle these challenges. Our laboratory has been focusing on developing long-acting (LA) nanoformulated antiretrovirals and has succeeded in developing LA integrase inhibitors. However, challenges for this approach extend to a range of short-acting hydrophilic …

Development Of A Long-Acting Nanoformulation Of Dolutegravir For Prevention And Treatment Of Hiv-1 Infection, Brady Sillman

Theses & Dissertations

Dolutegravir (DTG) is a potent human immunodeficiency virus type 1 (HIV-1) integrase strand-transfer inhibitor (INSTI) with a high barrier to viral drug resistance. However, opportunities to improve its profile abound. These include extending the drug’s apparent half-life, increasing penetrance to “putative” viral reservoirs, and reducing inherent toxicities. These highlight, in part, the need for long-acting, slow effective release antiretroviral therapy (LASER ART) delivery schemes. A long-acting (LA) DTG was made by synthesizing a hydrophobic and lipophilic prodrug encased with poloxamer (P407) surfactant. This modified DTG (MDTG) reduced systemic metabolism and polarity, increased lipophilicity and membrane permeability, improved encapsulation, and formed …

Development And Evaluation Of A One-Step Multiplex Real-Time Taqman® Rt-Qpcr Assay For The Detection And Genotyping Of Equine G3 And G14 Rotaviruses In Fecal Samples, Mariano Carossino, Maria E. Barrandeguy, Erdal Erol, Yanqiu Li, Udeni B. R. Balasuriya

Veterinary Science Faculty Publications

Background: Equine rotavirus A (ERVA) is the leading cause of diarrhea in neonatal foals and has a negative impact on equine breeding enterprises worldwide. Among ERVA strains infecting foals, the genotypes G3P[12] and G14P[12] are the most prevalent, while infections by strains with other genomic arrangements are infrequent. The identification of circulating strains of ERVA is critical for diagnostic and surveillance purposes, as well as to understand their molecular epidemiology. Current genotyping methods available for ERVA and rotaviruses affecting other animal species rely on Sanger sequencing and are significantly time-consuming, costly and labor intensive. Here, we developed the first one-step …

Regulation Of Vaccinia Virus Replication: A Story Of Viral Mimicry And A Novel Antagonistic Relationship Between Vaccinia Kinase And Pseudokinase, Annabel T. Olson

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

Poxviruses employ sophisticated signaling pathways that thwart cellular defense mechanisms and simultaneously ensure viral factors are modulated properly. Yet, our understanding of these complex signaling networks are incomplete. For example, the vaccinia B1 kinase plays a vital role in inactivating the cellular antiviral factor BAF, and is suggested to orchestrate other pathways. B1 is highly conserved among poxviruses and exhibits a remarkable degree of similarity to VRKs, a family of cellular kinases, suggesting that the viral enzyme has evolved to mimic VRK activity. Indeed, B1 and VRKs have been demonstrated to target a shared substrate, the DNA binding protein BAF, …

A Human Papillomavirus-Independent Cervical Cancer Animal Model Reveals Unconventional Mechanisms Of Cervical Carcinogenesis, Chunbo He, Xiangmin Lv, Cong Huang, Peter C. Angeletti, Guohua Hua, Jixin Dong, Jin Zhou, Zhengfeng Wang, Bowen Ma, Xingcheng Chen, Paul F. Lambert, Bo R. Rueda, John S. Davis, Cheng Wang

Nebraska Center for Virology: Faculty Publications

HPV infections are common in healthy women and only rarely cause cervical cancer, suggesting that individual genetic susceptibility may play a critical role in the establishment of persistent HPV infection and the development of cervical cancer. Here, we provide convincing in vitro and in vivo evidence showing that differential expression and activation of YAP1 oncogene determine individual susceptibility to HPV infection and cervical carcinogenesis. We found that hyperactivation of YAP1 in mouse cervical epithelium was sufficient to induce invasive cervical cancer. Cervical epithelial cell-specific HPV16 E6/E7 and YAP1 double-knockin mouse model demonstrated that high-risk HPV synergized with hyperactivated YAP1 to …

Yap1-Lats2 Feedback Loop Dictates Senescent Or Malignant Cell Fate To Maintain Tissue Homeostasis, Chunbo He, Xiangmin Lv, Cong Huang, Guohua Hua, Bowen Ma, Xingcheng Chen, Peter C. Angeletti, Jixin Dong, Jin Zhou, Zhengfeng Wang, Bo R. Rueda, John S. Davis, Cheng Wang

Nebraska Center for Virology: Faculty Publications

Dysfunction of the homeostasis-maintaining systems in specific cell types or tissues renders the organism susceptible to a range of diseases, including cancers. One of the emerging mechanisms for maintaining tissue homeostasis is cellular senescence. Here, we report that the Hippo pathway plays a critical role in controlling the fate of ovarian cells. Hyperactivation of Yes-associated protein 1 (YAP1), the major effector of the Hippo pathway, induces senescence in cultured primary human ovarian surface epithelial cells (hOSEs). Large tumor suppressor 2 (LATS2), the primary upstream negative regulator of YAP1, is elevated in both YAP1-induced and natural replicative-triggered senescence. Deletion of LATS2 …

Design And Characterization Of A Consensus Hemagglutinin Vaccine Immunogen Against H3 Influenza A Viruses Of Swine, Haiyan Sun, Jung-Hyang Sur, Sarah Vitosh-Sillman, David J. Steffen, Hiep Vu

Nebraska Center for Virology: Faculty Publications

The substantial genetic diversity exhibited by influenza A viruses of swine (IAV-S) represents the main challenge for the development of a broadly protective vaccine against this important pathogen. The consensus vaccine immunogen has proven an effective vaccinology approach to overcome the extraordinary genetic diversity of RNA viruses. In this project, we sought to determine if a consensus IAV-S hemagglutinin (HA) immunogen would elicit broadly protective immunity in pigs. To address this question, a consensus HA gene (designated H3-CON.1) was generated from a set of 1,112 H3 sequences of IAV-S recorded in GenBank from 2011 to 2015. The consensus HA gene …

Development And Evaluation Of Vaccine Candidates For Senecavirus A, Bishwas Sharma

Electronic Theses and Dissertations

Senecavirus A (SVA) has been associated with several outbreaks of vesicular disease (VD) since 2014 in major swine-producing countries around the world. The virus causes VD that is clinically indistinguishable from foot-and-mouth disease (FMD) in pigs. Currently there are no commercial vaccines available for SVA. Here, we developed a live attenuated SVA strain by mutating a wild type SVA strain SD15-26 (wt SVA). The live attenuated virus, rSVA mSacII, replicated less efficiently in cell cultures in vitro and expressed lower amounts of VP1 and VP2 capsid proteins than wt SVA. Most importantly, the rSVA mSacII virus failed to induce clinical …

Nurse Practitioner Attitudes, Perceptions And Knowledge About Antimicrobial Stewardship, Evelyn C. Fabian

Walden Dissertations and Doctoral Studies

Resistance to antibiotics has increased dramatically in the United States, with serious associated medical, social, and economic consequences. The purpose of this project was to assess nurse practitioners' attitudes, perceptions, and knowledge about antimicrobial stewardship and knowledge in the management of anaerobic infections as well as resistant gram-negative bacteremia. Data were collected using a web-based survey in a hospital facility. The practice question explored whether nurse practitioners' attitudes, perceptions, and knowledge about antimicrobial stewardship significantly increased after an education program on antimicrobial stewardship. The project was framed by Knowles's adult learning theory. A 16-item survey was administered before and after …

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 …

A Poxvirus Pseudokinase Represses Viral Dna Replication Via A Pathway Antagonized By Its Paralog Kinase, Annabel T. Olson, Zhigang Wang, Amber B. Rico, Matthew S. Wiebe

Nebraska Center for Virology: Faculty Publications

Poxviruses employ sophisticated, but incompletely understood, signaling pathways that engage cellular defense mechanisms and simultaneously ensure viral factors are modulated properly. For example, the vaccinia B1 protein kinase plays a vital role in inactivating the cellular antiviral factor BAF, and likely orchestrates other pathways as well. In this study, we utilized experimental evolution of a B1 deletion virus to perform an unbiased search for suppressor mutations and identify novel pathways involving B1. After several passages of the ΔB1 virus we observed a robust increase in viral titer of the adapted virus. Interestingly, our characterization of the adapted viruses reveals that …

Near-Atomic Structure Of A Giant Virus, Qianglin Fang, Dongjie Zhu, Irina Agarkova, Jagat Adhikari, Thomas Klose, Yue Liu, Zhenguo Chen, Yingyuan Sun, Michael L. Gross, James L. Van Etten, Xinzheng Zhang, Michael G. Rossmann

Nebraska Center for Virology: Faculty Publications

Although the nucleocytoplasmic large DNA viruses (NCLDVs) are one of the largest group of viruses that infect many eukaryotic hosts, the near-atomic resolution structures of these viruses have remained unknown. Here we describe a 3.5 Å resolution icosahedrally averaged capsid structure of Paramecium bursaria chlorella virus 1 (PBCV-1). This structure consists of 5040 copies of the major capsid protein, 60 copies of the penton protein and 1800 minor capsid proteins of which there are 13 different types. The minor capsid proteins form a hexagonal network below the outer capsid shell, stabilizing the capsid by binding neighboring capsomers together. The size …

Relationship Between The Cervical Microbiome, Hiv Status, And Precancerous Lesions, Cameron Klein, Daniela Gonzalez, Kandali Samwel, Crispin Kahesa, Julius Mwaiselage, Nirosh Aluthge, Samodha Fernando, John T. West, Charles Wood, Peter C. Angeletti

Nebraska Center for Virology: Faculty Publications

Nearly all cervical cancers are causally associated with human papillomavirus (HPV). The burden of HPV-associated dysplasias in sub-Saharan Africa is influenced by HIV. To investigate the role of the bacterial microbiome in cervical dysplasia, cytobrush samples were collected directly from cervical lesions of 144 Tanzanian women. The V4 hypervariable region of the 16S rRNA gene was amplified and deep sequenced. Alpha diversity metrics (Chao1, PD whole tree, and operational taxonomic unit [OTU] estimates) displayed significantly higher bacterial richness in HIV-positive patients (P = 0.01) than in HIV-negative patients. In HIV-positive patients, there was higher bacterial richness in patients with …

Persistent Viral Reservoirs In Lymphoid Tissues In Siv-Infected Rhesus Macaques Of Chinese-Origin On Suppressive Antiretroviral Therapy, Summer Siddiqui, Stefanie Perez, Yong Gao, Lara Doyle-Meyers, Brian T. Foley, Qingsheng Li, Binhua Ling

Nebraska Center for Virology: Faculty Publications

Understanding HIV latent reservoirs in tissues is essential for the development of new strategies targeting these sites for eradication. Here, we assessed the size of latent reservoirs and the source of residual viruses in multiple lymphoid tissues of SIV-infected and fully suppressed rhesus macaques of Chinese-origin (cRMs). Eight cRMs were infected with SIVmac251 and treated with tenofovir and emtricitabine daily for 24 weeks initiated 4 weeks post-infection. Four of the eight animals reached sustained full viral suppression with undetectable viremia. The levels of cell-associated SIV DNA varied in peripheral blood mononuclear cells (PBMCs) and multiple lymphoid tissues, but with higher …

A Single-Cycle Adenovirus Type 7 Vaccine For Prevention Of Acute Respiratory Disease, Brianna L. Bullard, Brigette N. Corder, Eric A. Weaver

Nebraska Center for Virology: Faculty Publications

Adenovirus type 7 (Ad7) infection is associated with acute respiratory disease (ARD), especially in military recruits living in close quarters. Recently, several outbreaks of Ad7 infections have occurred in civilian populations, with some cases leading to death. However, the current Ad7 vaccine is licensed for use only in military recruits because it utilizes an orally delivered wild type virus which is shed in the stool for 28 days after immunization. This poses a safety risk due to the possibility of virus spread to vulnerable populations. To address the need for a safer Ad7 vaccine for use in civilian populations, we …

A Double Humanized Blt-Mice Model Featuring A Stable Human-Like Gut Microbiome And Human Immune System, Lance Daharsh, Jianshui Zhang, Amanda E. Ramer-Tait, Qingsheng Li

Nebraska Center for Virology: Faculty Publications

Humanized mice (hu-mice) that feature a functional human immune system have fundamentally changed the study of human pathogens and disease. They can be used to model diseases that are otherwise difficult or impossible to study in humans or other animal models. The gut microbiome can have a profound impact on human health and disease. However, the murine gut microbiome is very different than the one found in humans. There is a need for improved pre-clinical hu-mice models that have an engrafted human gut microbiome. Therefore, we created double hu-mice that feature both a human immune system and stable human-like gut …

The Vaccinia Virus (Vacv) B1 And Cellular Vrk2 Kinases Promote Vacv Replication Factory Formation Through Phosphorylation-Dependent Inhibition Of Vacv B12, Annabel T. Olson, Zhigang Wang, Annabel Olson, Alexandria C. Linville, Brianna L. Bullard, Eric A. Weaver, Clinton Jones, Matthew S. Wiebe

Nebraska Center for Virology: Faculty Publications

Comparative examination of viral and host protein homologs reveals novel mechanisms governing downstream signaling effectors of both cellular and vi- ral origin. The vaccinia virus B1 protein kinase is involved in promoting multiple facets of the virus life cycle and is a homolog of three conserved cellular enzymes called vaccinia virus-related kinases (VRKs). Recent evidence indicates that B1 and VRK2 mediate a com- mon pathway that is largely uncharacterized but appears independent of previous VRK substrates. Interestingly, separate studies described a novel role for B1 in inhibiting vac- cinia virus protein B12, which otherwise impedes an early event in the …