Medical Specialties Commons^™

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 …

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 TRIM5α_rh. However, alteration of arginine 119 of TRIM5α_hu or the corresponding arginine 121 of TRIM5α_rh diminished the abilities of …

Dengue Virus Serotype 3, Karachi, Pakistan, Bushra Jamil, Rumina Hasan, Afia Zafar, Kevin Bewley, John Chamberlain, Valerie Mioulet, Moira Rowlands, Roger Hewson

Department of Medicine

No abstract provided.

Outcomes Of Peginterferon Alfa-2a And Ribavirin Combination Therapy In A Resident-Initiated, Multidisciplinary, Hepatitis C Clinic, Nicole M. Agostino Do, Erini Vasiliadis Do, K Nadeem Ahmed Md, Suzanne J. Templer Do, Edward R. Norris Md, Fapa, Fapm, Charles M. Brooks Md, Eric J. Gertner Md, Mph, Joseph L. Yozviak Do, Facp

Department of Medicine

No abstract provided.

Knowledge And Beliefs Of Adolescents Regarding Sexually Transmitted Infections And Hiv/Aids In A Rural District In Pakistan, Hafsa Raheel, Franklin White, Muhammad Masood Kadir, Zafar Fatmi

Community Health Sciences

Objective:

To assess the knowledge and beliefs of adolescents (15-19 years girls and boys) regarding sexually transmitted infections (STIs) and HIV/AIDS.

Methods:

A community based cross-sectional survey was conducted in October 2002 in a rural district (Mirpurkhas) of Sindh province, Pakistan.

Results:

A total of 428 adolescent girls and boys were interviewed. Only 44% correctly named at least one STI, while 55% knew at least two modes of transmission for HIV/AIDS. Adolescents with education greater than or equal to secondary level, those who were able to read the newspaper, possessed electricity in their homes and were allowed to meet their …

Resource Allocation Within The National Aids Control Program Of Pakistan: A Qualitative Assessment Of Decision Maker's Opinions, Sara Husain, Masood Kadir, Zafar Fatmi

Community Health Sciences

Background:

Limited resources, whether public or private, demand prioritisation among competing needs to maximise productivity. With a substantial increase in the number of reported HIV cases, little work has been done to understand how resources have been distributed and what factors may have influenced allocation within the newly introduced Enhanced National AIDS Control Program of Pakistan. The objective of this study was to identify perceptions of decision makers about the process of resource allocation within Pakistan's Enhanced National AIDS Control Program.

Methods:

A qualitative study was undertaken and in-depth interviews of decision makers at provincial and federal levels responsible to …

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

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 …

Georgeoral Immunization Of Rhesus Macaques With Adenoviral Hiv Vaccines Using Enteric-Coated Capsules, George T. Mercier, Pramod N. Nehete, Marco F. Passeri, Bharti N. Nehete, Eric A. Weaver, Nancy Smyth Templeton, Kimberly Schluns, Stephanie S. Buchl, K. Jagannadha Sastry, Michael A. Barry

Nebraska Center for Virology: Faculty Publications

Targeted delivery of vaccine candidates to the gastrointestinal (GI) tract holds potential for mucosal immunization, particularly against mucosal pathogens like the human immunodeficiency virus (HIV). Among the different strategies for achieving targeted release in the GI tract, namely the small intestine, pH sensitive enteric coating polymers have been shown to protect solid oral dosage forms from the harsh digestive environment of the stomach and dissolve relatively rapidly in the small intestine by taking advantage of the luminal pH gradient. We developed an enteric polymethacrylate formulation for coating hydroxy-propyl-methyl-cellulose (HPMC) capsules containing lyophilized Adenoviral type 5 (Ad5) vectors expressing HIV-1 gag …

Planning An Integrated Disease Surveillance And Response System: A Matrix Of Skills And Activities, Helen N. Perry, Sharon M. Mcdonnell, Wondimagegnehu Alemu, Peter Nsubuga

Dartmouth Scholarship

The threat of a global influenza pandemic and the adoption of the World Health Organization (WHO) International Health Regulations (2005) highlight the value of well-coordinated, functional disease surveillance systems. The resulting demand for timely information challenges public health leaders to design, develop and implement efficient, flexible and comprehensive systems that integrate staff, resources, and information systems to conduct infectious disease surveillance and response. To understand what resources an integrated disease surveillance and response system would require, we analyzed surveillance requirements for 19 priority infectious diseases targeted for an integrated disease surveillance and response strategy in the WHO African region.

Up-Regulation Of Interferon-A/Apobec3g Signal Pathway Potently Inactivates Hiv-1 Infectivity In Resting Cd4-T Cells, Keyang Chen, Jialing Huang, Chune Zhang, Sophia Huang, Giuseppe Nunnari, Feng-Xiang Wang, Xiangrong Tong, Ling Gao, Kristi Nikisher, Hui Zhang

Department of Medicine Faculty Papers

Poster Presentation.

Treatment Of Spinal Tuberculosis: Role Of Surgical Intervention, Ather Enam, Ahmed Ali Shah

Section of Neurosurgery

The treatment of tuberculosis of the spine (Pott's disease) is essentially conservative and a vast majority of patients can be successfully managed on antituberculo us therapy (ATT) alone.1 Surgery is indicated in a few specific cases where deformity of spine, pain, or neurological compromise is becoming a serious issue. In cases where surgery is indicated the benefits are almost immediate and excellent. Tuberculosis (TB) is one of the leading causes of infectious disease-related deaths in under-developed countries and it has had a resurgence in developed countries as well. The most common site of bony dissemination of this disease is in …

Psychiatric Outcomes In A Resident-Run, Multidisciplinary, Hepatitis C Clinic (Poster), Nicole M. Agostino Do, Edward Norris Md, Fapm, Joseph L. Yozviak Do, Facp, Suzanne J. Templer Do, Charles M. Brooks Md, Eric J. Gertner Md, Mph, Michael Kaufmann Md

Department of Medicine

No abstract provided.

A Survey Of Primary Care Residents Regarding Knowledge Of Hepatitis C, Joseph L. Yozviak Do, Facp, Erini Vasiliadis Do, Sharon R. Kimmel Phd, Mha, Suzanne J. Templer Do, Margaret Hoffman-Terry Md, Facp

Department of Medicine

No abstract provided.

Transcutaneous Immunization With Toxin-Coregulated Pilin A Induces Protective Immunity Against Vibrio Cholerae O1 El Tor Challenge In Mice, Julianne E. Rollenhagen, Anuj Kalsy, Francisca Cerda, Manohar John

Dartmouth Scholarship

Toxin-coregulated pilin A (TcpA) is the main structural subunit of a type IV bundle-forming pilus of Vibrio cholerae, the cause of cholera. Toxin-coregulated pilus is involved in formation of microcolonies of V. cholerae at the intestinal surface, and strains of V. cholerae deficient in TcpA are attenuated and unable to colonize intestinal surfaces. Anti-TcpA immunity is common in humans recovering from cholera in Bangladesh, and immunization against TcpA is protective in murine V. cholerae models. To evaluate whether transcutaneously applied TcpA is immunogenic, we transcutaneously immunized mice with 100 mug of TcpA or TcpA with an immunoadjuvant (cholera toxin [CT], …

Prophylaxis And Therapy Of Inhalational Anthrax By A Novel Monoclonal Antibody To Protective Antigen That Mimics Vaccine-Induced Immunity, Laura Vitale, Diann Blanset, Israel Lowy, Thomas O'Neill, Joel Goldstein, Stephen F. Little, Gerard P. Andrews, Gary Dorough, Ronald K. Taylor, Tibor Keler

Dartmouth Scholarship

The neutralizing antibody response to the protective antigen (PA) component of anthrax toxin elicited by approved anthrax vaccines is an accepted correlate for vaccine-mediated protection against anthrax. We reasoned that a human anti-PA monoclonal antibody (MAb) selected on the basis of superior toxin neutralization activity might provide potent protection against anthrax. The fully human MAb (also referred to as MDX-1303 or Valortim) was chosen from a large panel of anti-PA human MAbs generated using transgenic mice immunized with recombinant PA solely on the basis of in vitro anthrax toxin neutralization. This MAb was effective in prophylactic and postsymptomatic treatment of …

Cd80 And Cd86 Control Antiviral Cd8+ T-Cell Function And Immune Surveillance Of Murine Gammaherpesvirus 68, Shinichiro Fuse, Joshua J. Obar, Sarah Bellfy, Erica K. Leung, Weijun Zhang, Edward J. Usherwood

Dartmouth Scholarship

The interactions between CD80 and CD86 on antigen-presenting cells and CD28 on T cells serve as an important costimulatory signal in the activation of T cells. Although the simplistic two-signal hypothesis has been challenged in recent years by the identification of different costimulators, this classical pathway has been shown to significantly impact antiviral humoral and cellular immune responses. How the CD80/CD86-CD28 pathway affects the control of chronic or latent infections has been less well characterized. In this study, we investigated its role in antiviral immune responses against murine gammaherpesvirus 68 (MHV-68) and immune surveillance using CD80/CD86^−/− mice. In the …

Expanding Access To Care Through A Resident-Initiated Hepatitis C Clinic - An Innovative Method For Incorporating Acgme Core Competencies Into The Management Of Medically Underserved Patients, Joseph L. Yozviak Do, Facp, Suzanne J. Templer Do, Erini Vasiliadis Do, Vishal Patel Md, Nicole M. Agostino Do, K Nadeem Ahmed Md, Edward Norris Md, Fapm, Charles M. Brooks Md, Eric J. Gertner Md, Mph

Department of Medicine

No abstract provided.

Cross-Subtype T-Cell Immune Responses Induced By A Human Immunodeficiency Virus Type 1 Group M Consensus Env Immunogen†0--, Eric A. Weaver, Zhongjing Lu, Zenaido T. Camacho, Fatiha Moukdar, Hua-Xin Liao, Ben-Jiang Ma, Mark Muldoon, James Theiler, Gary J. Nabel, Norman L. Letvin, Bette T. Korber, Beatrice H. Hahn, Barton F. Haynes, Feng Gao

Nebraska Center for Virology: Faculty Publications

The genetic diversity among globally circulating human immunodeficiency virus type 1 (HIV-1) strains is a serious challenge for HIV-1 vaccine design. We have generated a synthetic groupMconsensus env gene (CON6) for induction of cross-subtype immune responses and report here a comparative study of T-cell responses to this and natural strain env immunogens in a murine model. Three different strains of mice were immunized with CON6 as well as subtype A, B, or C env immunogens, using a DNA prime-recombinant vaccinia virus boost strategy. T-cell epitopes were mapped by gamma interferon enzyme-linked immunospot analysis using five overlapping Env peptide sets from …

Historical Lassa Fever Reports And 30-Year Clinical Update, Abe M. Macher, Martin S. Wolfe

Medicine Faculty Publications

Five cases of Lassa fever have been imported from West Africa to the United States since 1969. We report symptoms of the patient with the second imported case and the symptoms and long-term follow-up on the patient with the third case. Vertigo in this patient has persisted for 30 years.

Staphylococcus Aureus Escapes More Efficiently From The Phagosome Of A Cystic Fibrosis Bronchial Epithelial Cell Line Than From Its Normal Counterpart, Todd M. Jarry, Ambrose L. Cheung

Dartmouth Scholarship

Staphylococcus aureus is frequently the initial bacterium isolated from young cystic fibrosis (CF) patients, and yet its role in CF disease progression has not been determined. Recent data from our lab demonstrates that S. aureus can invade and replicate within the CF tracheal epithelial cell line (CFT-1). Here we describe the finding that the fate of internalized S. aureus in CFT-1 cells differs from its complemented counterpart (LCFSN). S. aureus strain RN6390 was able to replicate within the mutant CFT-1 cells after invasion but not in the complemented LCFSN cells. At 1 h postinvasion, S. aureus containing vesicles within both …

Keeping Their Options Open: Acute Versus Persistent Infections, S. Furukawa, S. L. Kuchma, G. A. O'Toole

Dartmouth Scholarship

No abstract provided.

Do Cd1-Restricted T Cells Contribute To Antibody-Mediated Immunity Against Mycobacterium Tuberculosis?, Mark L. Lang, Aharona Glatman-Freedman

Dartmouth Scholarship

No abstract provided.

Investigation Of Cell Surface Phenotypes At Mucosal Sites In Response To Murine Cytomegalovirus Infection, Mary Esther Bruorton

MUSC Theses and Dissertations

The salivary gland is the predominant effector site of mucosal immune responses in the oral cavity. In mice, the salivary glands are known to receive immune lymphocytes stimulated in inductive sites such as the gut- and nasal-associated lymphoid tissues, thus, allowing the production of antigen-specific antibodies in saliva. However, the potential of the salivary gland as a mucosal inductive site has not been fully explored. In order to investigate this concept, we have developed a model resulting in a focused salivary gland infection using intraglandular delivery of tissue culture-derived murine cytomegalovirus (tcMCMV). Utilizing this route of infection, we were capable …

A Group M Consensus Envelope Glycoprotein Induces Antibodies That Neutralize Subsets Of Subtype B And C Hiv-1 Primary Viruses, Hua-Xin Lin, Laura L. Sutherland, Shi-Mao Xia, Mary E. Brock, Richard M. Scearce, Stacie Vanleeuwen, S. Munir Alam, Mildred Mcadams, Eric A. Weaver, Zenaido T. Camacho, Ben-Jiang Ma, Yingying Li, Julie M. Decker, Gary J. Nabel, David C. Montefiori, Beatrice H. Hahn, Bette T. Korber, Feng Gao, Barton F. Haynes

Nebraska Center for Virology: Faculty Publications

HIV-1 subtype C is the most common HIV-1 group M subtype in Africa and many parts of Asia. However, to date HIV-1 vaccine candidate immunogens have not induced potent and broadly neutralizing antibodies against subtype C primary isolates. We have used a centralized gene strategy to address HIV-1 diversity, and generated a group M consensus envelope gene with shortened consensus variable loops (CON-S) for comparative studies with wildtype (WT) Env immunogens. Our results indicate that the consensus HIV-1 group M CON-S Env elicited cross-subtype neutralizing antibodies of similar or greater breadth and titer than the WT Envs tested, indicating the …

Innate Antiviral Response Targets Hiv-1 Release By The Induction Of Ubiquitin-Like Protein Isg15, Atsushi Okumura, Gengshi Lu, Ian Pitha-Rowe, Paula M. Pitha

Dartmouth Scholarship

The goal of this study was to elucidate the molecular mechanism by which type I IFN inhibits assembly and release of HIV-1 virions. Our study revealed that the IFN-induced ubiquitin-like protein ISG15 mimics the IFN effect and inhibits release of HIV-1 virions without having any effect on the synthesis of HIV-1 proteins in the cells. ISG15 expression specifically inhibited ubiquitination of Gag and Tsg101 and disrupted the interaction of the Gag L domain with Tsg101, but conjugation of ISG15 to Gag or Tsg101 was not detected. The inhibition of Gag-Tsg101 interaction was also detected in HIV-1 infected, IFN-treated cells. Elimination …

Design Clues From Functional Constraints And Broadly Neutralizing Antibodies, Tongqing Zhou, Ling Xu, Barna Dey, Ann J. Hessell, Shahzad Majeed, 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

No abstract provided.

Cross-Subtype T-Cell Immune Responses Induced By A Human Immunodeficiency Virus Type 1 Group M Consensus Env Immunogen, Eric A. Weaver, Zenaido T. Camacho, Fatiha Moukdar, Hua-Xin Liao, Ben-Jiang Ma, Mark Muldoon, James Theiler, Gary J. Nabel, Norman L. Letvin, Bette T. Korber, Beatrice H. Hahn, Barton F. Haynes, Feng Gao, Zhongjing Lu

Nebraska Center for Virology: Faculty Publications

The genetic diversity among globally circulating human immunodeficiency virus type 1 (HIV-1) strains is a serious challenge for HIV-1 vaccine design. We have generated a synthetic group M consensus env gene (CON6) for induction of cross-subtype immune responses and report here a comparative study of T-cell responses to this and natural strain env immunogens in a murine model. Three different strains of mice were immunized with CON6 as well as subtype A, B, or C env immunogens, using a DNA prime-recombinant vaccinia virus boost strategy. T-cell epitopes were mapped by gamma interferon enzyme-linked immunospot analysis using five overlapping Env peptide …

Orally Delivered, Plant-Produced Tat Protein Primes Mice For A Challenge Dna Vaccine Expressing Tat, A V. Karasev, S Foulke, C Wellens, I Zwierzynski, R Baldwin, H Koprowski, M S. Reitz Jr

Department of Microbiology and Immunology Faculty Papers

Oral Presentation.

Antiviral Agents For Pregnant Women With Genital Herpes, Christopher Wenner Md

Articles

Clinical Question

Do antiviral medications prevent perinatal transmission of genital herpes to neonates?

Evidence-Based Answer

There is no evidence that the use of antiviral agents in women who are pregnant and have a history of genital herpes prevents perinatal transmission of herpes simplex virus (HSV) to neonates. [Strength of recommendation: A, based on multiple systematic reviews] However, treatment with antivirals during the last month of pregnancy does reduce the rate of HSV outbreaks in pregnant women and the resultant need for cesarean delivery. [Strength of recommendation: A, based on multiple systematic reviews]