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Articles 121 - 150 of 161
Full-Text Articles in Microbiology
Role Of Mhc Antigens And Immunoregulation In Graft Survival In Autoimmunity, Bhagirath Singh
Role Of Mhc Antigens And Immunoregulation In Graft Survival In Autoimmunity, Bhagirath Singh
Microbiology & Immunology Publications
Using a syngeneic islet transplantation model system we have showed that in autoimmune type 1 diabetes transplanted islets are destroyed by the host immune system unless the transplanted islets lack class I major histocompatibility complex (MHC) molecules. Alternatively, immunomodulation of the host by induction of regulatory T cells prevented the destruction of autologous islet graft. We conclude that these approaches will allow successful transplantation of autologous islets derived from the host by stem cell or other technology without immunosuppression to reverse autoimmune type 1 diabetes.
Morphological And Molecular Analyses Of Microorganisms In Caribbean Reef Adult Sponges And In Corresponding Reproductive Material, Susanne Schmitt, Markus Wehrl, Niels Lindquist, Jeremy B. Weisz, Ute Hentschel
Morphological And Molecular Analyses Of Microorganisms In Caribbean Reef Adult Sponges And In Corresponding Reproductive Material, Susanne Schmitt, Markus Wehrl, Niels Lindquist, Jeremy B. Weisz, Ute Hentschel
Faculty Publications
Caribbean reef sponges were surveyed for the presence of microorganisms in the mesohyl tissue of adult sponges and the respective reproductive material (embryos, larvae). A clear correlation was found in that high microbial abundance (HMA) sponges always contained microorganisms in their reproductive stages. In contrast, low microbial abundance (LMA) sponges did not contain microorganisms in their reproductive stages. Based on these data, Ircinia felix Duchassaing and Michelotti, 1864 was chosen as a model organism for the molecular analysis of microorganisms within the adult sponge and its larvae and juveniles. Denaturing gradient gel electrophoresis (DGGE) of eubacterial 16S rDNA sequences revealed …
Vertical Transmission Of A Phylogenetically Complex Microbial Consortium In The Viviparous Sponge Ircinia Felix, Susanne Schmitt, Jeremy B. Weisz, Niels Lindquist, Ute Hentschel
Vertical Transmission Of A Phylogenetically Complex Microbial Consortium In The Viviparous Sponge Ircinia Felix, Susanne Schmitt, Jeremy B. Weisz, Niels Lindquist, Ute Hentschel
Faculty Publications
Many marine demosponges contain large amounts of phylogenetically complex yet highly sponge-specific microbial consortia within the mesohyl matrix, but little is known about how these microorganisms are acquired by their hosts. Settlement experiments were performed with the viviparous Caribbean demosponge Ircinia felix to investigate the role of larvae in the vertical transmission of the sponge-associated microbial community. Inspections by electron microscopy revealed large amounts of morphologically diverse microorganisms in the center of I. felix larvae, while the outer rim appeared to be devoid of microorganisms. In juveniles, microorganisms were found between densely packed sponge cells. Denaturing gradient gel electrophoresis (DGGE) …
Poxviral B1 Kinase Overcomes Barrier To Autointegration Factor, A Host Defense Against Virus Replication, Matthew S. Wiebe, Paula Traktman
Poxviral B1 Kinase Overcomes Barrier To Autointegration Factor, A Host Defense Against Virus Replication, Matthew S. Wiebe, Paula Traktman
Nebraska Center for Virology: Faculty Publications
Barrier to autointegration factor (BAF) is a DNA-binding protein found in the nucleus and cytoplasm of eukaryotic cells that functions to establish nuclear architecture during mito-sis. Herein, we demonstrate a cytoplasmic role for BAF in host defense during poxviral infections. Vaccinia is the prototypic poxvirus, a family of DNA viruses that replicate ex-clusively in the cytoplasm of infected cells. Mutations in the vaccinia B1 kinase (B1) com-promise viral DNA replication, but the mechanism by which B1 achieves this has remained elusive. We now show that BAF acts as a potent inhibitor of poxvirus replication unless its DNA-binding activity is blocked …
Environmental Controls On The Landscape-Scale Biogeography Of Stream Bacterial Communities, Noah Fierer, Jennifer L. Morse, Sean T. Berthrong, Emily S. Bernhardt, Robert B. Jackson
Environmental Controls On The Landscape-Scale Biogeography Of Stream Bacterial Communities, Noah Fierer, Jennifer L. Morse, Sean T. Berthrong, Emily S. Bernhardt, Robert B. Jackson
Scholarship and Professional Work - LAS
We determined the biogeographical distributions of stream bacteria and the biogeochemical factors that best explained heterogeneity for 23 locations within the Hubbard Brook watershed, a 3000-ha forested watershed in New Hampshire, USA. Our goal was to assess the factor, or set of factors, responsible for generating the biogeographical patterns exhibited by microorganisms at the landscape scale. We used DNA fingerprinting to characterize bacteria inhabiting fine benthic organic matter (FBOM) because of their important influence on stream nutrient dynamics. Across the watershed, streams of similar pH had similar FBOM bacterial communities. Streamwater pH was the single variable most strongly correlated with …
Sulfur-Oxidizing Bacteria In Soap Lake (Washington State), A Meromictic, Haloalkaline Lake With An Unprecedented High Sulfide Content, Dimitry Y. Sorokin, Mirjam Foti, Holly C. Pinkart, Gerard Muyzer
Sulfur-Oxidizing Bacteria In Soap Lake (Washington State), A Meromictic, Haloalkaline Lake With An Unprecedented High Sulfide Content, Dimitry Y. Sorokin, Mirjam Foti, Holly C. Pinkart, Gerard Muyzer
All Faculty Scholarship for the College of the Sciences
Culture-dependent and -independent techniques were used to study the diversity of chemolithoautotrophic sulfur-oxidizing bacteria in Soap Lake (Washington State), a meromictic, haloalkaline lake containing an unprecedentedly high sulfide concentration in the anoxic monimolimnion. Both approaches revealed the dominance of bacteria belonging to the genus Thioalkalimicrobium, which are common inhabitants of soda lakes. A dense population of Thioalkalimicrobium (up to 107 cells/ml) was found at the chemocline, which is characterized by a steep oxygen-sulfide gradient. Twelve Thioalkalimicrobium strains exhibiting three different phenotypes were isolated in pure culture from various locations in Soap Lake. The isolates fell into two groups …
Aids-Associated Viral Oncogenesis: Overview, Charles Wood
Aids-Associated Viral Oncogenesis: Overview, Charles Wood
Nebraska Center for Virology: Faculty Publications
It has been 25 years since the acquired immunodeficiency syndrome (AIDS) was first described and over 23 years since the human immunodeficiency virus (HIV) associated with the disease was first discovered. In spite of the tremendous progress that was made in understanding both the disease and the virus, there are still millions of people infected, died, or living with the disease. As for the year 2005 alone, the Joint United Nations Programme on HIV/AIDS (http://www.UNAIDS.org) estimates that there are about 40 million people living with HIV/AIDS globally, and approximately 3 million people died from AIDS in the year. Globally, it …
Modulation Of Retroviral Restriction And Proteasome Inhibitor-Resistant Turnover By Changes In The Trim5Α B-Box 2 Domain, Felipe Diaz-Griffero, Alak Kar, Michel Perron, Shi-Hua Xiang, Hassan Javanbakht, Xing Li, Joseph Sodroski
Modulation Of Retroviral Restriction And Proteasome Inhibitor-Resistant Turnover By Changes In The Trim5Α B-Box 2 Domain, Felipe Diaz-Griffero, Alak Kar, Michel Perron, Shi-Hua Xiang, Hassan Javanbakht, Xing Li, Joseph Sodroski
Nebraska Center for Virology: Faculty Publications
An intact B-box 2 domain is essential for the antiretroviral activity of TRIM5α. We modeled the structure of the B-box 2 domain of TRIM5α based on the existing three-dimensional structure of the B-box 2 domain of human TRIM29. Using this model, we altered the residues predicted to be exposed on the surface of this globular structure. Most of the alanine substitutions in these residues exerted little effect on the antiretroviral activity of human TRIM5αhu or rhesus monkey TRIM5αrh. However, alteration of arginine 119 of TRIM5αhu or the corresponding arginine 121 of TRIM5αrh diminished the abilities of …
Viral Diseases Of The Fetus, Clayton L. Kelling
Viral Diseases Of The Fetus, Clayton L. Kelling
Nebraska Center for Virology: Faculty Publications
Bovine viral diarrhea virus (BVDV) is one of the most commonly encountered and economically important pathogens of cattle in North America. Since the mid-20th century, BVDV has been recognized as a significant cause of disease of the gastrointestinal system. The impact of BVDV on reproduction was not perceived for another 30 years, when the occurrence of persistent infection in imunotolerant cattle was described.
BVDV infections may occur in cattle as acute illness- that is, bovine viral diarrhea (BVD)-or as a generally chronic condition-mucosal disease. When susceptible regnant cattle are infected with BVDV, transplacental infections usually occur. Transplacental infections may lead …
Prion Interference Is Due To A Reduction In Strain-Specific PrpSc Levels, Jason C. Bartz, Michelle L. Kramer, Meghan H. Sheehan, Jessica A. L. Hutter, Jacob I. Ayers, Richard A. Bessen, Anthony E. Kincaid
Prion Interference Is Due To A Reduction In Strain-Specific PrpSc Levels, Jason C. Bartz, Michelle L. Kramer, Meghan H. Sheehan, Jessica A. L. Hutter, Jacob I. Ayers, Richard A. Bessen, Anthony E. Kincaid
Nebraska Center for Virology: Faculty Publications
When two prion strains infect a single host, one strain can interfere with the ability of the other to cause disease but it is not known whether prion replication of the second strain is also diminished. To further investigate strain interference, we infected hamsters in the sciatic nerve with the long-incubation-period transmissible mink encephalopathy (TME) agent DY TME prior to superinfection of hamsters with the short-incubation-period HY TME agent. Increases in the interval between TME agent inoculations resulted in an extension of the incubation period of HY TME or a complete block of the ability of the HY TME agent …
Traditional Practices And Exposure To Bodily Fluids In Lusaka, Zambia, Janet M. Wojcicki, Chipepo Kankasa, Charles Mitchell, Charles Wood
Traditional Practices And Exposure To Bodily Fluids In Lusaka, Zambia, Janet M. Wojcicki, Chipepo Kankasa, Charles Mitchell, Charles Wood
Papers in Virology
Objectives To ascertain if there are specific sociocultural and behavioral practices associated with the exposure to saliva, semen and vaginal fluids, particularly through child-rearing practices and the use of traditional medicine in Lusaka, Zambia. Methods We conducted 11 focus group discussions with men and women from diverse ethnic and socioeconomic backgrounds (n = 105) in Lusaka, Zambia in March 2004. We also conducted a brief sociodemographic survey of all focus group participants. Results Discussions indicated that saliva was used while engaging in home health care practices associated with childcare and the use of traditional medicine. Additionally, semen and vaginal …
Design Of A Bioreactor To Study The Role Of Red Blood Cells In The Transport Of Nitric Oxide In The Microcirculation, Nupura Bhise, Mahendra Kavdia
Design Of A Bioreactor To Study The Role Of Red Blood Cells In The Transport Of Nitric Oxide In The Microcirculation, Nupura Bhise, Mahendra Kavdia
Discovery, The Student Journal of Dale Bumpers College of Agricultural, Food and Life Sciences
Nitric oxide (NO) plays an important role in physiological functions like vasodilation, neurotransmission, and inhibition of platelet aggregation. The endothelium-derived NO diffuses into the vascular lumen where it interacts with flowing blood as well as the smooth muscles where it modulates vascular tone. However, uncertainty exists on how NO escapes the rapid scavenging by hemoglobin (Hb) and reaches smooth muscles. Several proposed hypotheses include 1) a reduced reaction rate of NO with Hb contained inside red blood cells (RBCs) and 2) NO preservation in the bound form of s-nitrosohemoglobin or nitrite. The mechanism and magnitude of reduction of NO reaction …
Extending And Measuring The Quality Of Fresh-Cut Fruit And Vegetables: A Review, Ana Belen Martin-Diana, Daniel Rico, Gary Henehan, Jesus Maria Frias, J. Barat
Extending And Measuring The Quality Of Fresh-Cut Fruit And Vegetables: A Review, Ana Belen Martin-Diana, Daniel Rico, Gary Henehan, Jesus Maria Frias, J. Barat
Articles
The market sales of ready - to - use vegetables have grown rapidly in recent decades as a result of changes in consumer attitudes especially consumption of fresh-cut lettuce and carrot due to their use in prepared salads. Chlorine solutions have been widely used to sanitise fruit and vegetables in the fresh-cut industry. However, the association of chlorine with the possible formation of carcinogenic chlorinated compounds in water has called into question the use of chlorine in food processing. There is a real need to find alternatives for preservation of fresh-cut fruit and vegetables in order to improve the efficacy …
Humboldt Journal Of Microbiology: Volume 9, Number 1- May 2007, Press Humboldt
Humboldt Journal Of Microbiology: Volume 9, Number 1- May 2007, Press Humboldt
Humboldt Journal of Microbiology
No abstract provided.
Comparison Study Of The Averaged Sediment Microbial Enzyme Activities In Four Fecally-Contaminated Streams In The Same Watershed In Northeast Tennessee To Biochemical Oxygen Demand, Nitrate Concentration, And Phosphate Concentration, Brian G. Evanshen, Kurt J. Maier, Phillip R. Scheuerman
Comparison Study Of The Averaged Sediment Microbial Enzyme Activities In Four Fecally-Contaminated Streams In The Same Watershed In Northeast Tennessee To Biochemical Oxygen Demand, Nitrate Concentration, And Phosphate Concentration, Brian G. Evanshen, Kurt J. Maier, Phillip R. Scheuerman
ETSU Faculty Works
Microbial enzyme activities (MEA’s) are measurements of microbial metabolism. These activities are dependent on the need for nutrients and respiration. This extended study evaluated four streams in the same watershed that had an approved fecal coliform Total Maximum Daily Load. Sediment and water samples were collected monthly for the first year of each specific stream study, and then quarterly to the end of 2006. Dehydrogenase, a measure of microbial respiration, along with acid phosphatase, alkaline phosphatase, galactosidase and glucosidase activities were measured using colorimetric assays. Biochemical oxygen demand (BOD) was determined using the standard 5-day test (BOD5). Nitrate …
Evaluation Of Four Novel Broad-Host-Range Antimicrobial Agents., Jiahui Guo
Evaluation Of Four Novel Broad-Host-Range Antimicrobial Agents., Jiahui Guo
Theses
The overall objective of this thesis was to evaluate the antimicrobial effects of four novel broad-host-range antimicrobial agents. The first was a milk-derived lipoprotein developed by Westgate Biologicals with the support of Enterprise Ireland. This lipoprotein which was designated LactiSAL, was evaluated against a wide range of bacterial species associated with humans. Essentially, the LactiSAL was incorporated at a variety of concentrations into agar media, which were appropriate for cultivation of the different genera. Agars were examined for colony formation, after which it was possible to quantify the minimal inhibitory concentration for each genus. Subsequently, LactiSAL was incorporated at levels …
Hypoxic Induction And The Role Of Hifs In The Activation Of Luciferase Constitutive Reporters In Placental Stem Cells, Diane Michelle Doran
Hypoxic Induction And The Role Of Hifs In The Activation Of Luciferase Constitutive Reporters In Placental Stem Cells, Diane Michelle Doran
Browse all Theses and Dissertations
Hypoxia is critically important to the development of the embryo and placenta. Proper placental development is critical for normal fetal growth and embryonic survival. Abnormal placental development has been implicated in numerous obstetric complications, including preeclampsia, which affects about 7% of all pregnancies and can be fatal for both mother and baby. Rodent and murine trophoblast stem cells differentiate into three distinct cell lineages: giant cells, spongiotrophoblasts, and labyrinthine cells, which form different layers and have different functions within the placenta. Recent studies in our laboratory have focused on the invasive giant cell layer using the rodent Rcho-1 choriocarcinoma stem …
On A Multinational Assessment Of Rotavirus Disease In Europe, David O. Matson
On A Multinational Assessment Of Rotavirus Disease In Europe, David O. Matson
Community & Environmental Health Faculty Publications
Rotaviruses were discovered in the 1960s in animals and in the 1970s in humans; the latter discovery was made by an intrepid group who performed duodenal biopsies on children with acute gastroenteritis (AGE) [1]. By the late 1970s, data already clearly indicated that rotavirus was the cause of the annual winter peak of AGE affecting young children, as well as a frequent cause of severe gastroenteritis in various animal species (e.g., [2–5]). Use of the retrospectroscope clarified or left as tantalizing the suggestion that rotaviruses were the cause of the annual “winter vomiting syndrome” first described in children in 1910 …
Potential For Stimulating Host Anti-Tumor Immune Response Via Rnai-Mediated Local Foxp3 Knockdown, N. Klaiber
Potential For Stimulating Host Anti-Tumor Immune Response Via Rnai-Mediated Local Foxp3 Knockdown, N. Klaiber
Chemistry & Biochemistry Faculty Publications
Neoplastic growths represent a unique challenge for the host immune system. As they are indeed derived from self, many of the same mechanisms operating to prevent autoimmunity also provide an umbrella beneath which malignant cells are free to proliferate.1 Central among these immune regulatory boundaries are an influential subset of lymphocytes known as T regs. Hypothesized to exist decades ago, yet eluding definitive characterization until relatively recently, T regs have been demonstrated to play a crucial role in the proper functioning of the immune system as a whole. They may also, however, represent one of the primary obstacles to successful …
Mutations In Transmembrane Domains 1, 4 And 9 Of The Plasmodium Falciparum Chloroquine Resistance Transporter Alter Susceptibility To Chloroquine, Quinine And Quinidine, Roland A. Cooper, Kristan D. Lane, Bingbing Deng, Jianbing Mu, Jigar J. Patel, Thomas E. Wellems, Xinzhuan Su, Michael T. Ferdig
Mutations In Transmembrane Domains 1, 4 And 9 Of The Plasmodium Falciparum Chloroquine Resistance Transporter Alter Susceptibility To Chloroquine, Quinine And Quinidine, Roland A. Cooper, Kristan D. Lane, Bingbing Deng, Jianbing Mu, Jigar J. Patel, Thomas E. Wellems, Xinzhuan Su, Michael T. Ferdig
Biological Sciences Faculty Publications
Mutations in the Plasmodium falciparum chloroquine (CQ) resistance transporter (PfCRT) can result in verapamil-reversible CQ resistance and altered susceptibility to other antimalarials. PfCRT contains 10 membrane-spanning domains and is found in the digestive vacuole (DV) membrane of intraerythrocytic parasites. The mechanism by which PfCRT mediates CQ resistance is unclear although it is associated with decreased accumulation of drug within the DV. On the permissive background of the P. falciparum 106/1(K76) parasite line, we used single-step drug selection to generate isogenic clones containing unique pfcrt point mutations that resulted in amino acid changes in PfCRT transmembrane domains 1 (C72R, K76N, K76I …
Sensory Genes And Mate Choice: Evidence That Duplications, Mutations, And Adaptive Evolution Alter Variation In Mating Cue Genes And Their Receptors, Lisa Horth
Biological Sciences Faculty Publications
Fascinating new data, revealed through gene sequencing, comparative genomics, and genetic engineering, precisely establish which genes are involved in mate choice and mating activity—behaviors that are surprisingly understudied from a genetic perspective. Discussed here are some of the recently identified visual and chemosensory genes that are involved in mate choice and mating behavior. These genes’ products are involved in the production, transmission, and receipt of crucial sensory mate-choice cues that affect fitness. This review exposes newfound evidence that alternative splicing, gene-expression pattern changes, and molecular genetic variation in sensory genes are crucial for both intra- and interspecific mate choice and …
Design, Synthesis, And Evaluation Of 10-N-Substituted Acridones As Novel Chemosensitizers In Plasmodium Falciparum, Jane X. Kelly, Martin J. Smilkstein, Roland A. Cooper, Kristin D. Lane, Robert A. Johnson, Aaron Janowsky, Rozalia A. Dodean, David J. Hinrichs, Rolf Winter, Michael Riscoe
Design, Synthesis, And Evaluation Of 10-N-Substituted Acridones As Novel Chemosensitizers In Plasmodium Falciparum, Jane X. Kelly, Martin J. Smilkstein, Roland A. Cooper, Kristin D. Lane, Robert A. Johnson, Aaron Janowsky, Rozalia A. Dodean, David J. Hinrichs, Rolf Winter, Michael Riscoe
Biological Sciences Faculty Publications
A series of novel 10-N-substituted acridones, bearing alkyl side chains with tertiary amine groups at the terminal position, were designed, synthesized, and evaluated for the ability to enhance the potency of quinoline drugs against multidrug-resistant (MDR) Plasmodium falciparum malaria parasites. A number of acridone derivatives, with side chains bridged three or more carbon atoms apart between the ring nitrogen and terminal nitrogen, demonstrated chloroquine (CQ)-chemosensitizing activity against the MDR strain of P. falciparum (Dd2). Isobolograrn analysis revealed that selected candidates demonstrated significant synergy with CQ in the CQ-resistant (CQR) parasite Dd2 but only additive (or indifferent) interaction in the CQ-sensitive …
Chemical Defenses: From Compounds To Communities, Valerie J. Paul, Koty H. Sharp
Chemical Defenses: From Compounds To Communities, Valerie J. Paul, Koty H. Sharp
Arts & Sciences Faculty Publications
Marine natural products play critical roles in the chemical defense of many marine organisms and in some cases can influence the community structure of entire ecosystems. Although many marine natural products have been studied for biomedical activity, yielding important information about their biochemical effects and mechanisms of action, much less is known about ecological functions. The way in which marine consumers perceive chemical defenses can influence their health and survival and determine whether some natural products persist through a food chain. This article focuses on selected marine natural products, including okadaic acid, brevetoxins, lyngbyatoxin A, caulerpenyne, bryostatins, and isocyano terpenes, …
Characteristics Of A Foamy Virus-Derived Vector That Allow For Safe Autologous Gene Therapy To Correct Leukocyte Adhesion Deficiency Type 1, Ryan Matthew Mcnichol
Characteristics Of A Foamy Virus-Derived Vector That Allow For Safe Autologous Gene Therapy To Correct Leukocyte Adhesion Deficiency Type 1, Ryan Matthew Mcnichol
Browse all Theses and Dissertations
The hematopoeitic stem cell is a prime target for gene therapy in the attempt to correct a number of single gene inherited genetic defects that affect the immune system. In persons affected by leukocyte adhesion deficiency type 1 (LAD-1) the gene for the Beta-2 subunit of the integrin molecule is mutated. This autosomal recessive gene defect yields a phenotype with little or no beta-2 integrin expression on leukocytes. Beta-2 integrin expression is essential for leukocytes to travel from the blood to the tissues to fight infection. Persons with this disease have lowered leukocyte counts in the tissues and as a …
Hsv-1 Infection Of C3h Central Nervous System Cell Lines, Lauren Kay Van Buren
Hsv-1 Infection Of C3h Central Nervous System Cell Lines, Lauren Kay Van Buren
Browse all Theses and Dissertations
Herpes Simplex Virus Type 1 (HSV-1) can infect the nervous system, resulting in a disease known as herpes encephalitis (HSE). Herpes encephalitis affects thousands of people each year; many cases are fatal or permanently debilitating. Approximately two thousand known cases occur in the United States each year alone (Neuroland online source). Acyclovir has been the drug of choice used to treat herpes encephalitis. Even after the administration of acyclovir, permanent neurological damage and/or death often results. Thousands of individuals would benefit by the discovery of drugs that are more effective at preventing lasting HSE damage and death. Knowledge concerning HSE …
Discovery Of New Antimicrobial Agents Using Combinatorial Chemistry, William I. Northern
Discovery Of New Antimicrobial Agents Using Combinatorial Chemistry, William I. Northern
Browse all Theses and Dissertations
Combinatorial chemistry has become an important aspect of medicinal research due to its flexibility and the ability to produce large numbers of potential therapeutic agents. Once compounds are made, they must be screened to determine if there is any biological activity. This research project focused on developing a screening method for chemical agents produced by a graduate student in the chemistry department at Wright State University. After an acceptable screening method was found, the goal of the project was to determine if compounds produced had either antibacterial activity, antifungal activity, or both. Seven compounds exhibited biological activity. Two of these …
Structural Definition Of A Conserved Neutralization Epitope On Hiv-1 Gp120, Tongqing Zhou, Ling Xu, Barna Dey, Ann J. Hessell, Donald Van Ryk, Shi-Hua Xiang, Xinzhen Yang, Mei-Yun Zhang, Michael B. Zwick, James Arthos, Dennis R. Burton, Dimiter S. Dimitrov, Joseph Sodroski, Richard Wyatt, Gary J. Nabel, Peter D. Kwong
Structural Definition Of A Conserved Neutralization Epitope On Hiv-1 Gp120, Tongqing Zhou, Ling Xu, Barna Dey, Ann J. Hessell, Donald Van Ryk, Shi-Hua Xiang, Xinzhen Yang, Mei-Yun Zhang, Michael B. Zwick, James Arthos, Dennis R. Burton, Dimiter S. Dimitrov, Joseph Sodroski, Richard Wyatt, Gary J. Nabel, Peter D. Kwong
Nebraska Center for Virology: Faculty Publications
The remarkable diversity, glycosylation and conformational flexibility of the human immunodeficiency virus type 1 (HIV-1) envelope (Env), including substantial rearrangement of the gp120 glycoprotein upon binding the CD4 receptor, allow it to evade antibody-mediated neutralization. Despite this complexity, the HIV-1 Env must retain conserved determinants that mediate CD4 binding. To evaluate how these determinants might provide opportunities for antibody recognition, we created variants of gp120 stabilized in the CD4-bound state, assessed binding of CD4 and of receptor-binding-site antibodies, and determined the structure at 2.3Å resolution of the broadly neutralizing antibody b12 in complex with gp120. b12 binds to a conformationally …
Structures Of The Ccr5 N Terminus And Of A Tyrosine-Sulfated Antibody With Hiv-1 Gp120 And Cd4, Chih-Chin Huang, Son N. Lam, Priyamvada Acharya, Min Tang, Shi-Hua Xiang, Syed Shahzad-Ul Hussan, Robyn L. Stanfield, James Robinson, Ian A. Wilson, Richard Wyatt, Carole A. Bewley, Peter D. Kwong
Structures Of The Ccr5 N Terminus And Of A Tyrosine-Sulfated Antibody With Hiv-1 Gp120 And Cd4, Chih-Chin Huang, Son N. Lam, Priyamvada Acharya, Min Tang, Shi-Hua Xiang, Syed Shahzad-Ul Hussan, Robyn L. Stanfield, James Robinson, Ian A. Wilson, Richard Wyatt, Carole A. Bewley, Peter D. Kwong
Nebraska Center for Virology: Faculty Publications
The CCR5 co-receptor binds to the HIV-l gp120 envelope glycoprotein and facilitates HIV-l entry into cells. Its N terminus is tyrosine-sulfated, as are many antibodies that react with the co-receptor binding site on gp120. We applied nuclear magnetic resonance and crystallographic techniques to analyze the structure of the CCR5 N terminus and that of the tyrosine-sulfated antibody 412d in complex with gp120 and CD4. The conformations of tyrosine-sulfated regions of CCR5 (α-helix) and 412d (extendedloop) are surprisingly different. Nonetheless, a critical sulfotyrosine on CCR5 and on 412d induces similar structural rearrangements in gp120. These results now provide a framework for …
Functional Interplay Between The B-Box 2 And The B30.2(Spry) Domains Of Trim5Α, Xi Ling, Byeongwoon Song, Shi-Hua Xiang, Joseph Sodroski
Functional Interplay Between The B-Box 2 And The B30.2(Spry) Domains Of Trim5Α, Xi Ling, Byeongwoon Song, Shi-Hua Xiang, Joseph Sodroski
Nebraska Center for Virology: Faculty Publications
The retroviral restriction factors, TRIM5α and TRIMCyp, consist of RING and B-box 2 domains separated by a coiled coil from carboxy-terminal domains. These carboxy-terminal domains (the B30.2(SPRY) domain in TRIM5α and the cyclophilin A domain in TRIMCyp) recognize the retroviral capsid. Here we show that some B-box 2 changes in TRIM5α, but not in TRIMCyp, resulted in decreased human immunodeficiency virus (HIV-1) capsid binding. The phenotypic effects of these B-box 2 changes on the restriction of retroviral infection depended on the potency of restriction and the affinity of the TRIM5α interaction with the viral capsid, two properties specified by the …
Characterization Of Human Immunodeficiency Virus Type 1 Monomeric And Trimeric Gp120 Glycoproteins Stabilized In The Cd4-Bound State: Antigenicity, Biophysics, And Immunogenicity, Barna Dey, Marie Pancera, Krisha Svehla, Yuuei Shu, Shi-Hua Xiang, Jeffrey Vainshtein, Yuxing Li, Joseph Sodroski, Peter D. Kwong, John R. Mascola, Richard Wyatt
Characterization Of Human Immunodeficiency Virus Type 1 Monomeric And Trimeric Gp120 Glycoproteins Stabilized In The Cd4-Bound State: Antigenicity, Biophysics, And Immunogenicity, Barna Dey, Marie Pancera, Krisha Svehla, Yuuei Shu, Shi-Hua Xiang, Jeffrey Vainshtein, Yuxing Li, Joseph Sodroski, Peter D. Kwong, John R. Mascola, Richard Wyatt
Nebraska Center for Virology: Faculty Publications
The human immunodeficiency virus type 1 exterior gp120 envelope glycoprotein is highly flexible, and this flexibility may contribute to the inability of monomeric gp120 immunogens to elicit broadly neutralizing antibodies. We previously showed that an S375W modification of a critical interfacial cavity central to the primary receptor binding site, the Phe43 cavity, stabilizes gp120 into the CD4-bound state. However, the immunological effects of this cavity-altering replacement were never tested. Subsequently, we screened other mutations that, along with the S375W alteration, might further stabilize the CD4-bound state. Here, we define a selected second cavity-altering replacement, T257S, and analyze the double mutations …