Virology Commons^™

Antigenicity And Immunogenicity Of A Synthetic Human Immunodeficiency Virus Type 1 Group M Consensus Envelope Glycoprotein, Feng Gao, Eric A. Weaver, Zhongjing Lu, Yingying Li, Hua-Xin Liao, Benjiang Ma, S. Munir Alam, Richard M. Scearce, Laura L. Sutherland, Jae-Sung Yu, Julie M. Decker, George M. Shaw, David C. Montefiori, Bette T. Korber, Beatrice H. Hahn, Barton F. Haynes

Nebraska Center for Virology: Faculty Publications

Genetic variation of human immunodeficiency virus (HIV-1) represents a major obstacle for AIDS vaccine development. To decrease the genetic distances between candidate immunogens and field virus strains, we have designed and synthesized an artificial group M consensus env gene (CON6 gene) to be equidistant from contemporary HIV-1 subtypes and recombinants. This novel envelope gene expresses a glycoprotein that binds soluble CD4, utilizes CCR5 but not CXCR4 as a coreceptor, and mediates HIV-1 entry. Key linear, conformational, and glycan-dependent monoclonal antibody epitopes are preserved in CON6, and the glycoprotein is recognized equally well by sera from individuals infected with different HIV-1 …

Genome Of Deerpox Virus, C. L. Afonso, Gustavo A. Delhon, E. R. Tuhlman, Z. Lu, A. Zsak, V. M. Becerra, L. Zsak, G. F. Kutish, D. L. Rock

Nebraska Center for Virology: Faculty Publications

Deerpox virus (DPV), an uncharacterized and unclassified member of the Poxviridae, has been isolated from North American free-ranging mule deer (Odocoileus hemionus) exhibiting mucocutaneous disease. Here we report the genomic sequence and comparative analysis of two pathogenic DPV isolates, W-848-83 (W83) and W-1170-84 (W84). The W83 and W84 genomes are 166 and 170 kbp, containing 169 and 170 putative genes, respectively. Nucleotide identity between DPVs is 95% over the central 157 kbp. W83 and W84 share similar gene orders and code for similar replicative, structural, virulence, and host range functions. DPV open reading frames (ORFs) with putative …

Evolution Of Subtype C Hiv-1 Env In A Slowly Progressing Zambian Infant, Hong Zhang, Federico Hoffmann, Jun He, Xiang He, Chipepo Kankasa, Ruth Ruprecht, John T. West, Guillermo Orti, Charles Wood

Nebraska Center for Virology: Faculty Publications

Background: Given the high prevalence of mother to child infection, the development of a better understanding of African subtype C HIV-1 transmission and natural evolution is of significant importance. In this study, we genotypically and phenotypically characterized subtype C viruses isolated over a 67-month follow-up period from an in utero-infected Zambian infant. Changes in genotype and phenotype were correlated to alterations of the host humoral immune response.

Results: A comparison of baseline maternal and infant samples indicated that the infant sequences are monophyletic and contain a fraction of the diversity observed in the mother. This finding suggests that selective …

Epidemiological Characteristics Of Human Herpesvirus-8 Infection In A Large Population Of Antenatal Women In Zambia, W. Klaskala, B. P. Brayfield, C. Kankasa, G. Bhat, J. T. West, C. D. Mitchell, Charles Wood

Nebraska Center for Virology: Faculty Publications

Comprehensive data describing epidemiological characteristics of the human herpesvirus-8 or Kaposi’s sarcoma-associated herpesvirus (HHV-8 or KSHV) infection among pregnant women in a central sub-Saharan Africa are not available. This study determined virus prevalence estimates and the risk factors associated with HHV-8 infection. Cross-sectional, enrollment visit data were analyzed from a prospective cohort study of perinatal transmission of HHV-8 in Lusaka, Zambia. Exposure data were obtained via structured interview, physical examination, medical chart review, and laboratory testing. Among 3,160 antenatal women serologically screened for HHV-8 between September 1998 and October 2000, 40.2% were seropositive. The HHV-8 positive women were more likely …

Infectious Molecular Clone Of A Recently Transmitted Pediatric Human Immunodeficiency Virus Clade C Isolate From Africa: Evidence Of Intraclade Recombination, Ricky D. Grisson, Agnes-Laurence Chenine, Lan-Yu Yeh, Jun He, Charles Wood, Ganapati J. Bhat, Weidong Zu, Chipepo Kankasa, Ruth M. Ruprecht

Nebraska Center for Virology: Faculty Publications

Although human immunodeficiency virus type 1 (HIV-1) clade C continues to dominate the pandemic, only two infectious clade C proviral DNA clones have been described (N. Mochizuki, N. Otsuka, K. Matsuo, T. Shiino, A. Kojima, T. Kurata, K. Sakai, N. Yamamoto, S. Isomura, T. N. Dhole, Y. Takebe, M. Matsuda, and M. Tatsumi, AIDS Res. Hum. Retrovir. 15:1321–1324, 1999; T. Ndung’u, B. Renjifo, and M. Essex, J. Virol. 75:4964–4972, 2001). We have generated an infectious molecular clone of a pediatric clade C strain, HIV1084i, which was isolated from a Zambian infant infected either intrapartum or through breastfeeding. HIV1084i is an …

Interferon Regulatory Factor 7 Is Associated With Epstein-Barr Virus-Transformed Central Nervous System Lymphoma And Has Oncogenic Properties, Luwen Zhang, Jun Zhang, Que Lambert, Channing J. Der, Luis Del Valle, Judith Miklossy, Kamel Kahlili, You Zhou, Joseph S. Pagano

Nebraska Center for Virology: Faculty Publications

EBV transforms primary B cells, and the major EBV oncoprotein, latent membrane protein 1 (LMP-1), is required for the process. LMP-1 both induces the expression of IRF-7 and activates the IRF-7 protein by phosphorylation and nuclear translocation. Here we report that the expression of IRF-7 is increased in EBV-immortalized B lymphocytes compared with that in primary B cells. IRF-7 was phosphorylated and predominantly localized in the nucleus in the immortalized cells. The expression of IRF-7 was detected in 19 of 27 specimens of primary lymphomas of the human central nervous system by immunohistochemical analysis. The association between LMP-1 and IRF-7 …

The Latent Membrane Protein 1 Of Epstein-Barr Virus Establishes An Antiviral State Via Induction Of Interferon-Stimulated Genes, Jun Zhang, Subash C. Das, Catherine Kotalik, Asit K. Pattnaik, Luwen Zhang

Nebraska Center for Virology: Faculty Publications

Epstein-Barr virus (EBV) infection is associated with several 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. In this report, we show that LMP-1 is able to induce the expression of several interferon (IFN)-stimulated genes (ISGs) with antiviral properties such as 2’-5’ oligoadenylate synthetase (OAS), stimulated trans-acting factor of 50 kDa (STAF- 50), and ISG-15. LMP-1 inhibits vesicular stomatitis virus (VSV) replication at low multiplicity of infection (0.1 pfu/cell). The antiviral effect of LMP-1 is associated with the ability of LMP-1 …

Detection And Quantitation Of Bovine Respiratory Syncytial Virus Using Real-Time Quantitative Rt-Pcr And Quantitative Competitive Rt-Pcr Assays, Jenna Achenbaum, Christina L. Topliff, Ventzislav B. Vassilev, Ruben O. Donis, Kent M. Eskridge, Clayton L. Kelling

Nebraska Center for Virology: Faculty Publications

A single tube, fluorogenic probe-based, real-time quantitative reverse transcription-polymerase chain reaction (Q-RT-PCR) assay was developed for detection and quantitation of bovine respiratory syncytial virus (BRSV) using BioRad’s iCycler iQ™. Real-time Q-RT-PCR was compared with quantitative competitive RT-PCR (QC-RT-PCR) and viral titers. Viral mRNA levels were measured in BRSV-infected bovine turbinate cell lysate harvested at eight time points (1.5, 6, 12, 24, 36, 48, 60, 72 h) post-infection. A homologous BRSV cRNA standard was used for quantitation of the mRNA by plotting a standard curve of cycle threshold (Ct) values versus standard 10-fold dilutions of cRNA of known concentrations. Detection as …

Cd8+ T Cells Responding To Influenza Infection Reach And Persist At Higher Numbers Than Cd4+ T Cells Independently Of Precursor Frequency, Timothy J. Powell, Deborah M. Brown, Joseph A. Hollenbaugh, Tina Charbonneau, Roslyn A. Kemp, Susan L. Swain, Richard Dutton

Nebraska Center for Virology: Faculty Publications

The activation, localization, phenotypic changes, and function of CFSE-labeled naive influenza-specific CD8⁺ and CD4⁺ T cells following influenza infection were examined. Response of adoptively transferred CD8⁺ T cells was seen earliest in draining lymph node. Highly activated cells were found later in the lung, airways, and spleen, were cytolytic, and expressed IFN-γ upon restimulation. Similar amounts of division at early time points, but higher numbers of CD8⁺ T cells, were detected at 9 and 30 days postinfection after cotransfer of CD4⁺ and CD8⁺ T cells followed by infection. Transfer of much smaller numbers of …

Preserved Antigenicity Of Hiv-1 P24 Produced And Purified In High Yields From Plants Inoculated With A Tobacco Mosaic Virus (Tmv)-Derived Vector, D. M. Pérez-Filgueira, B. P. Brayfield, S. Phiri, M. V. Borca, Charles Wood, Thomas Jack Morris

Papers in Virology

Production of structural proteins from foot-and-mouth disease virus (FMDV) and bovine herpes virus (BHV-1) in Nicotiana benthamiana through the use of a tobacco mosaic virus-based vector (TMV-30B) has been reported previously. The development of the TMV-30B-HISc vector, a new version that adds a C-terminal histidine (His) sequence to the foreign protein expressed is described. Coding sequences from the FMDV VPl protein and the core protein, p24, from a clade C HIV-1 isolate from Zambia were cloned into the new vector and infective RNAs were generated for each construct to inoculate N. benthamiana plants. His-tagged proteins were purified from inoculated leaves …

In Vitro Expression Of Full-Length And Truncated Bovine Respiratory Syncytial Virus G Proteins And Their Antibody Responses In Balb/C Mice, Ryan P. Brady, Christina L. Topliff, Clayton L. Kelling

Nebraska Center for Virology: Faculty Publications

Bovine respiratory syncytial virus (BRSV) is a primary cause of lower respiratory tract disease in calves. Protection is incomplete following vaccination or natural infection, as re-infections are common. The objectives of this study were to create plasmid DNA constructs encoding the full-length, secreted, or conserved region of the BRSV G glycoprotein, and to compare and evaluate their expression in cell culture and potential to induce antibody responses in BALB/c mice. Transfection of COS-7 cells with plasmid DNA resulted in expression of the BRSV G region from each of the plasmid DNA constructs. Following inoculation of BALB/c mice with plasmid DNA, …

Heat Shock Protein 70 Protects Cells From Cell Cycle Arrest And Apoptosis Induced By Human Immunodeficiency Virus Type 1 Viral Protein R, Yuqi Zhao, Larisa Dubrovsky, Tatiana Iordanskaya, Mongzhong Chen, Dong Liang, Michael Bukrinsky, Sergey Iordanskiy

Nebraska Center for Virology: Faculty Publications

Viral protein R (Vpr) of human immunodeficiency virus type 1 (HIV-1) is an accessory protein that plays an important role in viral pathogenesis. This pathogenic activity of Vpr is related in part to its capacity to induce cell cycle G₂ arrest and apoptosis of target T cells. A screening for multicopy suppressors of these Vpr activities in fission yeast identified heat shock protein 70 (Hsp70) as a suppressor of Vpr-induced cell cycle arrest. Hsp70 is a member of a family of molecular chaperones involved in innate immunity and protection from environmental stress. In this report, we demonstrate that HIV-1 …

Prion Infection Of Skeletal Muscle Cells And Papillae In The Tongue, Ellyn R. Mulcahy, Jason C. Bartz, Anthony E. Kincaid, Richard Bessen

Nebraska Center for Virology: Faculty Publications

The presence of the prion agent in skeletal muscle is thought to be due to the infection of nerve fibers located within the muscle. We report here that the pathological isoform of the prion protein, PrP^Sc, accumulates within skeletal muscle cells, in addition to axons, in the tongue of hamsters following intralingual and intracerebral inoculation of the HY strain of the transmissible mink encephalopathy agent. Localization of PrP^Sc to the neuromuscular junction suggests that this synapse is a site for prion agent spread between motor axon terminals and muscle cells. Following intracerebral inoculation, the majority of PrP …

Cd4 T Cell Responses To Influenza Infection, Deborah M. Brown, Eulogia Roman, Susan L. Swain

Nebraska Center for Virology: Faculty Publications

Immune responses to viral infections involve a complex orchestration between innate signals and adaptive responses of specific T and B cells. Anti-viral CD4 cells can direct CD8 responses by secreting a Type 1 panel of cytokines including IFN-γ, IL-2 and TNF- α and can drive B cell production of IgG2a to neutralize infective viral particles. This review will focus specifically on the role of CD4 cells in the immune response to influenza, an acute, localized respiratory viral infection. We suggest that CD4 cells act as direct effectors in protection against influenza, may contribute to immunopathology and generate functionally distinct memory …

Distribution Of Kaposi Sarcoma–Associated Herpesvirus/Human Herpesvirus 8 In Maternal Saliva And Breast Milk In Zambia: Implications For Transmission, Brad P. Brayfield, Chipepo Kankasa, John T. West, Jubra Muyanga, Ganapati Bhat, Winslow Klaskala, Charles D. Mitchell, Charles Wood

Nebraska Center for Virology: Faculty Publications

Background. The seroprevalence of Kaposi sarcoma–associated herpesvirus (KSHV)/human herpesvirus 8 (HHV-8) in sub-Saharan Africa suggests that multiple routes of transmission exist. In the present study,we examined 2 possible routes of mother-to-child transmission, through breast milk and saliva, during the first 6 months after delivery. Methods. The prevalence of HHV-8 DNA in the breast-milk cells (n=75), milk supernatant (n=56), colostrum (n=2), and saliva cells (n=65) of HHV-8–seropositive mothers who recently gave birth was examined. Polymerase chain reaction analysis was performed for the detection of HHV-8 in cross-sectional samples isolated at 2, 4, and 6 months after delivery.

Results. None of the …

Multiple Signal Transducers And Activators Of Transcription Are Induced By Ebv Lmp-1, Luwen Zhang, Ke Hong, Jun Zhang, Joseph S. Pagano

Nebraska Center for Virology: Faculty Publications

Epstein-Barr virus (EBV) latent membrane protein 1 (LMP-1) is required for EBV immortalization of primary B cells in vitro. Signal transducers and activators of transcription (STATs) play a pivotal role in the initiation and maintenance of certain cancers. STAT proteins, especially STAT-1, -3, and -5, are persistently tyrosine phosphorylated or activated in many cancers. We show here that EBV-infected type III latency cells, in which the EBV oncoprotein, LMP-1 is expressed, express high levels of four STATs (STAT-1, -2, -3, and -5A) and that LMP-1 is responsible for the induction of three (STAT-1, -2, and -3). In addition, the C-terminal …

Phylogenetic Analyses Of Texas Isolates Indicate An Evolving Subtype Of The Clade B Feline Immunodeficiency Viruses, Eric A. Weaver, Ellen W. Collisson, Margaret Slater, Guan Zhu

Nebraska Center for Virology: Faculty Publications

Rigorous phylogenetic analyses were used to compare the nucleotide sequences of feline immunodeficiency virus strains isolated from Texas and throughout the world. The envelope V3-V4 sequences and capsid gene of the Texas isolates formed a cluster between subtypes B and E. Statistical comparisons with other published sequences confirmed that the Texas group is a unique cluster, possibly a new subtype, arising from subtype B.

Feline immunodeficiency virus (FIV) was initially isolated in 1987 from a cat in California with severe immunodeficiency and has been recognized as a common worldwide feline pathogen (11, 14, 19, 20, 33). FIV-infected cats exhibit a …

Cd46-Mediated Transduction Of A Species D Adenovirus Vaccine Improves Mucosal Vaccine Efficacy, Zenaido T. Camacho, Mallory A. Turner, Michael A. Barry, Eric A. Weaver

Nebraska Center for Virology: Faculty Publications

The high levels of preexisting immunity against Adenovirus type 5 (Ad5) have deemed Ad5 unusable for translation as a human vaccine vector. Low seroprevalent alternative viral vectors may be less impacted by preexisting immunity, but they may also have significantly different phenotypes from that of Ad5. In this study we compare species D Ads (26, 28, and 48) to the species C Ad5. In vitro transduction studies show striking differences between the species C and D viruses. Most notably, Ad26 transduced human dendritic cells much more effectively than Ad5. In vivo imaging studies showed strikingly different transgene expression profiles. The …

Phylogenetic Analyses Of Texas Isolates Indicate An Evolving Subtype Of The Clade B Feline Immunodeficiency Viruses, Eric A. Weaver, Ellen W. Collisson, Margaret Slater, Guan Zhu

Nebraska Center for Virology: Faculty Publications

Rigorous phylogenetic analyses were used to compare the nucleotide sequences of feline immunodeficiency virus strains isolated from Texas and throughout the world. The envelope V3-V4 sequences and capsid gene of the Texas isolates formed a cluster between subtypes B and E. Statistical comparisons with other published sequences confirmed that the Texas group is a unique cluster, possibly a new subtype, arising from subtype B.

Genomes Of The Parapoxviruses Orf Virus And Bovine Papular Stomatitis Virus, Gustavo A. Delhon, E. R. Tuhlman, C. L. Afonso, Z. Lu, A. De La Concha-Bermejillo, H. D. Lehmkuhl, M. E. Piccone, G. F. Kutish, D. L. Rock

Nebraska Center for Virology: Faculty Publications

Bovine papular stomatitis virus (BPSV) and orf virus (ORFV), members of the genus Parapoxvirus of the Poxviridae, are etiologic agents of worldwide diseases affecting cattle and small ruminants, respectively. Here we report the genomic sequences and comparative analysis of BPSV strain BV-AR02 and ORFV strains OV-SA00, isolated from a goat, and OV-IA82, isolated from a sheep. Parapoxvirus (PPV) BV-AR02, OV-SA00, and OV-IA82 genomes range in size from 134 to 139 kbp, with an average nucleotide composition of 64% G+C. BPSV and ORFV genomes contain 131 and 130 putative genes, respectively, and share colinearity over 127 genes, 88 of which …

Subpopulations Of Equine Infectious Anemia Virus Rev Coexist In Vivo And Differ In Phenotype, Prasith Baccam, Robert J. Thompson, Yuxing Li, Wendy O. Sparks, Michael Belshan, Karin S. Dorman, Yvonne Wannemuehler, J. Lindsay Oaks, James L. Cornette, Susan Carpenter

Nebraska Center for Virology: Faculty Publications

Lentiviruses exist in vivo as a population of related, nonidentical genotypes, commonly referred to as quasispecies. The quasispecies structure is characteristic of complex adaptive systems and contributes to the high rate of evolution in lentiviruses that confounds efforts to develop effective vaccines and antiviral therapies. Here, we describe analyses of genetic data from longitudinal studies of genetic variation in a lentivirus regulatory protein, Rev, over the course of disease in ponies experimentally infected with equine infectious anemia virus. As observed with other lentivirus data, the Rev variants exhibited a quasispecies character. Phylogenetic and partition analyses suggested that the Rev quasispecies …

Genome Of Bovine Herpesvirus 5, Gustavo A. Delhon, M. P. Moraes, Z. Lu, C. L. Afonso, E. F. Flores, R. Weiblen, G. F. Kutish, D. L. Rock

Nebraska Center for Virology: Faculty Publications

Here we present the complete genomic sequence of bovine herpesvirus 5 (BHV-5), an alphaherpesvirus responsible for fatal meningoencephalitis in cattle. The 138,390-bp genome encodes 70 putative proteins and resembles the α2 subgroup of herpesviruses in genomic organization and gene content. BHV-5 is very similar to BHV-1, the etiological agent of infectious bovine rhinotracheitis, as reflected by the high level of amino acid identity in their protein repertoires (average, 82%). The highest similarity to BHV-1 products (≥95% amino acid identity) is found in proteins involved in viral DNA replication and processing (UL5, UL15, UL29, and UL39) and in virion proteins (UL14, …

Bovine Herpes Virus Gd Protein Produced In Plants Using A Recombinant Tobacco Mosaic Virus (Tmv) Vector Possesses Authentic Antigenicity, D. M. Pérez Filgueira, P.I. Zamorano, M. G. Dominguez, O. Taboga, M. P. Del Medico Zajac, M. Puntel, S. A. Romera, Thomas Jack Morris, M. V. Borca, A. M. Sadir

Papers in Virology

A tobacco mosaic virus (TMV)-based vector was utilized for expression of a cytosolic form of the bovine herpesvirus type 1 (BHV-1) protein glycoprotein D (gDc). Nicotiana benthamiana plants were harvested 7 days after inoculation with RNA transcripts derived from the TMV-gDc recombinant virus. Recombinant gDc protein of expected electrophoretic mobility accumulated in inoculated leaves to a concentration of about 20 μg/g of fresh leaf tissue. Oil-based vaccines were formulated with crude foliar extracts to immunize mice parentally. After a single injection, animals developed a sustained and specific response to both the isolated gD and native virus particles. Cattle vaccinated with …

To The Editor: Reply To Sarmati, Brad P. Brayfield, John T. West, Charles D. Mitchell, Charles Wood

Nebraska Center for Virology: Faculty Publications

The letter by Sarmati et al. [1] presents data indicating that they were unable to find a significant correlation between human herpesvirus (HHV)–8 seropositivity and a history of spontaneous abortion in a group of 245 human immunodeficiency virus (HIV) type 1–seronegative women but that they did observe a correlation between high HHV-8 antibody titers (≥1:1280) and spontaneous abortion. Although it is possible that an increased risk of spontaneous abortion may be associated with active infection with HHV-8, at this point there is not enough evidence to support such an association. Given that several human herpes viruses are well-known agents of …

Identification Of The Nuclear Localization Signal Of Human Immunodeficiency Virus Type 2 Vpx, Michael Belshan, Lee Ratner

Nebraska Center for Virology: Faculty Publications

The Vpx protein of human immunodeficiency virus type 2 (HIV-2) is a viral accessory protein 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), Vpx is required for efficient virus replication in nondividing cells. Therefore, the localization of Vpx in cells is dynamic and dependent upon discrete domains of the protein. Expressed in the absence of other viral proteins, Vpx localizes to the nucleus of cells. However, if expressed with the Gag protein of HIV-2, Vpx localizes to the plasma membrane of cells. To …

Postnatal Human Herpesvirus 8 And Human Immunodeficiency Virus Type 1 Infection In Mothers And Infants From Zambia, Brad P. Brayfield, Saul Phiri, Chipepo Kankasa, Jubra Muyanga, Hamakwa Mantina, Geoffrey Kwenda, John T. West, Ganapati Bhat, Dave B. Marx, Winslow Klaskala, Charles D. Mitchell, Charles Wood

Nebraska Center for Virology: Faculty Publications

The specific route and timing of human herpesvirus (HHV) 8 infection in regions where Kaposi sarcoma is endemic are not known. HHV-8 infection and any risk factors that may be associated with HHV-8, including human immunodeficiency virus (HIV) type 1 infection, were monitored during the 12-month post-delivery period for 416 mothers and 485 infants from Lusaka, Zambia. HHV-8 incident infection rates during this period were 3.2 and 5.3 infections/100 person-years for infants and mothers, respectively. HHV-8 infection among infants was not associated with HHV-8 or HIV-1 infection in the mother. Among the HHV-8–positive infants, 2 of 12 tested were found …

Rapid Prion Neuroinvasion Following Tongue Infection, Jason C. Bartz, Anthony E. Kincaid, Richard A. Bessen

Nebraska Center for Virology: Faculty Publications

Food-borne transmission of prions can lead to infection of the gastrointestinal tract and neuroinvasion via the splanchnic and vagus nerves. Here we report that the transmission of transmissible mink encephalopathy (TME) is 100,000-fold more efficient by inoculation of prions into the tongues of hamsters than by oral ingestion. The incubation period following TME agent (hereinafter referred to as TME) inoculation into the lingual muscles was the shortest among the five nonneuronal routes of inoculation, including another intramuscular route. Deposition of the abnormal isoform of the prion protein, PrP^Sc, was first detected in the tongue and submandibular lymph node …

Epitope Mapping And Characterization Of A Novel Cd4-Induced Human Monoclonal Antibody Capable Of Neutralizing Primary Hiv-1 Strains, Shi-Hua Xiang, Liping Wang, Mariam Abreu, Chih-Chin Huang, Peter D. Kwong, Eric Rosenberg, James E. Robinson, Joseph Sodroski

Nebraska Center for Virology: Faculty Publications

Human immunodeficiency virus (HIV-1) enters target cells by binding its gp120 exterior envelope glycoprotein to CD4 and one of the chemokine receptors, CCR5 or CXCR4. CD4-induced (CD4i) antibodies bind gp120 more efficiently after CD4 binding and block the interaction with the chemokine receptor. Examples of CD4i antibodies are limited, and the prototypes of the CD4i antibodies exhibit only weak neutralizing activity against primary, clinical HIV-1 isolates. Here we report the identification of a novel antibody, E51, that exhibits CD4-induced binding to gp120 and neutralizes primary HIV-1 more efficiently than the prototypic CD4i antibodies. The E51 antibody blocks the interaction of …

Animal Anti-Apoptotic Genes Ameliorate The Loss Of Turgor In Water-Stressed Transgenic Tobacco, Tala Awada, D. D. Dunigan, M. B. Dickman

Nebraska Center for Virology: Faculty Publications

Nicotiana tabacum L. ‘Glurk’ plants were transformed with antiapoptotic animal genes [chicken Bcl-xl; nematode CED-9; chicken Bcl-xl(GA) a mutant of Bcl-xl; and a 3’ non-coding region of human Bcl-2, referred to as 161-1]. Our objectives were to determine whether plant transformation with anti-apoptotic genes ameliorates drought tolerance in tobacco plants by subjecting the plants to a dry-down period. The non-transformed Glurk and the transgenic Glurk harboring G115, which expresses β-glucuronidase, served as controls. Transformation of tobacco plants with animal anti-apoptotic genes significantly impacted the rates of photosynthesis (A) and stomatal conductance (g_s), but not to the same extent …

Identification Of Novel Domains Within Sox-2 And Sox-11 Involved In Autoinhibition Of Dna Binding And Partnership Specificity, Matthew S. Wiebe, Tamara K. Nowling, Angie Rizzino

Nebraska Center for Virology: Faculty Publications

Sox transcription factors play key regulatory roles throughout development, binding DNA through a consensus (A/T)(A/T)CAA(A/T)G sequence. Although many different Sox proteins bind to this se-quence, it has been observed that gene regulatory elements are commonly responsive to only a small subset of the entire family, implying that regulatory mechanisms exist to permit selective DNA bind-ing and/or transactivation by Sox family members. To identify and explore the mechanisms modu-lating gene activation by Sox proteins further, we compared the function of Sox-2 and Sox-11. This led to the discovery that Sox proteins are regulated differentially at multiple levels, including trans-activation, protein partnerships …