Life Sciences Commons^™

Diversity Of Trna Clusters In The Chloroviruses, Garry A. Duncan, David D. Dunigan Ph. D., James L. Van Etten

Nebraska Center for Virology: Faculty Publications

Viruses rely on their host’s translation machinery for the synthesis of their own proteins. Problems belie viral translation when the host has a codon usage bias (CUB) that is different from an infecting virus due to differences in the GC content between the host and virus genomes. Here, we examine the hypothesis that chloroviruses adapted to host CUB by acquisition and selection of tRNAs that at least partially favor their own CUB. The genomes of 41 chloroviruses comprising three clades, each infecting a different algal host, have been sequenced, assembled and annotated. All 41 viruses not only encode tRNAs, but …

A Decade In Review: A Systematic Review Of Universal Influenza Vaccines In Clinical Trials During The 2010 Decade, Brigette N. Corder, Brianna L. Bullard, Gregory Poland, Eric A. Weaver

Nebraska Center for Virology: Faculty Publications

On average, there are 3–5 million severe cases of influenza virus infections globally each year. Seasonal influenza vaccines provide limited protection against divergent influenza strains. Therefore, the development of a universal influenza vaccine is a top priority for the NIH. Here, we report a comprehensive summary of all universal influenza vaccines that were tested in clinical trials during the 2010–2019 decade. Of the 1597 studies found, 69 eligible clinical trials, which investigated 27 vaccines, were included in this review. Information from each trial was compiled for vaccine target, vaccine platform, adjuvant inclusion, clinical trial phase, and results. As we look …

Evaluation Of Antibody Response Directed Against Porcine Reproductive And Respiratory Syndrome Virus Structural Proteins, Hung Q. Luong, Huong T.L. Lai, Hiep L.X. Vu

Nebraska Center for Virology: Faculty Publications

Luciferase-immunoprecipitation system (LIPS), a liquid phase immunoassay, was used to evaluate antibody responses directed against the structural proteins of PRRSV in pigs that were experimentally infected with virulent PRRSV strains. First, the viral N protein was used as a model antigen to validate the assay. The LIPS results were highly comparable to that of the commercial IDEXX PRRS X3 ELISA. Subsequently, the assay was applied to simultaneously measure antibody reactivity against all eight structural proteins of PRRSV. The highest immunoreactivities were detected against GP3, M, and N proteins while the lowest reactivity was detected against ORF5a protein. Comparative analysis of …

Species D Adenoviruses As Oncolytic Viral Vectors, Brianna L. Bullard, Brigette N. Corder, Eric A. Weaver

Nebraska Center for Virology: Faculty Publications

Oncolytic adenoviruses (Ad) have shown promising results in the therapeutic treatment of cancer. Ad type 5 (Ad5) is the most extensively utilized Ad type. However, several limitations exist to using Ad5 as an oncolytic virus, including high levels of anti-Ad5 neutralizing antibodies in the population, binding of the Ad5 hexon to blood coagulation factor X leading to liver sequestration and toxicity, and reduced expression of the primary receptor CAR on many tumors. Here, we use in vitro methods to explore the oncolytic potential of four alternative Ad types (Ad26, 28, 45, and 48) belonging to the species D Ad subgroup …

Hiv-1 Subtypes And Drug Resistance Mutations Among Female Sex Workers Varied In Different Cities And Regions Of The Democratic Republic Of Congo, Eun Hee Kwon, Godefroid M. A. Musema, Jessica Boelter, Sydney Townsend, Desire Tshala-Katumbay, Patrick K. Kayembe, John T. West, Charles Wood

Nebraska Center for Virology: Faculty Publications

Background Complex mosaic structures of HIV-1 were found in the Democratic Republic of Congo (DRC). Currently, there is limited information on the circulating HIV-1 strains, the distribution of these strains and antiretroviral (ART) resistant viruses in different regions of the country, and the HIV-1 strains harbored by the high-risk groups like female sex workers (FSW) reported to be the source of recombinant and ART resistant viruses.

Methods Dried Blood Spots (DBS), collected from 325 infected FSWs in ten cities from 2012 DRC HIV/STI Integrated Biological and Behavioral Surveillance Survey, were tested for HIV-1 genotypes and antiretroviral resistance mutations. Regional segregation …

How The Cervical Microbiota Contributes To Cervical Cancer Risk In Sub-Saharan Africa, Cameron Klein, Crispin Kahesa, Julius Mwalselage, John T. West, Charles Wood, Peter C. Angeletti

Nebraska Center for Virology: Faculty Publications

Despite ongoing efforts, sub-Saharan Africa faces a higher cervical cancer burden than anywhere else in the world. Besides HPV infection, definitive factors of cervical cancer are still unclear. Particular states of the cervicovaginal microbiota and viral infections are associated with increased cervical cancer risk. Notably, HIV infection, which is prevalent in sub-Saharan Africa, greatly increases risk of cervicovaginal dysbiosis and cervical cancer. To better understand and address cervical cancer in sub-Saharan Africa, a better knowledge of the regional cervicovaginal microbiome is required This review establishes current knowledge of HPV, HIV, cervicovaginal infections, and the cervicovaginal microbiota in sub-Saharan Africa. Because …

The Kaposi’S Sarcoma-Associated Herpesvirus (Kshv) Gh/Gl Complex Is The Predominant Neutralizing Antigenic Determinant In Kshv-Infected Individuals, Yasaman Mortazavi, Salum J. Lidenge, Tara Tran, John T. West, Charles Wood, For Yue Tso

Nebraska Center for Virology: Faculty Publications

Kaposi’s sarcoma-associated herpesvirus (KSHV) is the etiological agent of Kaposi’s sarcoma (KS), one of the most prevalent cancers of people living with HIV/AIDS in sub-Saharan Africa. The seroprevalence for KSHV is high in the region, and no prophylactic vaccine against the virus is available. In this study, we characterized the antigenic targets of KSHV-specific neutralizing antibodies (nAbs) in asymptomatic KSHV-infected individuals and KS patients with high nAbs titers. We quantified the extent to which various KSHV envelope glycoproteins (gB, ORF28, ORF68, gH, gL, gM, gN and gpK8.1) adsorbed/removed KSHV-specific nAbs from the plasma of infected individuals. Our study revealed that …

Mycoplasma Co-Infection Is Associated With Cervical Cancer Risk, Cameron Klein, Kandali Samwel, Crispin Kahesa, Julius Mwaiselage, John T. West, Charles Wood, Peter C. Angeletti

Nebraska Center for Virology: Faculty Publications

Tanzania faces one of the highest cervical cancer burdens in the world. Recent work has suggested that the bacterial family Mycoplasmataceae is associated with higher levels of human papillomavirus (HPV), human immunodeficiency virus (HIV), and pre-cancerous cervical lesions. Mycoplasmataceae infection in Tanzania is not well understood, especially when considering the differences between sexually transmitted species of Mycoplasmataceae. To establish the prevalence of common Mycoplasmataceae cervical infections and evaluate their relationship with risk factors for cervical cancer, 1160 Tanzanian women responded to an epidemiological questionnaire and were tested for HIV, HPV, cervical lesions, Mycoplasma genitalium, Mycoplasma hominis, Ureaplasma spp., and Lactobacillus …

Incidence Of The Covid-19 In Iraq – Implications For Travellers, Maysaa Kadhim Al-Malkey, Maitham Ahmed Al-Sammak

Nebraska Center for Virology: Faculty Publications

The first emerged Coronavirus Disease 2019 (COVID-19) was in Wuhan, Hubei Province, China at the end of 2019, then spread to the rest of China [1], followed by the spread of the COVID-19 epidemics into the world caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) [2]. Many epidemiological assessments in different countries from Asia, Europe, and North America have been published [3]. Nevertheless, there are countries in the Middle East like Iraq, with a rapid increase in cases and a high number of deaths, with a lack of studies. It is worth noting that the Iraqi Foreign Ministry was …

Prevalence Of Kaposi's Sarcoma-Associated Herpesvirus And Transfusion-Transmissible Infections In Tanzanian Blood Donors, Salum J. Lidenge, Tara Tran, For Yue Tso, John R. Ngowi, Danielle M. Shea, Julius Mwaiselage, Charles Wood, John T. West

Nebraska Center for Virology: Faculty Publications

Objective: Kaposi's sarcoma-associated herpesvirus (KSHV) is the causative agent for Kaposi's sarcoma (KS), one of the most common cancers in Tanzania. We have investigated KSHV prevalence and factors associated with KSHV infection in Tanzania.

Methods: This is a cross-sectional study of voluntary blood-donors from Dar es Salaam, Tanzania. Plasma was screened for KSHV, HIV-1, HBV, HCV and Treponema pallidum (syphilis). Associations between KSHV sero-status and risk factors were analyzed. Odds ratios (OR) and 95% confidence intervals (CI) are reported to evaluate risk factors of KSHV infection. All tests were 2-tailed, and P-values <0.05 were considered statistically significant.

Results: The overall KSHV seroprevalence was 56.9%. Significantly …

Perivascular Macrophages In The Neonatal Macaque Brain Undergo Massive Necroptosis After Simian Immunodeficiency Virus Infection, Diana G. Bohannon, Yueying Wang, Colin H. Reinhart, Julian B. Hattler, Jiangtao Luo, Hamid R. Okhravi, Jianshui Zhang, Qingsheng Li, Marcelo J. Kuroda, Woong-Ki Kim

Nebraska Center for Virology: Faculty Publications

We previously showed that rhesus macaques neonatally infected with simian immunodeficiency virus (SIV) do not develop SIV encephalitis (SIVE) and maintain low brain viral loads despite having similar plasma viral loads compared to SIV-infected adults. We hypothesize that differences in myeloid cell populations that are the known target of SIV and HIV in the brain contribute to the lack of neonatal susceptibility to lentivirus-induced encephalitis. Using immunohistochemistry and immunofluorescence microscopy, we examined the frontal cortices from uninfected and SIV-infected infant and adult macaques (n = 8/ea) as well as adults with SIVE (n = 4) to determine differences in myeloid …

Lack Of Cd8+ T-Cell Co-Localization With Kaposi’S Sarcoma- Associated Herpesvirus Infected Cells In Kaposi’S Sarcoma Tumors, Salum J. Lidenge, For Yue Tso, Owen Ngalamika, Jaydeep Kolape, John R. Ngowi, Julius Mwaiselage, Charles Wood, John T. West

Nebraska Center for Virology: Faculty Publications

Despite the close association between Kaposi’s sarcoma (KS) and immune dysfunction, it remains unclear whether tumor infiltrating immune cells (TIIC), by their absence, presence, or dysfunction, are mechanistically correlated with KS pathogenesis. Therefore, their potential capacity to serve as prognostic biomarkers of KS disease progression or control is unclear. Because epidemic-KS (EpKS) occurs with HIV-1 co-infection, it is particularly important to compare TIIC between EpKS and HIV-negative African endemic-KS (EnKS) to dissect the roles of HIV-1 and Kaposi Sarcoma-associated herpesvirus (KSHV) in KS pathogenesis. This cross-sectional study of 13 advanced KS (4 EnKS, 9 EpKS) patients and 3 healthy controls …

Epstein Barr Virus-Immortalizedｂlymphocytes Exacerbate Experimental Autoimmune Encephalomyelitis In Xenograft Mice, Pascal Polepole, Alison Bartenslager, Yutong Liu, Thomas M. Petro, Samodha C. Fernando, Luwen Zhang

Nebraska Center for Virology: Faculty Publications

Multiple sclerosis (MS) is the most common autoimmune disorder affecting the central nervous system. Epstein-Barr virus (EBV) is a causative agent for infectious mononucleosis (IM) that is associated with MS pathogenesis. However, the exact mechanism by which EBV, specifically in IM, increases the risk for MS remains unknown. EBV immortalizes primary B lymphocytes in vitro and causes excessive B lymphocyte proliferation in IM in vivo. In asymptomatic carriers, EBV-infected B lymphocytes still proliferate to certain degrees, the process of which is tightly controlled by the host immune systems. Experimental autoimmune encephalomyelitis (EAE) mimics key features of MS in humans and …

Genetic Diversity Of Potassium Ion Channel Proteins Encoded By Chloroviruses That Infect Chlorella Heliozoae, Carter Murry, Irina V. Agarkova, Jayadri S. Ghosh, Fiona C. Fitzgerald, Roger M. Carlson, Brigitte Hertel, Kerri Kukovetz, Oliver Rauh, Gerhard Thiel, James L. Van Etten

Nebraska Center for Virology: Faculty Publications

Chloroviruses are large, plaque-forming, dsDNA viruses that infect chlorella-like green algae that live in a symbiotic relationship with protists. Chloroviruses have genomes from 290 to 370 kb, and they encode as many as 400 proteins. One interesting feature of chloroviruses is that they encode a potassium ion (K+) channel protein named Kcv. The Kcv protein encoded by SAG chlorovirus ATCV-1 is one of the smallest known functional K+ channel proteins consisting of 82 amino acids. The KcvATCV-1 protein has similarities to the family of two transmembrane domain K+ channel proteins; it consists of two transmembrane -helixes with a pore region …

Viral And Immunological Analytes Are Poor Predictors Of The Clinical Treatment Response In Kaposi’S Sarcoma Patients, Salum J. Lidenge, For Yue Tso, Yasaman Mortazavi, John R. Ngowi, Danielle M. Shea, Julius Mwaiselage, Charles Wood, John T. West

Nebraska Center for Virology: Faculty Publications

Kaposi’s sarcoma-associated herpes virus (KSHV) is the etiologic agent for Kaposi’s sarcoma (KS). The prognostic utility of KSHV and HIV-1 (human immunodeficiency virus) viremia as well as immunological parameters in clinical management of participants with KS is unclear. The objective of this study was to investigate viral and immunological parameters as predictors of KS treatment responses in participants with KS from sub-Saharan Africa (SSA). Plasma KSHV-DNA, HIV-1 viral load, total anti-KSHV antibody, KSHV-neutralizing antibody (nAb), cytokine/chemokine levels, and T-cell differentiation subsets were quantified before and after KS treatment in 13 participants with KS and in 13 KSHV-infected asymptomatic control individuals. …

Chloroviruses, James L. Van Etten, Irina V. Agarkova, David D. Dunigan

Nebraska Center for Virology: Faculty Publications

Chloroviruses are large dsDNA, plaque-forming viruses that infect certain chlorella-like green algae; the algae are normally mutualistic endosymbionts of protists and metazoans and are often referred to as zoochlorellae. The viruses are ubiquitous in inland aqueous environments throughout the world and occasionally single types reach titers of thousands of plaque-forming units per ml of native water. The viruses are icosahedral in shape with a spike structure located at one of the vertices. They contain an internal membrane that is required for infectivity. The viral genomes are 290 to 370 kb in size, which encode up to 16 tRNAs and 330 …

Genome-Wide Variation In Potyviruses, Deepti Nigam, Katherine Latourrette, Pedro F.N. Souza, Hernan Garcia Ruiz

Nebraska Center for Virology: Faculty Publications

Potyviruses (family Potyviridae, genus Potyvirus) are the result of an initial radiation event that occurred 6,600 years ago. The genus currently consists of 167 species that infect monocots or dicots, including domesticated and wild plants. Potyviruses are transmitted in a non-persistent way by more than 200 species of aphids. As indicated by their wide host range, worldwide distribution, and diversity of their vectors, potyviruses have an outstanding capacity to adapt to new hosts and environments. However, factors that confer adaptability are poorly understood. Viral RNA-dependent RNA polymerases introduce nucleotide substitutions that generate genetic diversity. We hypothesized that selection imposed by …

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 …

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, …

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. …

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 …

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 …

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 …

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 …

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 …

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 …

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 …