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Full-Text Articles in Virology

Poxviral B1 Kinase Overcomes Barrier To Autointegration Factor, A Host Defense Against Virus Replication, Matthew S. Wiebe, Paula Traktman Jan 2007

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 …


Aids-Associated Viral Oncogenesis: Overview, Charles Wood Jan 2007

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 Jan 2007

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 Jan 2007

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 Jan 2007

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 …


A Protein Encoded By The Bovine Herpesvirus 1 Latency-Related Gene Interacts With Specific Cellular Regulatory Proteins, Including Ccaat Enhancer Binding Protein Alpha, Florencia Meyer, Sandra Perez, Vicki Geiser, Mark Sintek, Melissa Inman, Clinton J. Jones Jan 2007

A Protein Encoded By The Bovine Herpesvirus 1 Latency-Related Gene Interacts With Specific Cellular Regulatory Proteins, Including Ccaat Enhancer Binding Protein Alpha, Florencia Meyer, Sandra Perez, Vicki Geiser, Mark Sintek, Melissa Inman, Clinton J. Jones

Nebraska Center for Virology: Faculty Publications

Following acute infection, bovine herpesvirus 1 establishes latency in sensory neurons of trigeminal ganglia (TG). Reactivation from latency occurs periodically, resulting in the shedding of infectious virus. The latency-related (LR) RNA is abundantly expressed in TG of latently infected calves, and the expression of LR proteins is necessary for dexamethasone-induced reactivation from latency. Previously published studies also identified an alternatively spliced LR transcript which is abundantly expressed in TG at 7 days after infection and has the potential to encode a novel LR fusion protein. Seven days after infection is when extensive viral gene expression is extinguished in TG and …


Functional Interplay Between The B-Box 2 And The B30.2(Spry) Domains Of Trim5Α, Xi Ling, Byeongwoon Song, Shi-Hua Xiang, Joseph Sodroski Jan 2007

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 Jan 2007

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 Jan 2007

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 …


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 Jan 2007

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 Jan 2007

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 …


Genomeblast: A Web Tool For Small Genome Comparison, Guoqing Lu, Liying Jiang, Resa M. K. Helikar, Thaine W. Rowley, Luwen Zhang, Xianfeng Chen, Etsuko N. Moriyama Dec 2006

Genomeblast: A Web Tool For Small Genome Comparison, Guoqing Lu, Liying Jiang, Resa M. K. Helikar, Thaine W. Rowley, Luwen Zhang, Xianfeng Chen, Etsuko N. Moriyama

Nebraska Center for Virology: Faculty Publications

Background: Comparative genomics has become an essential approach for identifying homologous gene candidates and their functions, and for studying genome evolution. There are many tools available for genome comparisons. Unfortunately, most of them are not applicable for the identification of unique genes and the inference of phylogenetic relationships in a given set of genomes.

Results: GenomeBlast is a Web tool developed for comparative analysis of multiple small genomes. A new parameter called "coverage" was introduced and used along with sequence identity to evaluate global similarity between genes. With GenomeBlast, the following results can be obtained: (1) unique genes in each …


Molecularly Cloned Shiv-1157ipd3n4: A Highly Replication- Competent, Mucosally Transmissible R5 Simian-Human Immunodeficiency Virus Encoding Hiv Clade C Env, R. J. Song, A.-L. Chenine, R. A. Rasmussen, C. R. Ruprecht, S. Mirshahidi, D. R. Grisson, W. Xu, J. B. Whitney, L. M. Goins, H. Ong, P.-L. Li, E. Shai-Kobiler, T. Wang, C. M. Mccann, Hong Zhang, Charles Wood, C. Kankasa, W. E. Secor, H. M. Mcclure, E. Strobert, J. G. Else, R. M. Ruprecht Sep 2006

Molecularly Cloned Shiv-1157ipd3n4: A Highly Replication- Competent, Mucosally Transmissible R5 Simian-Human Immunodeficiency Virus Encoding Hiv Clade C Env, R. J. Song, A.-L. Chenine, R. A. Rasmussen, C. R. Ruprecht, S. Mirshahidi, D. R. Grisson, W. Xu, J. B. Whitney, L. M. Goins, H. Ong, P.-L. Li, E. Shai-Kobiler, T. Wang, C. M. Mccann, Hong Zhang, Charles Wood, C. Kankasa, W. E. Secor, H. M. Mcclure, E. Strobert, J. G. Else, R. M. Ruprecht

Nebraska Center for Virology: Faculty Publications

Human immunodeficiency virus type 1 (HIV-1) clade C causes >50% of all HIV infections worldwide, and an estimated 90% of all transmissions occur mucosally with R5 strains. A pathogenic R5 simian-human immunodeficiency virus (SHIV) encoding HIV clade Cenv is highly desirable to evaluate candidate AIDS vaccines in nonhuman primates. To this end, we generated SHIV-1157i, a molecular clone from a Zambian infant isolate that carries HIV clade C env. SHIV-1157i was adapted by serial passage in five monkeys, three of which developed peripheral CD44 T-cell depletion. After the first inoculated monkey developed AIDS at week 137 postinoculation, …


Genome Of Horsepox Virus, Gustavo A. Delhon, C. L. Afonso, Z. Lu, L. Zsak, N. T. Sandybaev, U. M. Kerembekova, V. L. Zaitsev, G. F. Kutish, D. L. Rock Sep 2006

Genome Of Horsepox Virus, Gustavo A. Delhon, C. L. Afonso, Z. Lu, L. Zsak, N. T. Sandybaev, U. M. Kerembekova, V. L. Zaitsev, G. F. Kutish, D. L. Rock

Nebraska Center for Virology: Faculty Publications

Here we present the genomic sequence of horsepox virus (HSPV) isolate MNR-76, an orthopoxvirus (OPV) isolated in 1976 from diseased Mongolian horses. The 212-kbp genome contained 7.5-kbp inverted terminal repeats and lacked extensive terminal tandem repetition. HSPV contained 236 open reading frames (ORFs) with similarity to those in other OPVs, with those in the central 100-kbp region most conserved relative to other OPVs. Phylogenetic analysis of the conserved region indicated that HSPV is closely related to sequenced isolates of vaccinia virus (VACV) and rabbitpox virus, clearly grouping together these VACV-like viruses. Fifty-four HSPV ORFs likely represented fragments of 25 orthologous …


Genome Of Invertebrate Iridescent Virus Type 3 (Mosquito Iridescent Virus), Gustavo A. Delhon, Edan R. Tulman, Claudio L. Afonso, Zhiqiang Lu, James J. Becnel, Bettina A. Moser, Gerald F. Kutish, Daniel L. Rock Sep 2006

Genome Of Invertebrate Iridescent Virus Type 3 (Mosquito Iridescent Virus), Gustavo A. Delhon, Edan R. Tulman, Claudio L. Afonso, Zhiqiang Lu, James J. Becnel, Bettina A. Moser, Gerald F. Kutish, Daniel L. Rock

Nebraska Center for Virology: Faculty Publications

Iridoviruses (IVs) are classified into five genera: Iridovirus and Chloriridovirus, whose members infect invertebrates, and Ranavirus, Lymphocystivirus, and Megalocytivirus, whose members infect vertebrates. Until now, Chloriridovirus was the only IV genus for which a representative and complete genomic sequence was not available. Here, we report the genome sequence and comparative analysis of a field isolate of Invertebrate iridescent virus type 3 (IIV-3), also known as mosquito iridescent virus, currently the sole member of the genus Chloriridovirus. Approximately 20% of the 190-kbp IIV-3 genome was repetitive DNA, with DNA repeats localized in 15 apparently noncoding regions. Of …


Virion-Associated Restriction Endonucleases Of Chloroviruses, Irina V. Agarkova, David Dunigan, James L. Van Etten Aug 2006

Virion-Associated Restriction Endonucleases Of Chloroviruses, Irina V. Agarkova, David Dunigan, James L. Van Etten

Nebraska Center for Virology: Faculty Publications

Chloroviruses are large, double-stranded-DNA, plaque-forming viruses that infect certain eukaryotic chlorella- like green algae. The prototype of the genus is Paramecium bursaria chlorella virus 1 (PBCV-1). Chlorovirus genomes contain various amounts of methylated nucleotides due to virus-encoded DNA methyltransferases (MTases); about 25% of the MTases are associated with companion DNA site-specific (restriction) endonucleases (REases). These enzymes constitute virally encoded restriction-modification (R/M) systems. Although several of the chlorovirus R/M systems are characterized, their biological functions are unknown. The PBCV-1 proteome reveals that two virus-encoded REases, but not their companion MTases, are virion associated, suggesting that viral REases might help degrade the …


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 Jul 2006

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 …


Genome Of Crocodilepox Virus, C. L. Afonso, E. R. Tulman, Gustavo A. Delhon, Z. Lu, G. J. Viljoen, D. B. Wallace, G. F. Kutish, D. L. Rock May 2006

Genome Of Crocodilepox Virus, C. L. Afonso, E. R. Tulman, Gustavo A. Delhon, Z. Lu, G. J. Viljoen, D. B. Wallace, G. F. Kutish, D. L. Rock

Nebraska Center for Virology: Faculty Publications

Here, we present the genome sequence, with analysis, of a poxvirus infecting Nile crocodiles (Crocodylus niloticus) (crocodilepox virus; CRV). The genome is 190,054 bp (62% G+C) and predicted to contain 173 genes encoding proteins of 53 to 1,941 amino acids. The central genomic region contains genes conserved and generally colinear with those of other chordopoxviruses (ChPVs). CRV is distinct, as the terminal 33-kbp (left) and 13-kbp (right) genomic regions are largely CRV specific, containing 48 unique genes which lack similarity to other poxvirus genes. Notably, CRV also contains 14 unique genes which disrupt ChPV gene colinearity within the …


Analysis Of Hiv-2 Vpx By Modeling And Insertional Mutagenesis, Lisa A. Mahnke, Michael Belshan, Lee Ratner Apr 2006

Analysis Of Hiv-2 Vpx By Modeling And Insertional Mutagenesis, Lisa A. Mahnke, Michael Belshan, Lee Ratner

Nebraska Center for Virology: Faculty Publications

Vpx facilitates HIV-2 nuclear localization by a poorly understood mechanism. We have compared Vpx to an NMR structure HIV- 1 Vpr in a central helical domain and probed regions of Vpx by insertional mutagenesis. A predicted loop between helices two and three appears to be unique, overlapping with a known novel nuclear localization signal. Overall, Vpx was found to be surprisingly flexible, tolerating a series of large insertions. We found that insertion within the polyproline-containing C-terminus destabilizes nuclear localization, whereas mutating a second helix in the central domain disrupts viral packaging. Other insertional mutants in the predicted loop and in …


Influence Of Bovine Respiratory Syncytial Virus F Glycoprotein N-Linked Glycans On In Vitro Expression And On Antibody Responses In Balb/C Mice, Holly A. Klink, Ryan Brady, Christina L. Topliff, Kent M. Eskridge, Subramaniam Srikumaran, Clayton L. Kelling Apr 2006

Influence Of Bovine Respiratory Syncytial Virus F Glycoprotein N-Linked Glycans On In Vitro Expression And On Antibody Responses In Balb/C Mice, Holly A. Klink, Ryan Brady, Christina L. Topliff, Kent M. Eskridge, Subramaniam Srikumaran, Clayton L. Kelling

Nebraska Center for Virology: Faculty Publications

Bovine respiratory syncytial virus (BRSV) is an etiological component of the bovine respiratory tract disease complex. Infection with BRSV following vaccination, or re-infection following natural infection is common since protection is incomplete. The objectives of this study were to create plasmid DNA constructs encoding single or multiple N-glycosylation-site deletion BRSV fusion (F) proteins, and evaluate their expression in cell culture, and potential to induce anti-BRSV F antibody responses in BALB/ c mice. Four plasmid DNAs were constructed, each encoding 1-4 N-glycosylation-site deletions: Gly4, Gly2/4, Gly1/2/4 and Gly1/2/3/4. Each of the N-glycosylation-site deletion BRSV F proteins were expressed …


The Latent Membrane Protein 1 Of Epstein-Barr Virus (Ebv) Primes Ebv Latency Cells For Type I Interferon Production, Dongsheng Xu, Kristen Brumm, Luwen Zhang Apr 2006

The Latent Membrane Protein 1 Of Epstein-Barr Virus (Ebv) Primes Ebv Latency Cells For Type I Interferon Production, Dongsheng Xu, Kristen Brumm, Luwen Zhang

Nebraska Center for Virology: Faculty Publications

Epstein-Barr virus (EBV) latency has been associated with a variety of human cancers. Latent membrane protein 1 (LMP-1) is one of the key viral proteins required for transformation of primary B cells in vitro and establishment of EBV latency. We have previously shown that LMP-1 induces the expression of several interferon (IFN)-stimulated genes and has antiviral effect (Zhang, J., Das, S. C., Kotalik, C., Pattnaik, A. K., and Zhang, L. (2004) J. Biol. Chem. 279, 46335–46342). In this report, a novel mechanism related to the antiviral effect of LMP-1 is identified. We show that EBV type III latency cells, in …


Influence Of N-Linked Glycosylation Of Porcine Reproductive And Respiratory Syndrome Virus Gp5 On Virus Infectivity, Antigenicity, And Ability To Induce Neutralizing Antibodies, Israrul H. Ansari, Byungjoon Kwon, Fernando A. Osorio, Asit K. Pattnaik Apr 2006

Influence Of N-Linked Glycosylation Of Porcine Reproductive And Respiratory Syndrome Virus Gp5 On Virus Infectivity, Antigenicity, And Ability To Induce Neutralizing Antibodies, Israrul H. Ansari, Byungjoon Kwon, Fernando A. Osorio, Asit K. Pattnaik

Nebraska Center for Virology: Faculty Publications

Porcine reproductive and respiratory syndrome virus (PRRSV) glycoprotein 5 (GP5) is the most abundant envelope glycoprotein and a major inducer of neutralizing antibodies in vivo. Three putative N-linked glycosylation sites (N34, N44, and N51) are located on the GP5 ectodomain, where a major neutralization epitope also exists. To determine which of these putative sites are used for glycosylation and the role of the glycan moieties in the neutralizing antibody response, we generated a panel of GP5 mutants containing amino acid substitutions at these sites. Biochemical studies with expressed wild-type (wt) and mutant proteins revealed that the mature GP5 contains high-mannose-type …


Characterization Of Functional Domains Of Equine Infectious Anemia Virus Rev Suggests A Bipartite Rna-Binding Domain, Jae-Hyung Lee, Sean C. Murphy, Michael Belshan, Wendy O. Sparks, Yvonne Wannemuehler, Sijun Liu, Thomas J. Hope, Drena Dobbs, Susan Carpenter Apr 2006

Characterization Of Functional Domains Of Equine Infectious Anemia Virus Rev Suggests A Bipartite Rna-Binding Domain, Jae-Hyung Lee, Sean C. Murphy, Michael Belshan, Wendy O. Sparks, Yvonne Wannemuehler, Sijun Liu, Thomas J. Hope, Drena Dobbs, Susan Carpenter

Nebraska Center for Virology: Faculty Publications

Equine infectious anemia virus (EIAV) Rev is an essential regulatory protein that facilitates expression of viral mRNAs encoding structural proteins and genomic RNA and regulates alternative splicing of the bicistronic tat/rev mRNA. EIAV Rev is characterized by a high rate of genetic variation in vivo, and changes in Rev genotype and phenotype have been shown to coincide with changes in clinical disease. To better understand how genetic variation alters Rev phenotype, we undertook deletion and mutational analyses to map functional domains and to identify specific motifs that are essential for EIAV Rev activity. All functional domains are contained within the …


Conserved Amino Acids Of The Human Immunodeficiency Virus Type 2 Vpx Nuclear Localization Signal Are Critical For Nuclear Targeting Of The Viral Preintegration Complex In Non-Dividing Cells, Michael Belshan, Lisa A. Mahnke, Lee Ratner Mar 2006

Conserved Amino Acids Of The Human Immunodeficiency Virus Type 2 Vpx Nuclear Localization Signal Are Critical For Nuclear Targeting Of The Viral Preintegration Complex In Non-Dividing Cells, Michael Belshan, Lisa A. Mahnke, Lee Ratner

Nebraska Center for Virology: Faculty Publications

The HIV-2 viral accessory protein Vpx is related to, but distinct from the Vpr protein of HIV-1. Vpx is packaged into virions and as a component of the viral preintegration complex (PIC) is required for efficient virus replication in non-dividing cells. We have previously reported that the minimal transferable region of Vpx that contained karyophilic properties was aa 65 to 72. Analysis of Vpx sequences from various HIV-2/SIV strains reveals that this region contains highly conserved amino acids, including two basic residues (K68, R70) and three tyrosines (Y66, Y69, Y71). Here, we demonstrate that mutation of the basic or tyrosine …


Uneven Distribution Of Mhc Class Ii Epitopes Within The Influenza Virus, Sherry R. Crowe, Shannon C. Miller, Pamela S. Adams, Richard Dutton, Allen G. Harmsen, Frances E. Lund, Troy D. Randall, Deborah M. Brown, Susan Swain, David L. Woodland Jan 2006

Uneven Distribution Of Mhc Class Ii Epitopes Within The Influenza Virus, Sherry R. Crowe, Shannon C. Miller, Pamela S. Adams, Richard Dutton, Allen G. Harmsen, Frances E. Lund, Troy D. Randall, Deborah M. Brown, Susan Swain, David L. Woodland

Nebraska Center for Virology: Faculty Publications

The identification of T cell epitopes is crucial for the understanding of the host immune response during infection. While much is known about the MHC class I-restricted response following influenza virus infection of C57BL/6 mice, with over 16 CD8 epitopes identified to date, less is known about the MHC class II-restricted response. Currently, only a few I-Ab-restricted T helper epitopes have been identified. Therefore, several important questions remain about how many class II epitopes exist in this system and whether these epitopes are evenly distributed within the most abundant viral proteins. In order to address these questions, we …


Factors Associated With Hiv Prevalence In A Pre-Partum Cohort Of Zambian Women, Janet S. St. Lawrence, W. Klaskala, C. Kankasa, J. T. West, Charles D. Mitchell, Charles Wood Jan 2006

Factors Associated With Hiv Prevalence In A Pre-Partum Cohort Of Zambian Women, Janet S. St. Lawrence, W. Klaskala, C. Kankasa, J. T. West, Charles D. Mitchell, Charles Wood

Nebraska Center for Virology: Faculty Publications

An ongoing study of mother-to-child human transmission in Zambian women (n = 3,160) allowed us to examine the association of medical injections with HIV serostatus while simultaneously accounting for other factors known to be correlated with HIV prevalence. Multi-method data collection included structured interviews, medical record abstraction, clinical examinations, and biological measures. Medically administered intramuscular or intravenous injections in the past five years (but not blood transfusions) were overwhelmmgly correlated with HIV prevalence, exceeding the contribution of sexual behaviors in a multivariable logistic regression. Statistically significant associations with HIV also were found for some demographic variables, sexual behaviors, alcohol …


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 Jan 2006

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 …


Characterization Of Hiv-1 Subtype C Envelope Glycoproteins From Perinatally Infected Children With Different Courses Of Disease, Hong Zhang, Federico Hoffmann, Jun He, Xiang He, Chipepo Kankasa, John T. West, Charles D. Mitchell, Ruth M. Ruprecht, Guillermo Orti, Charles Wood Jan 2006

Characterization Of Hiv-1 Subtype C Envelope Glycoproteins From Perinatally Infected Children With Different Courses Of Disease, Hong Zhang, Federico Hoffmann, Jun He, Xiang He, Chipepo Kankasa, John T. West, Charles D. Mitchell, Ruth M. Ruprecht, Guillermo Orti, Charles Wood

Nebraska Center for Virology: Faculty Publications

Background: The causal mechanisms of differential disease progression in HIV-1 infected children remain poorly defined, and much of the accumulated knowledge comes from studies of subtype B infected individuals. The applicability of such findings to other subtypes, such as subtype C, remains to be substantiated. In this study, we longitudinally characterized the evolution of the Env V1–V5 region from seven subtype C HIV-1 perinatally infected children with different clinical outcomes. We investigated the possible influence of viral genotype and humoral immune response on disease progression in infants.

Results: Genetic analyses revealed that rapid progressors (infants that died in the first …


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 Jan 2006

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 Jan 2006

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 …