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Medical Immunology

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Full-Text Articles in Medicine and Health Sciences

Gut Microbial Dysbiosis Differs In Two Distinct Cachectic Tumor-Bearing Models Consuming The Same Diet, Lauri O. Byerley, Brittany Lorenzen, Hsiao Man Chang, William G. Hartman, Michael J. Keenan, Ryan Page, Meng Luo, Scot E. Dowd, Christopher M. Taylor Apr 2024

Gut Microbial Dysbiosis Differs In Two Distinct Cachectic Tumor-Bearing Models Consuming The Same Diet, Lauri O. Byerley, Brittany Lorenzen, Hsiao Man Chang, William G. Hartman, Michael J. Keenan, Ryan Page, Meng Luo, Scot E. Dowd, Christopher M. Taylor

School of Medicine Faculty Publications

The impact of cancer cachexia on the colonic microbiota is poorly characterized. This study assessed the effect of two cachectic-producing tumor types on the gut microbiota to determine if a similar dysbiosis could be found. In addition, it was determined if a diet containing an immunonutrient-rich food (walnuts) known to promote the growth of probiotic bacteria in the colon could alter the dysbiosis and slow cachexia. Male Fisher 344 rats were randomly assigned to a semi-purified diet with or without walnuts. Then, within each diet group, rats were further assigned randomly to a treatment group: tumor-bearing ad libitum fed (TB), …

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Covid-19 Vaccination In Patients With Inborn Errors Of Immunity Reduces Hospitalization And Critical Care Needs Related To Covid-19: A Usidnet Report, John Mcdonnell, Kimberley Cousins, M. Elizabeth M. Younger, Adam Lane, Hassan Abolhassani, Roshini S. Abraham, Salem Al-Tamemi, Juan Carlos Aldave-Becerra, Eman Hesham Al-Faris, Alberto Alfaro-Murillo, Suzan A. Alkhater, Nouf Alsaati, Alexa Michelle Altman Doss, Melissa Anderson, Ernestina Angarola, Barbara Ariue, Danielle E. Arnold, Amal H. Assa'ad, Caner Aytekin, Meaghan Bank, Jenna R.E. Bergerson, Jack Bleesing, John Boesing, Carolina Bouso, Nicholas Brodszki, Diana Cabanillas, Carol Cady, Meghan A. Callahan, Luke Wall, Et Al Apr 2024

Covid-19 Vaccination In Patients With Inborn Errors Of Immunity Reduces Hospitalization And Critical Care Needs Related To Covid-19: A Usidnet Report, John Mcdonnell, Kimberley Cousins, M. Elizabeth M. Younger, Adam Lane, Hassan Abolhassani, Roshini S. Abraham, Salem Al-Tamemi, Juan Carlos Aldave-Becerra, Eman Hesham Al-Faris, Alberto Alfaro-Murillo, Suzan A. Alkhater, Nouf Alsaati, Alexa Michelle Altman Doss, Melissa Anderson, Ernestina Angarola, Barbara Ariue, Danielle E. Arnold, Amal H. Assa'ad, Caner Aytekin, Meaghan Bank, Jenna R.E. Bergerson, Jack Bleesing, John Boesing, Carolina Bouso, Nicholas Brodszki, Diana Cabanillas, Carol Cady, Meghan A. Callahan, Luke Wall, Et Al

School of Medicine Faculty Publications

BACKGROUND: The CDC and ACIP recommend COVID-19 vaccination for patients with inborn errors of immunity (IEI). Not much is known about vaccine safety in IEI, and whether vaccination attenuates infection severity in IEI. OBJECTIVE: To estimate COVID-19 vaccination safety and examine effect on outcomes in patients with IEI. METHODS: We built a secure registry database in conjunction with the US Immunodeficiency Network to examine vaccination frequency and indicators of safety and effectiveness in IEI patients. The registry opened on January 1, 2022, and closed on August 19, 2022. RESULTS: Physicians entered data on 1245 patients from 24 countries. The most …

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Momkk1 And Moatg1 Dichotomously Regulating Autophagy And Pathogenicity Through Moatg9 Phosphorylation In Magnaporthe Oryzae, Yun Kong, Pusheng Guo, Jiayun Xu, Jiaxu Li, Miao Wu, Ziqi Zhang, Yifan Wang, Xinyu Liu, Leiyun Yang, Muxing Liu, Haifeng Zhang, Ping Wang, Zhengguang Zhang Mar 2024

Momkk1 And Moatg1 Dichotomously Regulating Autophagy And Pathogenicity Through Moatg9 Phosphorylation In Magnaporthe Oryzae, Yun Kong, Pusheng Guo, Jiayun Xu, Jiaxu Li, Miao Wu, Ziqi Zhang, Yifan Wang, Xinyu Liu, Leiyun Yang, Muxing Liu, Haifeng Zhang, Ping Wang, Zhengguang Zhang

School of Medicine Faculty Publications

Autophagy is a central biodegradation pathway critical in eliminating intracellular cargo to maintain cellular homeostasis and improve stress resistance. At the same time, the key component of the mitogen-activated protein kinase cascade regulating cell wall integrity signaling MoMkk1 has an essential role in the autophagy of the rice blast fungus Magnaporthe oryzae. Still, the mechanism of how MoMkk1 regulates autophagy is unclear. Interestingly, we found that MoMkk1 regulates the autophagy protein MoAtg9 through phosphorylation. MoAtg9 is a transmembrane protein subjected to phosphorylation by autophagy-related protein kinase MoAtg1. Here, we provide evidence demonstrating that MoMkk1-dependent MoAtg9 phosphorylation is required for phospholipid …

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Microbial Interactions Among Gardnerella, Prevotella And Fannyhessea Prior To Incident Bacterial Vaginosis: Protocol For A Prospective, Observational Study, Christina A. Muzny, Jacob H. Elnaggar, Lúcia G.V. Sousa, Ângela Lima, Kristal J. Aaron, Isaac C. Eastlund, Keonte J. Graves, Chaoling Dong, Olivia T. Van Gerwen, Meng Luo, Ashutosh Tamhane, Dustin Long, Nuno Cerca, Christopher M. Taylor Feb 2024

Microbial Interactions Among Gardnerella, Prevotella And Fannyhessea Prior To Incident Bacterial Vaginosis: Protocol For A Prospective, Observational Study, Christina A. Muzny, Jacob H. Elnaggar, Lúcia G.V. Sousa, Ângela Lima, Kristal J. Aaron, Isaac C. Eastlund, Keonte J. Graves, Chaoling Dong, Olivia T. Van Gerwen, Meng Luo, Ashutosh Tamhane, Dustin Long, Nuno Cerca, Christopher M. Taylor

School of Graduate Studies Faculty Publications

Introduction The aetiology of bacterial vaginosis (BV), a biofilm-associated vaginal infection, remains unknown. Epidemiologic data suggest that it is sexually transmitted. BV is characterised by loss of lactic acid-producing lactobacilli and an increase in facultative and strict anaerobic bacteria. Gardnerella spp are present in 95%–100% of cases; Gardnerella vaginalis has been found to be more virulent than other BV-associated bacteria (BVAB) in vitro. However, G. vaginalis is found in women with normal vaginal microbiota and colonisation is not sufficient for BV development. We hypothesise that Gardnerella spp initiate BV biofilm formation, but incident BV (iBV) requires incorporation of other key …

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Autophagy And Cell Wall Integrity Pathways Coordinately Regulate The Development And Pathogenicity Through Moatg4 Phosphorylation In Magnaporthe Oryzae, Pusheng Guo, Yurong Wang, Jiayun Xu, Zhixiang Yang, Ziqi Zhang, Jinyi Qian, Jiexiong Hu, Ziyi Yin, Leiyun Yang, Muxing Liu, Xinyu Liu, Gang Li, Haifeng Zhang, Ryan Rumsey, Ping Wang, Zhengguang Zhang Jan 2024

Autophagy And Cell Wall Integrity Pathways Coordinately Regulate The Development And Pathogenicity Through Moatg4 Phosphorylation In Magnaporthe Oryzae, Pusheng Guo, Yurong Wang, Jiayun Xu, Zhixiang Yang, Ziqi Zhang, Jinyi Qian, Jiexiong Hu, Ziyi Yin, Leiyun Yang, Muxing Liu, Xinyu Liu, Gang Li, Haifeng Zhang, Ryan Rumsey, Ping Wang, Zhengguang Zhang

School of Medicine Faculty Publications

Autophagy and Cell wall integrity (CWI) signaling are critical stress-responsive processes during fungal infection of host plants. In the rice blast fungus Magnaporthe oryzae, autophagy-related (ATG) proteins phosphorylate CWI kinases to regulate virulence; however, how autophagy interplays with CWI signaling to coordinate such regulation remains unknown. Here, we have identified the phosphorylation of ATG protein MoAtg4 as an important process in the coordination between autophagy and CWI in M. oryzae. The ATG kinase MoAtg1 phosphorylates MoAtg4 to inhibit the deconjugation and recycling of the key ATG protein MoAtg8. At the same time, MoMkk1, a core kinase of CWI, also phosphorylates …

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Targeted Repression Of Topa By Crispri Reveals A Critical Function For Balanced Dna Topoisomerase I Activity In The Chlamydia Trachomatis Developmental Cycle, Li Shen, Leiqiong Gao, Abigail R. Swoboda, Scot P. Ouellette Jan 2024

Targeted Repression Of Topa By Crispri Reveals A Critical Function For Balanced Dna Topoisomerase I Activity In The Chlamydia Trachomatis Developmental Cycle, Li Shen, Leiqiong Gao, Abigail R. Swoboda, Scot P. Ouellette

School of Medicine Faculty Publications

Chlamydia trachomatis is an obligate intracellular bacterium that is responsible for the most prevalent bacterial sexually transmitted infection. Changes in DNA topology in this pathogen have been linked to its pathogenicity-associated developmental cycle. Here, evidence is provided that the balanced activity of DNA topoisomerases contributes to controlling Chlamydia developmental processes. Utilizing catalytically inactivated Cas12 (dCas12)-based clustered regularly interspaced short palindromic repeats interference (CRISPRi) technology, we demonstrate targeted knockdown of chromosomal topA transcription in C. trachomatis without detected toxicity of dCas12. Repression of topA impaired the developmental cycle of C. trachomatis mostly through disruption of its differentiation from a replicative form …

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Interplay Between Acetylation And Ubiquitination Of Imitation Switch Chromatin Remodeler Isw1 Confers Multidrug Resistance In Cryptococcus Neoformans, Yang Meng, Yue Ni, Zhuoran Li, Tianhang Jiang, Tianshu Sun, Yanjian Li, Xindi Gao, Hailong Li, Chenhao Suo, Chao Li, Sheng Yang, Tian Lan, Guojian Liao, Tongbao Liu, Ping Wang, Chen Ding Jan 2024

Interplay Between Acetylation And Ubiquitination Of Imitation Switch Chromatin Remodeler Isw1 Confers Multidrug Resistance In Cryptococcus Neoformans, Yang Meng, Yue Ni, Zhuoran Li, Tianhang Jiang, Tianshu Sun, Yanjian Li, Xindi Gao, Hailong Li, Chenhao Suo, Chao Li, Sheng Yang, Tian Lan, Guojian Liao, Tongbao Liu, Ping Wang, Chen Ding

School of Medicine Faculty Publications

Cryptococcus neoformans poses a threat to human health, but anticryptococcal therapy is hampered by the emergence of drug resistance, whose underlying mechanisms remain poorly understood. Herein, we discovered that Isw1, an imitation switch chromatin remodeling ATPase, functions as a master modulator of genes responsible for in vivo and in vitro multidrug resistance in C. neoformans. Cells with the disrupted ISW1 gene exhibited profound resistance to multiple antifungal drugs. Mass spectrometry analysis revealed that Isw1 is both acetylated and ubiquitinated, suggesting that an interplay between these two modification events exists to govern Isw1 function. Mutagenesis studies of acetylation and ubiquitination sites …

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Hypoxia-Adenosine Axis As Therapeutic Targets For Acute Respiratory Distress Syndrome, Katherine Figarella, Jieun Kim, Wei Ruan, Tingting Mills, Holger Klaus Eltzschig, Xiaoyi Yuan Jan 2024

Hypoxia-Adenosine Axis As Therapeutic Targets For Acute Respiratory Distress Syndrome, Katherine Figarella, Jieun Kim, Wei Ruan, Tingting Mills, Holger Klaus Eltzschig, Xiaoyi Yuan

Journal Articles

The human respiratory and circulatory systems collaborate intricately to ensure oxygen delivery to all cells, which is vital for ATP production and maintaining physiological functions and structures. During limited oxygen availability, hypoxia-inducible factors (HIFs) are stabilized and play a fundamental role in maintaining cellular processes for hypoxia adaptation. First discovered during investigations of erythropoietin production regulation, HIFs influence physiological and pathological processes, including development, inflammation, wound healing, and cancer. HIFs promote extracellular adenosine signaling by enhancing adenosine generation and receptor signaling, representing an endogenous feedback mechanism that curbs excessive inflammation, supports injury resolution, and enhances hypoxia tolerance. This is especially …

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Genital Tract Infections, The Vaginal Microbiome And Gestational Age At Birth Among Pregnant Women In South Africa: A Cohort Study Protocol, Ranjana M.S. Gigi, Mandisa M. Mdingi, Hyunsul Jung, Shantelle Claassen-Weitz, Lukas Bütikofer, Jeffrey D. Klausner, Christina A. Muzny, Christopher M. Taylor, Janneke H.H.M. Van De Wijgert, Remco P.H. Peters, Nicola Low Dec 2023

Genital Tract Infections, The Vaginal Microbiome And Gestational Age At Birth Among Pregnant Women In South Africa: A Cohort Study Protocol, Ranjana M.S. Gigi, Mandisa M. Mdingi, Hyunsul Jung, Shantelle Claassen-Weitz, Lukas Bütikofer, Jeffrey D. Klausner, Christina A. Muzny, Christopher M. Taylor, Janneke H.H.M. Van De Wijgert, Remco P.H. Peters, Nicola Low

School of Medicine Faculty Publications

Introduction Preterm birth complications are the most common cause of death in children under 5 years. The presence of multiple microorganisms and genital tract inflammation could be the common mechanism driving early onset of labour. South Africa has high levels of preterm birth, genital tract infections and HIV infection among pregnant women. We plan to investigate associations between the presence of multiple lower genital tract microorganisms in pregnancy and gestational age at birth. Methods and analysis This cohort study enrols around 600 pregnant women at one public healthcare facility in East London, South Africa. Eligible women are ≥18 years and …

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Association Of Chlamydia Trachomatis Burden With The Vaginal Microbiota, Bacterial Vaginosis, And Metronidazole Treatment, Caleb M. Ardizzone, Christopher M. Taylor, Evelyn Toh, Rebecca A. Lillis, Jacob H. Elnaggar, John W. Lammons, Patricia Dehon Mott, Emily L. Duffy, Li Shen, Alison J. Quayle Dec 2023

Association Of Chlamydia Trachomatis Burden With The Vaginal Microbiota, Bacterial Vaginosis, And Metronidazole Treatment, Caleb M. Ardizzone, Christopher M. Taylor, Evelyn Toh, Rebecca A. Lillis, Jacob H. Elnaggar, John W. Lammons, Patricia Dehon Mott, Emily L. Duffy, Li Shen, Alison J. Quayle

School of Graduate Studies Faculty Publications

Bacterial vaginosis (BV), a dysbiosis of the vaginal microbiota, is a common coinfection with Chlamydia trachomatis (Ct), and BV-associated bacteria (BVAB) and their products have been implicated in aiding Ct evade natural immunity. Here, we determined if a non-optimal vaginal microbiota was associated with a higher genital Ct burden and if metronidazole, a standard treatment for BV, would reduce Ct burden or aid in natural clearance of Ct infection. Cervicovaginal samples were collected from women at enrollment and, if testing positive for Ct infection, at a follow-up visit approximately one week later. Cervical Ct burden was assessed by inclusion forming …

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Sutterella And Its Metabolic Pathways Positively Correlate With Vaccine-Elicited Antibody Responses In Infant Rhesus Macaques, Danting Jiang, Ria Goswami, Maria Dennis, Holly Heimsath, Pamela A. Kozlowski, Amir Ardeshir, Koen K.A. Van Rompay, Kristina De Paris, Sallie R. Permar, Neeraj K. Surana Dec 2023

Sutterella And Its Metabolic Pathways Positively Correlate With Vaccine-Elicited Antibody Responses In Infant Rhesus Macaques, Danting Jiang, Ria Goswami, Maria Dennis, Holly Heimsath, Pamela A. Kozlowski, Amir Ardeshir, Koen K.A. Van Rompay, Kristina De Paris, Sallie R. Permar, Neeraj K. Surana

School of Graduate Studies Faculty Publications

Introduction: It is becoming clearer that the microbiota helps drive responses to vaccines; however, little is known about the underlying mechanism. In this study, we aimed to identify microbial features that are associated with vaccine immunogenicity in infant rhesus macaques. Methods: We analyzed 16S rRNA gene sequencing data of 215 fecal samples collected at multiple timepoints from 64 nursery-reared infant macaques that received various HIV vaccine regimens. PERMANOVA tests were performed to determine factors affecting composition of the gut microbiota throughout the first eight months of life in these monkeys. We used DESeq2 to identify differentially abundant bacterial taxa, PICRUSt2 …

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Lactic Acid Bacterial Surface Display Of Scytovirin Inhibitors For Anti-Ebolavirus Infection, Joshua Wiggins, Ngan Nguyen, Wenzhong Wei, Leah Liu Wang, Haley Hollingsead Olson, Shi-Hua Xiang Nov 2023

Lactic Acid Bacterial Surface Display Of Scytovirin Inhibitors For Anti-Ebolavirus Infection, Joshua Wiggins, Ngan Nguyen, Wenzhong Wei, Leah Liu Wang, Haley Hollingsead Olson, Shi-Hua Xiang

Nebraska Center for Virology: Faculty Publications

Scytovirin (SVN) is a lectin from cyanobacteria which has a strong inhibitory activity against Ebola virus infection. We engineered scytovirin as the inhibitor for surface display of lactic acid bacteria to block Ebola virus infection. Two different bacterial strains (Lactobacillus casei and Lactococcus lactis) were successfully engineered for scytovirin expression on the bacterial surface. These bacteria were found to be effective at neutralizing pseudotyped Ebolavirus in a cell-based assay. This approach can be utilized for prophylactic prevention, as well as for treatment. Since lactic acid bacteria can colonize the human body, a long-term efficacy could be achieved. Furthermore, …

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Dynamics Of Serum-Neutralizing Antibody Responses In Vaccinees Through Multiple Doses Of The Bnt162b2 Vaccine, Jared Sheehan, Caleb M. Ardizzone, Mayank Khanna, Amber J. Trauth, Michael E. Hagensee, Alistair J. Ramsay Nov 2023

Dynamics Of Serum-Neutralizing Antibody Responses In Vaccinees Through Multiple Doses Of The Bnt162b2 Vaccine, Jared Sheehan, Caleb M. Ardizzone, Mayank Khanna, Amber J. Trauth, Michael E. Hagensee, Alistair J. Ramsay

School of Graduate Studies Faculty Publications

SARS-CoV-2 mRNA vaccines are administered as effective prophylactic measures for reducing virus transmission rates and disease severity. To enhance the durability of post-vaccination immunity and combat SARS-CoV-2 variants, boosters have been administered to two-dose vaccinees. However, long-term humoral responses following booster vaccination are not well characterized. A 16-member cohort of healthy SARS-CoV-2 naïve participants were enrolled in this study during a three-dose BNT162b2 vaccine series. Serum samples were collected from vaccinees over 420 days and screened for antigen (Ag)-specific antibody titers, IgG subclass distribution, and neutralizing antibody (nAb) responses. Vaccine boosting restored peak Ag-specific titers with sustained α-RBD IgG and …

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Comparative Analysis Of Swine Antibody Responses Following Vaccination With Live-Attenuated And Killed African Swine Fever Virus Vaccines, Hung Q. Luong, Huong T. L. Lai, Lam Q. Truong, The N. Nguyen, Hanh D. Vu, Hoa T. Nguyen, Lan T. Nguyen, Trang H. Pham, David Scott Mcvey, Hiep Vu Nov 2023

Comparative Analysis Of Swine Antibody Responses Following Vaccination With Live-Attenuated And Killed African Swine Fever Virus Vaccines, Hung Q. Luong, Huong T. L. Lai, Lam Q. Truong, The N. Nguyen, Hanh D. Vu, Hoa T. Nguyen, Lan T. Nguyen, Trang H. Pham, David Scott Mcvey, Hiep Vu

Nebraska Center for Virology: Faculty Publications

African swine fever virus (ASFV) is circulating in many swine-producing countries, causing significant economic losses. It is observed that pigs experimentally vaccinated with a live-attenuated virus (LAV) but not a killed virus (KV) vaccine develop solid homologous protective immunity. The objective of this study was to comparatively analyze antibody profiles between pigs vaccinated with an LAV vaccine and those vaccinated with a KV vaccine to identify potential markers of vaccineinduced protection. Thirty ASFV seronegative pigs were divided into three groups: Group 1 received a single dose of an experimental LAV, Group 2 received two doses of an experimental KV vaccine, …

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In Vivo Treatment With Insulin-Like Growth Factor 1 Reduces Ccr5 Expression On Vaccine-Induced Activated Cd4+ T-Cells, Massimiliano Bissa, Veronica Galli, Luca Schifanella, Monica Vaccari, Mohammad Arif Rahman, Giacomo Gorini, Nicolò Binello, Sarkis Sarkis, Anna Gutowska, Isabela Silva De Castro, Melvin N. Doster, Ramona Moles, Guido Ferrari, Xiaoying Shen, Georgia D. Tomaras, David C. Montefiori, Kombo F. N’Guessan, Dominic Paquin-Proulx, Pamela A. Kozlowski, David J. Venzon, Hyoyoung Choo-Wosoba, Matthew W. Breed, Joshua Kramer, Genoveffa Franchini Oct 2023

In Vivo Treatment With Insulin-Like Growth Factor 1 Reduces Ccr5 Expression On Vaccine-Induced Activated Cd4+ T-Cells, Massimiliano Bissa, Veronica Galli, Luca Schifanella, Monica Vaccari, Mohammad Arif Rahman, Giacomo Gorini, Nicolò Binello, Sarkis Sarkis, Anna Gutowska, Isabela Silva De Castro, Melvin N. Doster, Ramona Moles, Guido Ferrari, Xiaoying Shen, Georgia D. Tomaras, David C. Montefiori, Kombo F. N’Guessan, Dominic Paquin-Proulx, Pamela A. Kozlowski, David J. Venzon, Hyoyoung Choo-Wosoba, Matthew W. Breed, Joshua Kramer, Genoveffa Franchini

School of Graduate Studies Faculty Publications

At the heart of the DNA/ALVAC/gp120/alum vaccine’s efficacy in the absence of neutralizing antibodies is a delicate balance of pro- and anti-inflammatory immune responses that effectively decreases the risk of SIVmac251 acquisition in macaques. Vaccine efficacy is linked to antibodies recognizing the V2 helical conformation, DC-10 tolerogenic dendritic cells eliciting the clearance of apoptotic cells via efferocytosis, and CCR5 downregulation on vaccine-induced gut homing CD4+ cells. RAS activation is also linked to vaccine efficacy, which prompted the testing of IGF-1, a potent inducer of RAS activation with vaccination. We found that IGF-1 changed the hierarchy of V1/V2 epitope recognition and …

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Simian Immunodeficiency Virus-Infected Rhesus Macaques With Aids Co-Develop Cardiovascular Pathology And Encephalitis, Kevin S. White, Joshua A. Walker, John Wang, Patrick Autissier, Andrew D. Miller, Nadia N. Abuelezan, Rachel Burrack, Qingsheng Li, Woong-Ki Kim, Kenneth C. Williams Oct 2023

Simian Immunodeficiency Virus-Infected Rhesus Macaques With Aids Co-Develop Cardiovascular Pathology And Encephalitis, Kevin S. White, Joshua A. Walker, John Wang, Patrick Autissier, Andrew D. Miller, Nadia N. Abuelezan, Rachel Burrack, Qingsheng Li, Woong-Ki Kim, Kenneth C. Williams

Nebraska Center for Virology: Faculty Publications

Despite effective antiretroviral therapy, HIV co-morbidities remain where central nervous system (CNS) neurocognitive disorders and cardiovascular disease (CVD)-pathology that are linked with myeloid activation are most prevalent. Comorbidities such as neurocogntive dysfunction and cardiovascular disease (CVD) remain prevalent among people living with HIV. We sought to investigate if cardiac pathology (inflammation, fibrosis, cardiomyocyte damage) and CNS pathology (encephalitis) develop together during simian immunodeficiency virus (SIV) infection and if their co-development is linked with monocyte/ macrophage activation. We used a cohort of SIV-infected rhesus macaques with rapid AIDS and demonstrated that SIV encephalitis (SIVE) and CVD pathology occur together more frequently …

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Co-Infection And Co-Localization Of Kaposi Sarcoma-Associated Herpesvirus And Epstein-Barr Virus In Hiv-Associated Kaposi Sarcoma: A Case Report, Peter Julius, Guobin Guobin, Stepfanie Siyumbwa, Jane Musumali, For Yue Tso, Owen Ngalamika, Trevor Kaile, Fred Maate, Phyllis Moonga, John T. West, Peter Angeletti, Charles Wood Oct 2023

Co-Infection And Co-Localization Of Kaposi Sarcoma-Associated Herpesvirus And Epstein-Barr Virus In Hiv-Associated Kaposi Sarcoma: A Case Report, Peter Julius, Guobin Guobin, Stepfanie Siyumbwa, Jane Musumali, For Yue Tso, Owen Ngalamika, Trevor Kaile, Fred Maate, Phyllis Moonga, John T. West, Peter Angeletti, Charles Wood

Nebraska Center for Virology: Faculty Publications

Kaposi sarcoma (KS), a multifocal vascular neoplasm frequently observed in HIVpositive individuals, primarily affects the skin, mucous membranes, visceral organs, and lymph nodes. KS is associated primarily with Kaposi sarcomaassociated herpesvirus (KSHV) infection. In this case report, we present a rare occurrence of co-infection and co-localization of KSHV and Epstein-Barr virus (EBV) in KS arising from the conjunctiva, which, to our knowledge, has not been reported previously. Immunohistochemistry (IHC), DNA polymerase chain reaction (PCR), and EBV-encoded RNA in situ hybridization (EBER-ISH) were utilized to demonstrate the presence of KSHV and EBV infection in the ocular KS lesion. Nearly all KSHV-positive …

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A Single-Dose Intramuscular Immunization Of Pigs With Lipid Nanoparticle Dna Vaccines Based On The Hemagglutinin Antigen Confers Complete Protection Against Challenge Infection With The Homologous Influenza Virus Strain, The N. Nguyen, Sushmita Kumari, Sarah Vitosh-Sillman, Jayeshbhai Chaudhari, Danh C. Lai, Hiep Vu Oct 2023

A Single-Dose Intramuscular Immunization Of Pigs With Lipid Nanoparticle Dna Vaccines Based On The Hemagglutinin Antigen Confers Complete Protection Against Challenge Infection With The Homologous Influenza Virus Strain, The N. Nguyen, Sushmita Kumari, Sarah Vitosh-Sillman, Jayeshbhai Chaudhari, Danh C. Lai, Hiep Vu

Nebraska Center for Virology: Faculty Publications

The Influenza A virus of swine (IAV-S) is highly prevalent and causes significant economic losses to swine producers. Due to the highly variable and rapidly evolving nature of the virus, it is critical to develop a safe and versatile vaccine platform that allows for frequent updates of the vaccine immunogens to cope with the emergence of new viral strains. The main objective of this study was to assess the feasibility of using lipid nanoparticles (LNPs) as nanocarriers for delivering DNA plasmid encoding the viral hemagglutinin (HA) gene in pigs. The intramuscular administration of a single dose of the LNP-DNA vaccines …

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Existing Evidence For Influenza B Virus Adaptations To Drive Replication In Humans As The Primary Host, Matthew J. Pekarek, Eric A. Weaver Sep 2023

Existing Evidence For Influenza B Virus Adaptations To Drive Replication In Humans As The Primary Host, Matthew J. Pekarek, Eric A. Weaver

Nebraska Center for Virology: Faculty Publications

Influenza B virus (IBV) is one of the two major types of influenza viruses that circulate each year. Unlike influenza A viruses, IBV does not harbor pandemic potential due to its lack of historical circulation in non-human hosts. Many studies and reviews have highlighted important factors for host determination of influenza A viruses. However, much less is known about the factors driving IBV replication in humans. We hypothesize that similar factors influence the host restriction of IBV. Here, we compile and review the current understanding of host factors crucial for the various stages of the IBV viral replication cycle. While …

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Cocaine Use Disorder Effects On Blood Oxytocin Levels And Oxtr Dna Methylation, Manassés Soares Souza, Breno Sanvicente-Vieira, Aline Zaparte, Talita Baptista, Maria Aparecida Nagai, Flávia Rotea Mangone, Ana Carolina Pavanelli, Thiago Wendt Viola, Rodrigo Grassi-Oliveira Sep 2023

Cocaine Use Disorder Effects On Blood Oxytocin Levels And Oxtr Dna Methylation, Manassés Soares Souza, Breno Sanvicente-Vieira, Aline Zaparte, Talita Baptista, Maria Aparecida Nagai, Flávia Rotea Mangone, Ana Carolina Pavanelli, Thiago Wendt Viola, Rodrigo Grassi-Oliveira

School of Medicine Faculty Publications

Substance use disorders have been associated with alterations in the oxytocinergic system, but few studies have investigated both the peptide and epigenetic mechanisms potentially implicated in the regulation of oxytocin receptor. In this study, we compared plasma oxytocin and blood DNA methylation in the OXTR gene between people with and without cocaine use disorder (CUD). We measured the oxytocin levels of 51 people with CUD during acute abstinence and of 30 healthy controls using an enzyme immunoassay. The levels of DNA methylation in four CpG sites at exon III of the OXTR gene were evaluated in a subsample using pyrosequencing. …

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Methionine Biosynthesis Enzyme Momet2 Is Required For Rice Blast Fungus Pathogenicity By Promoting Virulence Gene Expression Via Reducing 5mc Modification, Huimin Li, Pengcheng Mo, Jun Zhang, Zhuoer Xie, Xinyu Liu, Han Chen, Leiyun Yang, Muxing Liu, Haifeng Zhang, Ping Wang, Zhengguang Zhang Sep 2023

Methionine Biosynthesis Enzyme Momet2 Is Required For Rice Blast Fungus Pathogenicity By Promoting Virulence Gene Expression Via Reducing 5mc Modification, Huimin Li, Pengcheng Mo, Jun Zhang, Zhuoer Xie, Xinyu Liu, Han Chen, Leiyun Yang, Muxing Liu, Haifeng Zhang, Ping Wang, Zhengguang Zhang

School of Medicine Faculty Publications

The emergence of fungicide resistance severely threatens crop production by limiting the availability and application of established fungicides. Therefore, it is urgent to identify new fungicidal targets for controlling plant diseases. Here, we characterized the function of a conserved homoserine O-acetyltransferase (HOA) from the rice blast fungus Magnaporthe oryzae that could serve as the candidate antifungal target. Deletion of the MoMET2 and MoCYS2 genes encoding HOAs perturbed the biosynthesis of methionine and S-adenyl methionine, a methyl group donor for epigenetic modifications, and severely attenuated the development and virulence of M. oryzae. The ΔMomet2 mutant is significantly increased in 5-methylcytosine (5mC) …

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Her3 Functions As An Effective Therapeutic Target In Triple Negative Breast Cancer To Potentiate The Antitumor Activity Of Gefitinib And Paclitaxel, Hui Lyu, Fei Shen, Sanbao Ruan, Congcong Tan, Jundong Zhou, Ann D. Thor, Bolin Liu Sep 2023

Her3 Functions As An Effective Therapeutic Target In Triple Negative Breast Cancer To Potentiate The Antitumor Activity Of Gefitinib And Paclitaxel, Hui Lyu, Fei Shen, Sanbao Ruan, Congcong Tan, Jundong Zhou, Ann D. Thor, Bolin Liu

School of Medicine Faculty Publications

Background: Triple negative breast cancer (TNBC) represents a significant clinical challenge. Chemotherapy remains the mainstay for a large part of TNBC patients, whereas drug resistance and tumor recurrence frequently occur. It is in urgent need to identify novel molecular targets for TNBC and develop effective therapy against the aggressive disease. Methods: Immunohistochemistry was performed to examine the expression of HER3 in TNBC samples. Western blots were used to assess protein expression and activation. Cell proliferation and viability were determined by cell growth (MTS) assays. TCGA databases were analyzed to correlate HER3 mRNA expression with the clinical outcomes of TNBC patients. …

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Isolated Cerebral Mucormycosis And Aspergillosis Coinfection In An Immunocompromised Adult, George Sun, Allison Weiss, Joy Zhao, Mitchell Silver, Michael Demaio, Sara Dehbashi Aug 2023

Isolated Cerebral Mucormycosis And Aspergillosis Coinfection In An Immunocompromised Adult, George Sun, Allison Weiss, Joy Zhao, Mitchell Silver, Michael Demaio, Sara Dehbashi

Department of Neurology Faculty Papers

Opportunistic fungal infections are a major cause of mortality in immunosuppressed patients, with mucormycosis and aspergillosis as two of the most commonly identified fungal organisms. Coinfection with mucormycosis and aspergillosis is rare, but cases have been reported in literature, most commonly presenting as disseminated invasive fungal infection with cerebrorhino-orbital involvement in an immunocompromised patient. Infections are most commonly caused by direct implantation of spores with localised angioinvasion. Haematogenous spread is rare, with most cases secondary to haematological malignancies or intravenous drug use. Coinfection with mucormycosis and aspergillosis portends a poor prognosis, with a high mortality rate. Thus, prompt recognition and …

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The Gpcr-Gαs-Pka Signaling Axis Promotes T Cell Dysfunction And Cancer Immunotherapy Failure, Victoria H Wu, Bryan S Yung, Farhoud Faraji, Robert Saddawi-Konefka, Zhiyong Wang, Alexander T Wenzel, Miranda J Song, Meghana S Pagadala, Lauren M Clubb, Joshua Chiou, Sanju Sinha, Marin Matic, Francesco Raimondi, Thomas S Hoang, Rebecca Berdeaux, Dario A A Vignali, Ramiro Iglesias-Bartolome, Hannah Carter, Eytan Ruppin, Jill P Mesirov, J Silvio Gutkind Aug 2023

The Gpcr-Gαs-Pka Signaling Axis Promotes T Cell Dysfunction And Cancer Immunotherapy Failure, Victoria H Wu, Bryan S Yung, Farhoud Faraji, Robert Saddawi-Konefka, Zhiyong Wang, Alexander T Wenzel, Miranda J Song, Meghana S Pagadala, Lauren M Clubb, Joshua Chiou, Sanju Sinha, Marin Matic, Francesco Raimondi, Thomas S Hoang, Rebecca Berdeaux, Dario A A Vignali, Ramiro Iglesias-Bartolome, Hannah Carter, Eytan Ruppin, Jill P Mesirov, J Silvio Gutkind

Journal Articles

Immune checkpoint blockade (ICB) targeting PD-1 and CTLA-4 has revolutionized cancer treatment. However, many cancers do not respond to ICB, prompting the search for additional strategies to achieve durable responses. G-protein-coupled receptors (GPCRs) are the most intensively studied drug targets but are underexplored in immuno-oncology. Here, we cross-integrated large singe-cell RNA-sequencing datasets from CD8+ T cells covering 19 distinct cancer types and identified an enrichment of Gαs-coupled GPCRs on exhausted CD8+ T cells. These include EP2, EP4, A2AR, β1AR and β2AR, all of which promote T cell dysfunction. We also developed transgenic mice expressing a chemogenetic CD8-restricted Gαs–DREADD to activate …

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Investigating The Physiological Mechanisms Between Resistance Training And Pain Relief In The Cancer Population: A Literature Review, Yvonne Jiang, Peter C. Angeletti, Amy J. Hoffman Jul 2023

Investigating The Physiological Mechanisms Between Resistance Training And Pain Relief In The Cancer Population: A Literature Review, Yvonne Jiang, Peter C. Angeletti, Amy J. Hoffman

Nebraska Center for Virology: Faculty Publications

This literature review examines the mechanisms of how exercise, specifically in the form of resistance training, may lead to pain relief in the cancer population. Primary data from three different cancer populations: breast, prostate, and lung, will be examined. A number of experimental studies have been conducted to confirm the effectiveness of resistance training on pain relief as well as the biochemical pathways that relate to this process. In this review, we will examine 5 randomized controlled trials. For the purposes of this review, pain is defined as physical suffering or discomfort associated with illness. Pain is the body’s natural …

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Editorial: Targeting Dna Damage Response To Enhance Antitumor Innate Immunity In Radiotherapy, Victoria Valvo, Emanuele Vitale, Marco Tigano, Rachel Evans, Meredith A. Morgan, Qiang Zhang Jul 2023

Editorial: Targeting Dna Damage Response To Enhance Antitumor Innate Immunity In Radiotherapy, Victoria Valvo, Emanuele Vitale, Marco Tigano, Rachel Evans, Meredith A. Morgan, Qiang Zhang

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

No abstract provided.

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Sars‑Cov‑2 Entry Into And Evolution Within A Skilled Nursing Facility, Nicole R. Sexton, Parker Parker Cline, Emily N. Gallichotte, Emily Fitzmeyer, Michael C. Young, Ashley J. Janich, Kristy L. Pabilonia, Nicole Ehrhart, Gregory D. Ebel Jul 2023

Sars‑Cov‑2 Entry Into And Evolution Within A Skilled Nursing Facility, Nicole R. Sexton, Parker Parker Cline, Emily N. Gallichotte, Emily Fitzmeyer, Michael C. Young, Ashley J. Janich, Kristy L. Pabilonia, Nicole Ehrhart, Gregory D. Ebel

Nebraska Center for Virology: Faculty Publications

SARS-CoV-2 belongs to the family Coronaviridae which includes multiple human pathogens that have an outsized impact on aging populations. As a novel human pathogen, SARS-CoV-2 is undergoing continuous adaptation to this new host species and there is evidence of this throughout the scientific and public literature. However, most investigations of SARS-CoV-2 evolution have focused on largescale collections of data across diverse populations and/or living environments. Here we investigate SARS-CoV-2 evolution in epidemiologically linked individuals within a single outbreak at a skilled nursing facility beginning with initial introduction of the pathogen. The data demonstrate that SARSCoV- 2 was introduced to the …

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Structural Insights Into Rna Bridging Between Hiv-1 Vif And Antiviral Factor Apobec3g, Takahide Kouno, Satoshi Shibata, Megumi Shigematsu, Jaekyung Hyun, Tae Gyun Kim, Hiroshi Matsuo, Matthias Wolf Jul 2023

Structural Insights Into Rna Bridging Between Hiv-1 Vif And Antiviral Factor Apobec3g, Takahide Kouno, Satoshi Shibata, Megumi Shigematsu, Jaekyung Hyun, Tae Gyun Kim, Hiroshi Matsuo, Matthias Wolf

Computational Medicine Center Faculty Papers

Great effort has been devoted to discovering the basis of A3G-Vif interaction, the key event of HIV's counteraction mechanism to evade antiviral innate immune response. Here we show reconstitution of the A3G-Vif complex and subsequent A3G ubiquitination in vitro and report the cryo-EM structure of the A3G-Vif complex at 2.8 Å resolution using solubility-enhanced variants of A3G and Vif. We present an atomic model of the A3G-Vif interface, which assembles via known amino acid determinants. This assembly is not achieved by protein-protein interaction alone, but also involves RNA. The cryo-EM structure and in vitro ubiquitination assays identify an adenine/guanine base …

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Adjuvanted Fusion Protein Vaccine Induces Durable Immunity To Onchocerca Volvulus In Mice And Non-Human Primates, Nathan M. Ryan, Jessica A. Hess, Erica J. Robertson, Nancy Tricoche, Cheri Turner, Jenn Davis, Nikolai Petrovsky, Melissa Ferguson, William J. Rinaldi, Valerie M. Wong, Ayako Shimada, Bin Zhan, Maria Elena Bottazzi, Benjamin L. Makepece, Sean A. Gray, Darrick Carter, Sara Lustigman, David Abraham Jul 2023

Adjuvanted Fusion Protein Vaccine Induces Durable Immunity To Onchocerca Volvulus In Mice And Non-Human Primates, Nathan M. Ryan, Jessica A. Hess, Erica J. Robertson, Nancy Tricoche, Cheri Turner, Jenn Davis, Nikolai Petrovsky, Melissa Ferguson, William J. Rinaldi, Valerie M. Wong, Ayako Shimada, Bin Zhan, Maria Elena Bottazzi, Benjamin L. Makepece, Sean A. Gray, Darrick Carter, Sara Lustigman, David Abraham

Department of Microbiology and Immunology Faculty Papers

Onchocerciasis remains a debilitating neglected tropical disease. Due to the many challenges of current control methods, an effective vaccine against the causative agent Onchocerca volvulus is urgently needed. Mice and cynomolgus macaque non-human primates (NHPs) were immunized with a vaccine consisting of a fusion of two O. volvulus protein antigens, Ov-103 and Ov-RAL-2 (Ov-FUS-1), and three different adjuvants: Advax-CpG, alum, and AlT4. All vaccine formulations induced high antigen-specific IgG titers in both mice and NHPs. Challenging mice with O. volvulus L3 contained within subcutaneous diffusion chambers demonstrated that Ov-FUS-1/Advax-CpG-immunized animals developed protective immunity, durable for at least 11 weeks. Passive …

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Yes-Associated Protein-1 Overexpression In Ocular Surface Squamous Neoplasia; A Potential Diagnostic Marker And Therapeutic Target, Peter Julius, Stepfanie N. Siyumbwa, Fred Maate, Phyllis Moonga, Guobin Kang, Trevor Kaile, John T. T., Charles Wood Jul 2023

Yes-Associated Protein-1 Overexpression In Ocular Surface Squamous Neoplasia; A Potential Diagnostic Marker And Therapeutic Target, Peter Julius, Stepfanie N. Siyumbwa, Fred Maate, Phyllis Moonga, Guobin Kang, Trevor Kaile, John T. T., Charles Wood

Nebraska Center for Virology: Faculty Publications

Yes-associated protein-1 (YAP-1) is a Hippo system transcription factor, which serves as an oncogene in squamous cell carcinoma, and several solid tumors when the Hippo pathway is dysregulated. Yet, the activity of YAP-1 in ocular surface squamous neoplasia (OSSN) has not been determined. Here, we investigate the relationship between YAP-1 overexpression and OSSN. Using a cross-sectional study design, we recruited 227 OSSN patients from the University Teaching Hospitals in Lusaka, Zambia. Immunohistochemistry was used to assess YAP-1 protein overexpression in tumor tissue relative to surrounding benign squamous epithelium. OSSN patient samples (preinvasive, n = 62, 27% and invasive, n = …

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