Microbiology Commons^™

Domain I Of The 5′ Non-Translated Genomic Region In Coxsackievirus B3 Rna Is Not Required For Productive Replication, L. Jaramillo, S. Smithee, S. Tracy, N. M. Chapman

Nebraska Center for Virology: Faculty Publications

Domain I is a cloverleaf-like secondary structure at the 5′ termini of all enterovirus genomes, comprising part of a cis-acting replication element essential for efficient enteroviral replication. 5′ genomic terminal deletions up to as much as 55% of domain I can occur without lethality following coxsackie B virus infections. We report here that the entire CVB structural domain I can be deleted without lethality.

Reversion To Wildtype Of A Mutated And Nonfunctional Coxsackievirus B3cre(2c), Shane Smithee, Steven Tracy, Nora M. Chapman

Nebraska Center for Virology: Faculty Publications

The cis-acting replication element (CRE) in the 2C protein coding region [CRE(2C)] of enteroviruses (EV) facilitates the addition of two uridine residues (uridylylation) onto the virus-encoded protein VPg inorder for it to serve as the RNA replication primer. We demonstrated that coxsackievirus B3 (CVB3) is replication competent in the absence of a native (uridylylating) CRE(2C) and also demonstrated that lackof a functional CRE(2C) led to generation of 5’ terminal genomic deletions in the CVB3 CRE-knock-out (CVB3-CKO) population. We asked whether reversion of the mutated CRE(2C) occurred, thus permitting sustained replication, and when were 5’ terminal deletions generated during replication. Virions …

Replicating Single-Cycle Adenovirus Vectors Generate Amplified Influenza Vaccine Responses, Catherine M. Crosby, William E. Matchett, Stephanie S. Anguiano-Zarate, Christopher A. Parks, Eric A. Weaver, Larry R. Pease, Richard J. Webby, Michael A. Barry

Nebraska Center for Virology: Faculty Publications

Head-to-head comparisons of conventional influenza vaccines with ade- novirus (Ad) gene-based vaccines demonstrated that these viral vectors can mediate more potent protection against influenza virus infection in animal models. In most cases, Ad vaccines are engineered to be replication-defective (RD-Ad) vectors. In contrast, replication-competent Ad (RC-Ad) vaccines are markedly more potent but risk causing adenovirus diseases in vaccine recipients and health care workers. To harness antigen gene replication but avoid production of infectious virions, we de- veloped “single-cycle” adenovirus (SC-Ad) vectors. Previous work demonstrated that SC-Ads amplify transgene expression 100-fold and produce markedly stronger and more persistent immune responses than …

Effect Of Two-Year Caloric Restriction On Bone Metabolism And Bone Mineral Density In Non-Obese Younger Adults: A Randomized Clinical Trial, Dt Villareal, L Fontana, Sk Das, Et Al.

Faculty, Staff and Students Publications

Although caloric restriction (CR) could delay biologic aging in humans, it is unclear if this would occur at the cost of significant bone loss. We evaluated the effect of prolonged CR on bone metabolism and bone mineral density (BMD) in healthy younger adults. Two-hundred eighteen non-obese (body mass index [BMI] 25.1?±?1.7?kg/m(2) ), younger (age 37.9?±?7.2 years) adults were randomly assigned to 25% CR (CR group, n?=?143) or ad libitum (AL group, n?=?75) for 2 years. Main outcomes were BMD and markers of bone turnover. Other outcomes included body composition, bone-active hormones, nutrient intake, and physical activity. Body weight (-7.5?±?0.4 versus …

Local Corticotropin Releasing Hormone (Crh) Signals To Its Receptor Crhr1 During Postnatal Development Of The Mouse Olfactory Bulb, Isabella Garcia, Paramjit K Bhullar, Burak Tepe, Joshua Ortiz-Guzman, Longwen Huang, Alexander M Herman, Lesley Chaboub, Benjamin Deneen, Nicholas J Justice, Benjamin R Arenkiel

Faculty, Staff and Students Publications

Neuropeptides play important physiological functions during distinct behaviors such as arousal, learning, memory, and reproduction. However, the role of local, extrahypothalamic neuropeptide signaling in shaping synapse formation and neuronal plasticity in the brain is not well understood. Here, we characterize the spatiotemporal expression profile of the neuropeptide corticotropin-releasing hormone (CRH) and its receptor CRHR1 in the mouse OB throughout development. We found that CRH-expressing interneurons are present in the external plexiform layer, that its cognate receptor is expressed by granule cells, and show that both CRH and CRHR1 expression enriches in the postnatal period when olfaction becomes important towards olfactory-related …

Inhibition Of Bacterial Growth And Prevention Of Bacterial Adhesion With Localized Nitric Oxide Delivery, Julia Osborne

Dissertations, Master's Theses and Master's Reports

Bacterial infections continue to be a problem at the site of an indwelling medical device, and over the years, various bacterial strains have become more resistant to current antibiotic treatments. Bacterial infection at an indwelling medical device can be dangerous and affect the performance of the medical device which can ultimately lead to the failure of the device due to bacterial resistance to treatment.

Nitric Oxide (NO) has been shown to possess antibacterial properties to prevent and inhibit bacterial growth. NO releasing coatings on indwelling medical devices could provide a reduction in bacterial infections that occur at the device site …

The Impact Of Urbanization On Mosquito-Borne Viruses, Nikhita Puthuveetil

Undergraduate Research Posters

Mosquito-borne diseases such as yellow fever, dengue, and West Nile are rapidly emerging across the globe. Their emergence is often aided by the growth of their vector population, or the organisms that transmit the virus to the host. Urbanization and land use often destroys the habitat of the virus and its vector. However, the virus and its vector often survive despite the changes to its environment. The goal of this paper is to find out exactly how urbanization and changes in land use affect mosquito-borne viruses and how these viruses survive despite the destruction of their habitats. To understand how …

Phylogenetic Investigation Of Enteric Bovine Coronavirus In Ireland Reveals Partitioning Between European And Global Strains, Lynda Gunn, P. J. Collins, M. J. O'Connell, Helen O'Shea

Department of Biological Sciences Publications

Background

Bovine coronavirus is a primary cause of neonatal calf diarrhea worldwide, and is also associated with acute diarrhea in adult cattle during the winter season. There are no reports on molecular characterization of bovine coronavirus in Ireland, and little data exists apart from serological studies.

Findings

In this study, 11 neonatal (mean age 9 days) calf BCoV strains from the south of Ireland were collected over a one year period and characterized using molecular methods. The spike gene which encodes a protein involved in viral entry, infectivity and immune response shows the most variability amongst the isolates and was …

Fungal Melanin: What Do We Know About Structure?, Joshua D. Nosanchuk, Ruth E. Stark, Arturo Casadevall

Publications and Research

The production of melanin significantly enhances the virulence of many important human pathogenic fungi. Despite fungal melanin’s importance in human disease, as well as melanin’s contribution to the ability of fungi to survive in diverse hostile environments, the structure of melanin remains unsolved. Nevertheless, ongoing research efforts have progressively revealed several notable structural characteristics of this enigmatic pigment, which will be the focus of this review. These compositional and organizational insights could further our ability to develop novel therapeutic approaches to combat fungal disease and enhance our understanding of how melanin is inserted into the cell wall.

Design And Testing Of Novel Anthrax Vaccines Utilizing A Tobacco Mosaic Virus Expression System, Ryan C. Mccomb

KGI Theses and Dissertations

Anthrax is a potentially fatal disease caused by the bacteria Bacillus anthracis. Infection and disease occur after spores gain entry into the body, germinate into vegetative bacteria, and produce toxin. Bacillus anthracis spores have been engineered as bioweapons and have been used repeatedly in warfare and terrorism to inflict casualties in military and civilian populations. Currently, only one vaccine has been approved for prevention of anthrax in the United States. This vaccine is an undefined product that is difficult to produce, requires a long vaccination schedule, and is reactogenic. Efforts to make an improved anthrax vaccine are being pursued. …

Effect Of Raised Body Fat On Vitamin D, Leptin And Bone Mass, Syeda Sadia Fatima, Saad Farooq, Maaida Asif Tauni, Omar Irfan, Faiza Alam

Department of Biological & Biomedical Sciences

Objective: To estimate leptin, vitamin D and bone mineral density levels in individuals with high fat mass, and to assess any correlation.Methods: The cross-sectional study was conducted at the Basic Medical Sciences Institute, Jinnah Post Graduate Medical Centre, Karachi, and Aga Khan University, Karachi, from August 2012 to July 2014, and comprised healthy male volunteers between the ages of 18-60 years. Body fat percentage was determined using bioelectrical impedance analysis and the participants were classified as: Group A (15-21.9); Group B (22-27.9); and Group C ( > 28). Bone mineral density was calculated by ultrasound bone densitometer (T-score between +1 and …

Donor Platelet Plasma Components Inactivate Sensitive And Multidrug Resistant Acinetobacter Baumannii Isolates, Chelsea M. Edelblute, Olga N. Pakhomova, Fanying Li, Barbara Y. Hargrave, Loree C. Heller

Bioelectrics Publications

Acinetobacter baumannii is an environmentally resilient healthcare-associated opportunistic pathogen responsible for infections at many body sites. In the last 10 years, clinical strains resistant to many or all commonly used antibiotics have emerged globally. With few antimicrobial agents in the pharmaceutical pipeline, new and alternative agents are essential. Platelets secrete a large number of proteins, including proteins with antimicrobial activity. In a previous study, we demonstrated that donor platelet supernatants and plasma significantly inhibited the growth of a reference strain of A. baumannii in broth and on skin. This inhibition appeared to be unrelated to the platelet activation state. In …

Expansion Of The Chlorovirus Genus By Studies On Virus Natural History And Chlorella Host Metabolism, Cristian F. Quispe

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

Inland waters cover about 2.5 percent of our planet and harbor huge numbers of known and unknown microorganisms including viruses. Viruses likely play dynamic, albeit largely undocumented roles in regulating microbial communities and in recycling nutrients in the ecosystem. Phycodnaviruses are a genetically diverse, yet morphologically similar, group of large dsDNA-containing viruses (160- to 560-kb) that inhabit aquatic environments. Members of the genus Chlorovirus are common in freshwater. They replicate in eukaryotic, single-celled, chlorella-like green algae that normally exist as endosymbionts of protists in nature. Very little is known about the natural history of the chloroviruses and how they achieve …

Reduction Of Campylobacter Jejuni On Chicken Wingettes By Treatment With Caprylic Acid, Chitosan Or Protective Cultures Of Lactobacillus Spp., Ann Nicole Woo-Ming

Graduate Theses and Dissertations

Poultry is one of the main sources of protein in the United States and in 2014 Americans ate approximately 100 lbs per person. However, consumption of poultry products is strongly associated with foodborne illness from Campylobacter. In the first study, chitosan, caprylic acid and their combination were evaluated as a coating treatment for the reduction of Campylobacter jejuni on poultry products. For the initial screening trials, chitosan of three different molecular weights (15-50 kDa, 190-310 kDa and 400-600 kDa) was evaluated at three concentrations (0.5%, 1.0%, 2.0%) and separately, caprylic acid was tested at 0.5%, 1.0% and 2.0% using chicken …

Detection Methods And Intestinal Adherence Of Non-O157 Shiga Toxin-Producing Escherichia Coli, Zachary R. Stromberg

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

Shiga toxin-producing Escherichia coli (STEC) are enteric pathogens of humans. Cattle serve as a reservoir and harbor STEC in their intestines. Intimin-positive STEC are referred to as enterohemorrhagic E.coli (EHEC). Seven serogroups (O26, O45, O103, O111, O121, O145, and O157) account for the majority of illness due to STEC and are hereafter referred to as STEC/EHEC-7. To improve detection, enrichment broths were compared for supporting growth of STEC-7 and STEC O104:H4 (STEC-8). In pure culture, STEC enriched in trypticase soy broth (TSB) had significantly greater growth compared to TSB containing antimicrobials. In fecal samples, E. coli broth enrichment yielded …

Spectrum Of Histopathological Findings In Postmenopausal Bleeding, Muhammad Usman Tariq, Romana Idress, Ahmed Raheem, Naila Kayani

Department of Pathology and Laboratory Medicine

Objective:To determine the frequencies of histopathological findings in endometrial and endocervical biopsy samples with clinical history of Postmenopausal Bleeding (PMB). Study Design:Descriptive cross-sectional study. Place and Duration of Study:Section of Histopathology, Department of Pathology and Laboratory Medicine, The Aga Khan University Hospital, Karachi, from February 2012 to January 2013. Methodology:Atotal of 157 consecutive endometrial and endocervical biopsy specimens with history of postmenopausal bleeding were included. After microscopic examination, frequencies of histological findings in different age groups were generated. Chi-square and independent sample t-tests were applied to see whether the difference was significant which was set at p < 0.05. Results:One hundred and twenty-one (77.1%) specimens showed benign pathologies while 36 (22.9%) were malignant. Endometrial polyp was seen in 67 (42.7%) cases followed by endometrial carcinomas in 25 (15.9%), endometrial hyperplasia in 21 (13.4%), cervical carcinoma in 12 (7.6%) and cervical polyps in 9 (5.7%) cases. Ahighly significant increase in the percentage of malignant and pre-malignant lesions was seen with increasing age group (p < 0.001). Mean age of patients with type-2 endometrial carcinoma was higher than type-1 endometrial carcinoma but statistical significance was not observed (70.2 ±6.5 vs. 61.8 ±9.1 years respectively, p=0.069). Conclusion:Although benign pathologies were more common in postmenopausal bleeding but the collective proportion of endometrial and cervical malignancies and pre-malignant conditions was quite high. Therefore, PMB should be urgently evaluated for cause and early commencement of treatment

Cyclic Di-Gmp-Mediated Repression Of Swarming Motility By Pseudomonas Aeruginosa Pa14 Requires The Motab Stator, S. L. Kuchma, N. J. Delalez, L. M. Filkins, E. A. Snavely, J. P. Armitage, G. A. O'Toole

Dartmouth Scholarship

The second messenger cyclic diguanylate (c-di-GMP) plays a critical role in the regulation of motility. In Pseudomonas aeruginosa PA14, c-di-GMP inversely controls biofilm formation and surface swarming motility, with high levels of this dinucleotide signal stimulating biofilm formation and repressing swarming. P. aeruginosa encodes two stator complexes, MotAB and MotCD, that participate in the function of its single polar flagellum. Here we show that the repression of swarming motility requires a functional MotAB stator complex. Mutating the motAB genes restores swarming motility to a strain with artificially elevated levels of c-di-GMP as well as stimulates swarming in the wild-type strain, …

Steroid Receptor Isoform Expression In Drosophila Nociceptor Neurons Is Required For Normal Dendritic Arbor And Sensitivity, Aidan L. Mcparland, Taylor L. Follansbee, Gwendolyn D. Vesenka, Alexandra E. Panaitiu, Geoffrey K. Ganter

Biology Student Publications

Steroid hormones organize many aspects of development, including that of the nervous system. Steroids also play neuromodulatory and other activational roles, including regulation of sensitivity to painful stimuli in mammals. In Drosophila, ecdysteroids are the only steroid hormones, and therefore the fly represents a simplified model system in which to explore mechanisms of steroid neuromodulation of nociception. In this report, we present evidence that ecdysteroids, acting through two isoforms of their nuclear ecdysone receptor (EcR), modulate sensitivity to noxious thermal and mechanical stimuli in the fly larva. We show that EcRA and EcRB1 are expressed by third instar larvae in …

Loss Of Glycosaminoglycan Receptor Binding After Mosquito Cell Passage Reduces Chikungunya Virus Infectivity, Amber M. Paul, Dhiraj Acharya, John F. Anderson, Faqing Huang, Fengwei Bai

Publications

Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that can cause fever and chronic arthritis in humans. CHIKV that is generated in mosquito or mammalian cells differs in glycosylation patterns of viral proteins, which may affect its replication and virulence. Herein, we compare replication, pathogenicity, and receptor binding of CHIKV generated in Vero cells (mammal) or C6/36 cells (mosquito) through a single passage. We demonstrate that mosquito cell derived CHIKV (CHIKVmos) has slower replication than mammalian cell derived CHIKV (CHIKVvero), when tested in both human and murine cell lines. Consistent with this, CHIKVmos infection in both cell lines produce less cytopathic …

A Tail Of Two Phages: Genomic And Functional Analysis Of Listeria Monocytogenes Phages Vb_Lmos_188 And Vb_Lmos_293 Reveal The Receptor-Binding Proteins Involved In Host Specificity, Aidan Casey, Kieran Jordan, Horst Neve, Aidan Coffey, Olivia Mcauliffe

Department of Biological Sciences Publications

The physical characteristics of bacteriophages establish them as viable candidates for downstream development of pathogen detection assays and biocontrol measures. To utilize phages for such purposes, a detailed knowledge of their host interaction mechanisms is a prerequisite. There is currently a wealth of knowledge available concerning Gram-negative phage-host interaction, but little by comparison for Gram-positive phages and Listeria phages in particular. In this research, the lytic spectrum of two recently isolated Listeria monocytogenes phages (vB_LmoS_188 and vB_LmoS_293) was determined, and the genomic basis for their observed serotype 4b/4e host-specificity was investigated using comparative genomics. The late tail genes of these …

Variation In Microbiome Composition And Stability For A Vancomycin Treated Primary Sclerosing Cholangitis Patient With Ulcerative Colitis Compared With Controls, Alanna Dubrovsky

Symposium

The bacterial composition of the human intestines contributes to much more than just digestion. In the inflammatory, autoimmune conditions primary sclerosing cholangitis (PSC) and ulcerative colitis (UC), the microbiome may be, in some cases, a factor. To gain a better understanding of the composition and stability of the microbiome in a patient treated with vancomycin for PSC, terminal restriction fragment (TRF) analysis was performed on 13 controls and 1 patient, and 16s rRNA microbiome composition analysis was performed on 1 patient and 3 controls. Results showed similar levels of stability, with surprising differences in composition.

Establishing Quality Control Values For Hematology Parameters: An Insight, Muhammad Shariq Shaikh

Department of Pathology and Laboratory Medicine

No abstract provided.

Lymphangioma Circumscriptum: Clinicopathological Spectrum Of 29 Cases, Saira Fatima, Nasir Uddin, Romana Idrees, Khurram Minhas, Zubair Ahmad, Rashida Ahmad, Naila Kayani, Muhammad Arif

Department of Pathology and Laboratory Medicine

Objective:
To describe the clinicopathological spectrum of Lymphangioma Circumscriptum (LC).
Study Design:
Observational case series.
Place and Duration of Study:
Department of Pathology and Microbiology, AKUH, Karachi, from 2002 to 2012.
Methodology:
All reported cases of LC were retrieved from medical record. Clinical and pathological features were noted. Frequency percentages were determined.
Results:
There were 29 cases of LC predominantly males (62%). The mean age was 27.17 ±15.5 years. The commonest sites was anal/perianal region (24%) followed by extremities (17%) and tongue, (14%). Vulval LC was seen in 3 patients. Two cases were described on scrotum. The lesions were most …

Pathogen-Specific Burdens Of Community Diarrhoea In Developing Countries: A Multisite Birth Cohort Study (Mal-Ed), Sadia Shakoor, Shahida Qureshi, Furqan Kabir, Anita K. M. Zaidi, Zulfiqar Ahmed Bhutta, Imran Ahmed, Didar Alam, Syed Asad Ali, Muneera Rasheed, Sajid Bashir Soofi, Ali Turab, Aisha Khizar Yousafzai

Department of Pathology and Laboratory Medicine

Background: Most studies of the causes of diarrhoea in low-income and middle-income countries have looked at severe disease in people presenting for care, and there are few estimates of pathogen-specific diarrhoea burdens in the community.
Methods: We undertook a birth cohort study with not only intensive community surveillance for diarrhoea but also routine collection of non-diarrhoeal stools from eight sites in South America, Africa, and Asia. We enrolled children within 17 days of birth, and diarrhoeal episodes (defined as maternal report of three or more loose stools in 24 h, or one loose stool with visible blood) were identified through …

Role Of The Dna Sensor Sting In Protection From Lethal Infection Following Corneal And Intracerebral Challenge With Herpes Simplex Virus 1, Zachary M. Parker, Aisling A. Murphy, David. A. Leib

Dartmouth Scholarship

STING is a protein in the cytosolic DNA and cyclic dinucleotide sensor pathway that is critical for the initiation of innate responses to infection by various pathogens. Consistent with this, herpes simplex virus 1 (HSV-1) causes invariable and rapid lethality in STING-deficient (STING(-/-)) mice following intravenous (i.v.) infection. In this study, using real-time bioluminescence imaging and virological assays, as expected, we demonstrated that STING(-/-) mice support greater replication and spread in ocular tissues and the nervous system. In contrast, they did not succumb to challenge via the corneal route even with high titers of a virus that was routinely lethal …

Prevalence Of A Chytrid Pathogen (Batrachochytrium Dendrobatidis) In Eastern Hellbender Salamanders In New York And Pennsylvania, Linxuan Wu

Biology Theses

Amphibian populations are currently declining globally. There are many possible causes for these declines, among which an emerging infectious disease, chytridiomycosis, has been implicated. Chytridiomycosis in the U.S.A. is mainly caused by the Batrachochytrium dendrobatidis. In this study, I used qPCR assays to detect the existence of this pathogen in the Eastern Hellbender (Cryptobranchus alleganiensis alleganiensis) populations in the Allegheny and Susquehanna River drainages of New York and Pennsylvania. Chytrid is most often tested by using skin swabs, but in this study, tail clips, dorsal skin, blood and eggs were tested as well. Batrachochytrium dendrobatidis was detected …

Autologous Hematopoietic Stem Cell Transplantation-10 Years Of Data From A Developing Country, Natasha Ali, Salman Naseem Adil, Mohammad Usman Shaikh

Department of Pathology and Laboratory Medicine

Intensive chemotherapy followed by autologous stem cell transplantation is the treatment of choice for patients with hematological malignancies. The objective of the present study was to evaluate the outcomes of patients with mainly lymphoma and multiple myeloma after autologous stem cell transplant. The pretransplant workup consisted of the complete blood count, an evaluation of the liver, kidney, lung, and infectious profile, chest radiographs, and a dental review. For lymphoma, all patients who achieved at least a 25% reduction in the disease after salvage therapy were included in the study. Mobilization was done with cyclophosphamide, followed by granulocyte colony-stimulating factor, 300 …

Kaposi’S Sarcoma-Associated Herpesvirus Transmission And Infection Among Young Zambian Children, Landon N. Olp

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

Kaposi’s sarcoma-associated herpesvirus (KSHV) is the etiologic agent for all forms of Kaposi’s sarcoma (KS)—one of the most common pediatric cancers in sub-Saharan Africa during the AIDS epidemic. KS was endemic in sub-Saharan Africa prior to the HIV/AIDS epidemic, but KS cases drastically increased thereafter. Our laboratory previously observed that KSHV infection is common among Zambian children and saliva is the major route of transmission. However, additional factors associated with the transmission of KSHV to children are poorly understood. Since a vaccine against KSHV is not currently available, it is paramount to understand factors associated with transmission so that alternative …

Symptomatic Surgically Treated Non-Neoplastic Cysts Of The Central Nervous System: A Clinicopathological Study From Pakistan, Nasir Ud Din, Huma Arshad, Zubair Ahmad, Sheema H Hasan, Mohammad Ehsan Bar

Department of Pathology and Laboratory Medicine

Objective: To report clinicopathologic features of symptomatic surgically removed non-neoplastic cysts of the central nervous system (CNS). Study Design: Case series. Place and Duration of Study: The Aga Khan University Hospital, Karachi, from 2003 to 2012. Methodology: All non-neoplastic CNS cysts reported during the study period were retrieved and reviewed. Age, gender, location, histologic type and clinical features were noted. Results: A total of 124 cysts were diagnosed in the study period. These included 44 epidermoid cysts (mean age 30.5 ± 13.8 years), 35 colloid cysts (mean age 31 ± 13.2 years), 32 arachnoid cysts (mean age 24.8 ± 20.2 …

Selective Involvement Of The Checkpoint Regulator Vista In Suppression Of B-Cell, But Not T-Cell, Responsiveness By Monocytic Myeloid-Derived Suppressor Cells From Mice Infected With An Immunodeficiency-Causing Retrovirus, Kathy A. Green, Li Wang, Randolph J. Noelle, William R. Green

Dartmouth Scholarship

Inhibition of T-cell responses in tumor microenvironments by myeloid-derived suppressor cells (MDSCs) is widely accepted. We demonstrated augmentation of monocytic MDSCs whose suppression of not only T-cell, but also B-cell, responsiveness paralleled the immunodeficiency during LP-BM5 retrovirus infection. MDSCs inhibited T cells by inducible nitric oxide synthase (iNOS)/nitric oxide (NO), but uniquely, inhibition of B cells was ~50% dependent each on iNOS/NO and the MDSC-expressed negative-checkpoint regulator VISTA. Blockade with a combination of iNOS/NO and VISTA caused additive or synergistic abrogation of MDSC-mediated suppression of B-cell responsiveness.