Genetics and Genomics Commons^™

Clade C Hiv-1 Isolates Circulating In Southern Africa Exhibit A Greater Frequency Of Dicysteine Motif-Containing Tat Variants Than Those In Southeast Asia And Cause Increased Neurovirulence, Vasudev R. Rao, Ujjwal Neogi, Joshua S, Talboom, Ligia Padilla, Mustafizur Rahman, Cari Fritz-French, Sandra Gonzalez-Ramirez, Anjali Verma, Charles Wood, Ruth M. Ruprecht, Udaykumar Ranga, Tasnim Azim, Vinayaka R. Prasad

Nebraska Center for Virology: Faculty Publications

Background: HIV-1 Clade C (Subtype C; HIV-1C) is responsible for greater than 50% of infections worldwide. Unlike clade B HIV-1 (Subtype B; HIV-1B), which is known to cause HIV associated dementia (HAD) in approximately 15% to 30% of the infected individuals, HIV-1C has been linked with lower prevalence of HAD (0 to 6%) in India and Ethiopia. However, recent studies report a higher prevalence of HAD in South Africa, Zambia and Botswana, where HIV-1C infections predominate. Therefore, we examined whether Southern African HIV-1C is genetically distinct and investigated its neurovirulence. HIV-1 Tat protein is a viral determinant of neurocognitive dysfunction. …

Global Neuroaids Roundtable, Jeymohan Joseph, Cristian L. Achim, Michael J. Boivin, Bruce J. Brew, David B. Clifford, Deborah A. Colosi, Ronald J. Ellis, Robert K. Heaton, Amadou Gallo-Diop, Igor Grant, Georgette D. Kanmogne, Mahendra Kumar, Scott Letendre, Thomas D. Marcotte, Avindra Nath, Carlos A. Pardo, Robert H. Paul, Lynn Pulliam, Kevin Robertson, Walter Royal Iii, Ned Sacktor, Pasiri Sithinamsuwan, Davey M. Smith, Victor Valcour, Brian Wigdahl, Charles Wood

Nebraska Center for Virology: Faculty Publications

In May 2012, the Division of AIDS Research at the National Institute of Mental Health (NIMH) organized the “Global NeuroAIDS Roundtable” in conjunction with the 11th International Symposium on Neurovirology and the 2012 Conference on HIV in the Nervous System. The meeting was held in New York, NY, USA and brought together NIMH-funded investigators who are currently working on projects related to the neurological complications of AIDS (NeuroAIDS) in Africa, Asia, Eastern Europe, and Latin America in order to provide an opportunity to share their recent findings and discuss the challenges encountered within each country. The major goals of the …

Towards Defining The Chloroviruses: A Genomic Journey Through A Genus Of Large Dna Viruses, Adrien Jeanniard, David D. Dunigan, James Gurnon, Irina V. Agarkova, Ming Kang, Jason Vitek, Garry Duncan, O William Mcclung, Megan Larsen, Jean-Michel Claverie, James L. Van Etten, Guillaume Blanc

Nebraska Center for Virology: Faculty Publications

Background: Giant viruses in the genus Chlorovirus (family Phycodnaviridae) infect eukaryotic green microalgae. The prototype member of the genus, Paramecium bursaria chlorella virus 1, was sequenced more than 15 years ago, and to date there are only 6 fully sequenced chloroviruses in public databases. Presented here are the draft genome sequences of 35 additional chloroviruses (287 – 348 Kb/319 – 381 predicted protein encoding genes) collected across the globe; they infect one of three different green algal species. These new data allowed us to analyze the genomic landscape of 41 chloroviruses, which revealed some remarkable features about these viruses. …

Evaluation Of Higher Plant Virus Resistance Genes In The Green Alga, Chlorella Variabilis Nc64a, During The Early Phase Of Infection With Paramecium Bursaria Chlorella Virus-1, Janet M. Rowe, David D. Dunigan, Guillaume Blanc, James R. Gurnon, Yuannan Xia, James L. Van Etten

Nebraska Center for Virology: Faculty Publications

With growing industrial interest in algae plus their critical roles in aquatic systems, the need to understand the effects of algal pathogens is increasing. We examined a model algal host–virus system, Chlorella variabilis NC64A and virus, PBCV-1. C. variabilis encodes 375 homologs to genes involved in RNA silencing and in response to virus infection in higher plants. Illumina RNA-Seq data showed that 325 of these homologs were expressed in healthy and early PBCV-1 infected (≤60 min) cells. For each of the RNA silencing genes to which homologs were found, mRNA transcripts were detected in healthy and infected cells. C. variabilis …

A Twin-Cysteine Motif In The V2 Region Of Gp120 Is Associated With Siv Envelope Trimer Stabilization, Christopher Bohl, Dane Bowder, Jesse Thompson, Levon Abrahamyan, Sandra Gonzalez-Ramirez, Youdong Mao, Joseph Sodroski, Charles Wood, Shi-Hua Xiang

Nebraska Center for Virology: Faculty Publications

The V1 and V2 variable regions of the primate immunodeficiency viruses contribute to the trimer association domain of the gp120 exterior envelope glycoprotein. A pair of V2 cysteine residues at 183 and 191 (‘‘twin cysteines’’) is present in several simian immunodeficiency viruses, human immunodeficiency virus type 2 (HIV-2) and some SIV_cpz lineages, but not in HIV-1. To examine the role of this potentially disulfide-bonded twin-cysteine motif, the cysteine residues in the SIVmac239 envelope glycoproteins were individually and pairwise substituted by alanine residues. All of the twin-cysteine mutants exhibited decreases in gp120 association with the Env trimer, membrane-fusing activity, and …

Hiv-1 Env C2-V4 Diversification In A Slow-Progressor Infant Reveals A Flat But Rugged Fitness Landscape, S. Abigail Smith, Charles Wood, John T. West

Nebraska Center for Virology: Faculty Publications

Human immunodeficiency virus type-1 (HIV-1) fitness has been associated with virus entry, a process mediated by the envelope glycoprotein (Env). We previously described Env genetic diversification in a Zambian, subtype C infected, slow-progressor child (1157i) in parallel with an evolving neutralizing antibody response. Because of the role the Variable-3 loop (V3) plays in transmission, cell tropism, neutralization sensitivity, and fitness, longitudinally isolated 1157i C2-V4 alleles were cloned into HIV-1_NL4-3-eGFP and -DsRed2 infectious molecular clones. The fluorescent reporters allowed for dual-infection competitions between all patient-derived C2-V4 chimeras to quantify the effect of V3 diversification and selection on fitness. ‘Winners’ …

‘‘Megavirales’’, A Proposed New Order For Eukaryotic Nucleocytoplasmic Large Dna Viruses, Philippe Colson, Xavier De Lamballerie, Natalya Yutin, Sassan Asgari, Yves Bigot, Dennis K. Bideshi, Xiao-Wen Cheng, Brian A. Federici, James L. Van Etten, Eugene V. Koonin, Bernard La Scola, Didier Raoult

Nebraska Center for Virology: Faculty Publications

The nucleocytoplasmic large DNA viruses (NCLDVs) comprise a monophyletic group of viruses that infect animals and diverse unicellular eukaryotes. The NCLDV group includes the families Poxviridae, Asfarviridae, Iridoviridae, Ascoviridae, Phycodnaviridae, Mimiviridae and the proposed family ‘‘Marseilleviridae’’. The family Mimiviridae includes the largest known viruses, with genomes in excess of one megabase, whereas the genome size in the other NCLDV families varies from 100 to 400 kilobase pairs. Most of the NCLDVs replicate in the cytoplasm of infected cells, within so-called virus factories. The NCLDVs share a common ancient origin, as demonstrated by evolutionary reconstructions that trace approximately 50 genes encoding …

Recent Advances On The Use Of Structural Biology For The Design Of Novel Envelope Immunogens Of Hiv-1, Shi-Hua Xiang

Nebraska Center for Virology: Faculty Publications

Many efforts have been made in the worldwide quest for a prophylactic HIV vaccine to end the AIDS pandemic, but none has yet succeeded. The lessons learned have repeatedly informed us that the traditional or conventional approaches directly using the pathogens or subunits will not be sufficient for an effective HIV/AIDS vaccine. Recent advances in structure-based technology have shown some promise in the quest for a better immunogen in HIV vaccine development. According to the basic binding structural relationship of an antigen and an antibody, structure-based antigen design could bring some hope for the development of an effective vaccine against …

The Highly Conserved Layer-3 Component Of The Hiv-1 Gp120 Inner Domain Is Critical For Cd4-Required Conformational Transitions, Anik Désormeaux, Mathieu Coutu, Halima Medjahed, Beatriz Pacheco, Alon Herschhorn, Christopher Gu, Shi-Hua Xiang, Youdong Mao, Joseph Sodroski, Andrés Finzi

Nebraska Center for Virology: Faculty Publications

The trimeric envelope glycoprotein (Env) of human immunodeficiency virus type 1 (HIV-1) mediates virus entry into host cells. CD4 engagement with the gp120 exterior envelope glycoprotein subunit represents the first step during HIV-1 entry. CD4-induced conformational changes in the gp120 inner domain involve three potentially flexible topological layers (layers 1, 2, and 3). Structural rearrangements between layer 1 and layer 2 have been shown to facilitate the transition of the envelope glycoprotein trimer from the unliganded to the CD4-bound state and to stabilize gp120-CD4 interaction. However, our understanding of CD4-induced conformational changes in the gp120 inner domain remains incomplete. Here, …

Analysis Of Primary Resistance Mutations To Hiv-1 Entry Inhibitors In Therapy Naive Subtype C Hiv-1 Infected Mother– Infant Pairs From Zambia, Hongyan Guo, Chang Liu, Bin Liu, Charles Wood, Xiaohong Kong

Nebraska Center for Virology: Faculty Publications

Background—Small molecular CCR5 inhibitors represent a new class of drugs for treating HIV-1 infection. The evaluation of the primary resistance mutations associated with entry inhibitors during HIV-1 perinatal transmission is required because they may have a profound impact on the clinical management in MTCT.

Objectives—To evaluate the primary resistance mutations to maraviroc and vicriviroc during perinatal transmission and analyze the sensitivity of Env derived from mother–infant pairs to maraviroc.

Study design—Nine MIPs infected by subtype C HIV-1 were recruited to analyze the prevalence and transmission of primary resistance mutations to maraviroc and vicriviroc. Moreover, Env derived from six MIPs were …

Early Childhood Infection Of Kaposi’S Sarcoma-Associated Herpesvirus In Zambian Households: A Molecular Analysis, Landon Olp, Danielle M. Shea, Maxine K. White, Clement Gondwe, Chipepo Kankasa, Charles Wood

Nebraska Center for Virology: Faculty Publications

Sub-Saharan Africa is endemic for Kaposi’s sarcoma-associated herpesvirus (KSHV) and there is a high rate of early childhood infection; however, the transmission sources are not well characterized. We examined household members as potential KSHV transmission sources to young children in the KSHV-endemic country of Zambia. To this end, we enrolled and followed Zambian households with at least one KSHV-seropositive child and collected longitudinal buccal swab samples. KSHV burden was evaluated and K1 sequences from the children were determined and analyzed for differences to K1 sequences from household members. The K1 sequences were also analyzed for evolution over time. We generated …

Inla Promotes Dissemination Of Listeria Monocytogenes To The Mesenteric Lymph Nodes During Food Borne Infection Of Mice, Elsa N. Bou Ghanem, Grant S. Jones, Tanya Myers-Morales, Pooja D. Patil, Achmad N. Hidayatullah, Sarah E. F. D'Orazio

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Intestinal Listeria monocytogenes infection is not efficient in mice and this has been attributed to a low affinity interaction between the bacterial surface protein InlA and E-cadherin on murine intestinal epithelial cells. Previous studies using either transgenic mice expressing human E-cadherin or mouse-adapted L. monocytogenes expressing a modified InlA protein (InlA(m)) with high affinity for murine E-cadherin showed increased efficiency of intragastric infection. However, the large inocula used in these studies disseminated to the spleen and liver rapidly, resulting in a lethal systemic infection that made it difficult to define the natural course of intestinal infection. We describe here a …

Multifactorial Patterns Of Gene Expression In Colonic Epithelial Cells Predict Disease Phenotypes In Experimental Colitis, Aubrey Leigh Frantz, Maria E. C. Bruno, Eric William Rogier, Halide Tuna, Donald A. Cohen, Subbarao Bondada, Ralph Lakshman Chelvarajan, J. Anthony Brandon, C. Darrell Jennings, Charlotte S. Kaetzel

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Background— The pathogenesis of inflammatory bowel disease (IBD) is complex and the need to identify molecular biomarkers is critical. Epithelial cells play a central role in maintaining intestinal homeostasis. We previously identified five “signature” biomarkers in colonic epithelial cells (CEC) that are predictive of disease phenotype in Crohn's disease. Here we investigate the ability of CEC biomarkers to define the mechanism and severity of intestinal inflammation.

Methods— We analyzed the expression of RelA, A20, pIgR, tumor necrosis factor (TNF), and macrophage inflammatory protein (MIP)-2 in CEC of mice with dextran sodium sulfate (DSS) acute colitis or T-cell-mediated chronic colitis. …

Escherichia Coli Recg Functionally Suppresses Human Bloom Syndrome Phenotypes, Michael W. Killen, Dawn M. Stults, William A. Wilson, Andrew J. Pierce

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Defects in the human BLM gene cause Bloom syndrome, notable for early development of tumors in a broad variety of tissues. On the basis of sequence similarity, BLM has been identified as one of the five human homologs of RecQ from Escherichia coli. Nevertheless, biochemical characterization of the BLM protein indicates far greater functional similarity to the E. coli RecG protein and there is no known RecG homolog in human cells. To explore the possibility that the shared biochemistries of BLM and RecG may represent an example of convergent evolution of cellular function where in humans BLM has evolved to …

Gene Expression Analysis Of A Murine Model With Pulmonary Vascular Remodeling Compared To End-Stage Ipah Lungs, Kayoko Shimodaira, Yoichiro Okubo, Eri Ochiai, Haruo Nakayama, Harutaka Katano, Megumi Wakayama, Minoru Shinozaki, Takao Ishiwatari, Daisuke Sasai, Naobumi Tochigi, Tetsuo Nemoto, Tsutomu Saji, Katsuhiko Kamei, Kazutoshi Shibuya

Microbiology, Immunology, and Molecular Genetics Faculty Publications

BACKGROUND: Idiopathic pulmonary arterial hypertension (IPAH) continues to be one of the most serious intractable diseases that might start with activation of several triggers representing the genetic susceptibility of a patient. To elucidate what essentially contributes to the onset and progression of IPAH, we investigated factors playing an important role in IPAH by searching discrepant or controversial expression patterns between our murine model and those previously published for human IPAH. We employed the mouse model, which induced muscularization of pulmonary artery leading to hypertension by repeated intratracheal injection of Stachybotrys chartarum, a member of nonpathogenic and ubiquitous fungus in our …

Characterization Of Species C Human Adenovirus Serotype 6 (Ad6), Eric A. Weaver, Reeti Khare, Mathew L. Hillestad, Donna Palmer, Philip Ng, Michael A. Barry

Nebraska Center for Virology: Faculty Publications

Adenovirus serotype (Ad5) is the most studied Ad. Ad1, 2, and 6 are also members of species C Ad and are presumed to have biologies similar to Ad5. In this work, we have compared the ability of Ad1, 2, 5, and 6 to infect liver and muscle after intravenous and intramuscular injection. We found that Ad6 was surprisingly the most potent at liver gene delivery and that Ad1 and Ad2 were markedly weaker than Ad5 and 6. To understand these differences, we sequenced the Ad6 genome. This revealed that the Ad6 fiber protein is surprisingly three shaft repeats shorter than …

Heme Oxygenase-1 Regulates The Immune Response To Influenza Virus Infection And Vaccination In Aged Mice, Nathan W. Cummins, Eric A. Weaver, Shannon M. May, Anthony J. Croatt, Oded Foreman, Richard B. Kennedy, Gregory A. Poland, Michael A. Barry, Karl A. Nath, Andrew D. Badley

Nebraska Center for Virology: Faculty Publications

Underlying mechanisms of individual variation in severity of influenza infection and response to vaccination are poorly understood. We investigated the effect of reduced heme oxygenase-1 (HO-1) expression on vaccine response and outcome of influenza infection. HO-1-deficient and wild-type (WT) mice (kingdom, Animalia; phylum, Chordata; genus/species, Mus musculus) were infected with influenza virus A/PR/8/34 with or without prior vaccination with an adenoviral-based influenza vaccine. A genome-wide association study evaluated the expression of single-nucleotide polymorphisms (SNPs) in the HO-1 gene and the response to influenza vaccination in healthy humans. HO-1-deficient mice had decreased survival after influenza infection compared to WT mice (median …

Cell-Free Circulating Mirna Biomarkers In Cancer., Meng-Hsuan Mo, Liang Chen, Yebo Fu, Wendy Wang, Sidney W. Fu

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Considerable attention and an enormous amount of resources have been dedicated to cancer biomarker discovery and validation. However, there are still a limited number of useful biomarkers available for clinical use. An ideal biomarker should be easily assayed with minimally invasive medical procedures but possess high sensitivity and specificity. Commonly used circulating biomarkers are proteins in serum, most of which require labor-intensive analysis hindered by low sensitivity in early tumor detection. Since the deregulation of microRNA (miRNA) is associated with cancer development and progression, profiling of circulating miRNAs has been used in a number of studies to identify novel minimally …

Triticum Mosaic Poacevirus Enlists P1 Rather Than Hc-Pro To Suppress Rna Silencing-Mediated Host Defense, Satyanarayana Tatineni, Feng Qu, Ruhui Li, Thomas Jack Morris, Roy French

Nebraska Center for Virology: Faculty Publications

Triticum mosaic virus (TriMV) is the type species of the newly established Poacevirus genus in the family Potyviridae. In this study, we demonstrate that in contrast to the helper component- proteinase (HC-Pro) of Potyvirus species, the P1 proteins of TriMV and Sugarcane steak mosaic poacevirus function in suppression of RNA silencing (SRS). TriMV P1 effectively suppressed silencing induced by single- or double-stranded RNAs (ss/ds RNAs), and disrupted the systemic spread of silencing signals at a step after silencing signal production. Interestingly, contrary to enhanced SRS activity of potyviral HC-Pro by co-expression with P1, the presence of TriMV HC-Pro reduced …

Identification Of Molecular Determinants From Moloney Leukemia Virus 10 Homolog (Mov10) Protein For Virion Packaging And Anti-Hiv-1 Activity, Aierken Abudu, Xiaojun Wang, Ying Dang, Tao Zhou, Shi-Hua Xiang, Yong -Hui Zheng

Nebraska Center for Virology: Faculty Publications

Background: MOV₁₀ inhibits HIV-1 replication after being packaged.

Results: A Gag binding plus all but one of seven helicase domains are required for MOV^₁₀ packaging. Nearly all residues are required for anti-HIV-1 activity. Conclusion: Gag binding is not sufficient for MOV₁₀ packaging, and multiple discontinuous domains regulate MOV₁₀ activity.

Significance: These findings uncover a new packaging mechanism and provide new insights into MOV₁₀ antiviral activity.

Contribution Of The Infection-Associated Complement Regulator-Acquiring Surface Protein 4 (Erpc) To Complement Resistance Of Borrelia Burgdorferi, Claudia Hammerschmidt, Teresia Hallström, Christine Skerka, Reinhard Wallich, Brian Stevenson, Peter F Zipfel, Peter Kraiczy

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Borrelia burgdorferi evades complement-mediated killing by interacting with complement regulators through distinct complement regulator-acquiring surface proteins (CRASPs). Here, we extend our analyses to the contribution of CRASP-4 in mediating complement resistance of B. burgdorferi and its interaction with human complement regulators. CRASP-4 (also known as ErpC) was immobilized onto magnetic beads and used to capture proteins from human serum. Following Western blotting, factor H (CFH), CFH-related protein 1 (CFHR1), CFHR2, and CFHR5 were identified as ligands of CRASP-4. To analyze the impact of native CRASP-4 on mediating survival of serum-sensitive cells in human serum, a B. garinii strain was generated …

Dynamics Of Envelope Evolution In Clade C Shiv-Infected Pig-Tailed Macaques During Disease Progression Analyzed By Ultra-Deep Pyrosequencing, For Yue Tso, Damien C. Tully, Sandra Gonzalez, Christopher Quince, On Ho, Patricia Polacino, Ruth M. Ruprecht, Shiu-Lok Hu, Charles Wood

Nebraska Center for Virology: Faculty Publications

Understanding the evolution of the human immunodeficiency virus type 1 (HIV-1) envelope during disease progression can provide tremendous insights for vaccine development, and simian-human immunodeficiency virus (SHIV) infection of nonhuman primate provides an ideal platform for such studies. A newly developed clade C SHIV, SHIV-1157ipd3N4, which was able to infect rhesus macaques, closely resembled primary HIV-1 in transmission and pathogenesis, was used to infect several pig-tailed macaques. One of the infected animals subsequently progressed to AIDS, whereas one remained a nonprogressor. The viral envelope evolution in the infected animals during disease progression was analyzed by a bioinformatics approach using ultra-deep …

Chloroviruses: Not Your Everyday Plant Virus, James L. Van Etten, David D. Dunigan

Nebraska Center for Virology: Faculty Publications

Viruses infecting higher plants are among the smallest viruses known and typically have four to ten protein-encoding genes. By contrast, many viruses that infect algae (classified in the virus family Phycodnaviridae) are among the largest viruses found to date and have up to 600 protein- encoding genes. This brief review focuses on one group of plaque-forming phycodnaviruses that infect unicellular chlorella-like green algae. The prototype chlorovirus PBCV-1 has more than 400 protein-encoding genes and 11 tRNA genes. About 40% of the PBCV-1 encoded proteins resemble proteins of known function including many that are completely unexpected for a virus. In many …

Molecular Genetic And Biochemical Characterization Of The Vaccinia Virus I3 Protein, The Replicative Single-Stranded Dna Binding Protein, Matthew D. Greseth, Kathleen A. Boyle, Matthew S. Bluma, Bethany Unger, Matthew S. Wiebe, Jamaria A. Soares-Martins, Nadi T. Wickramasekera, James Wahlberg, Paula Traktman

Nebraska Center for Virology: Faculty Publications

Vaccinia virus, the prototypic poxvirus, efficiently and faithfully replicates its approximately 200-kb DNA genome within the cytoplasm of infected cells. This intracellular localization dictates that vaccinia virus encodes most, if not all, of its own DNA replication machinery. Included in the repertoire of viral replication proteins is the I3 protein, which binds to single-stranded DNA (ssDNA) with great specificity and stability and has been presumed to be the replicative ssDNA binding protein (SSB). We substantiate here that I3 colocalizes with bromodeoxyuridine (BrdU)-labeled nascent viral genomes and that these genomes accumulate in cytoplasmic factories that are delimited by membranes derived from …

Lineage-Specific Differences Between Human And Simian Immunodeficiency Virus Regulation Of Gp120 Trimer Association And Cd4 Binding, Andrés Finzi, Beatriz Pacheco, Shi-Hua Xiang, Marie Pancera, Alon Herschhorn, Liping Wang, Xing Zeng, Anik Desormeaux, Peter D. Kwong, Joseph Sodroski

Nebraska Center for Virology: Faculty Publications

Metastable conformations of the gp120 and gp41 envelope glycoproteins of human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV) must be maintained in the unliganded state of the envelope glycoprotein trimer. Binding of gp120 to the primary receptor, CD4, triggers the transition to an open conformation of the trimer, promoting interaction with the CCR5 chemokine receptor and ultimately leading to gp41-mediated virus-cell membrane fusion and entry. Topological layers in the gp120 inner domain contribute to gp120-trimer association in the unliganded state and to CD4 binding. Here we describe similarities and differences between HIV-1 and SIVmac gp120. In both …

Subunit Organization Of The Membrane-Bound Hiv-1 Envelope Glycoprotein Trimer, Youdong Mao, Liping Wang, Christopher Gu, Alon Herschhorn, Shi-Hua Xiang, Hillel Haim, Xinzhen Yang, Joseph Sodroski

Nebraska Center for Virology: Faculty Publications

The trimeric human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) spike is a molecular machine that mediates virus entry into host cells and is the sole target for virus-neutralizing antibodies. The mature Env spike results from cleavage of a trimeric gp160 precursor into three gp120 and three gp41 subunits. Here we describe an ~11-Å cryo-EM structure of the trimeric HIV-1 Env precursor in its unliganded state. The three gp120 and three gp41 subunits form a cage-like structure with an interior void surrounding the trimer axis. Interprotomer contacts are limited to the gp41 transmembrane region, the torus-like gp41 ectodomain, and …

Comparative Analysis Of The Fusion Efficiency Elicited By The Envelope Glycoprotein V1–V5 Regions Derived From Human Immunodeficiency Virus Type 1 Transmitted Perinatally, Hongyan Guo, Levon Abrahamyan, Chang Liu, Mackenzie Waltke, Yunqi Geng, Qimin Chen, Charles Wood, Xiaohong Kong

Nebraska Center for Virology: Faculty Publications

Understanding the properties of viruses preferentially establishing infection during perinatal transmission of human immunodeficiency virus type 1 (HIV-1) is critical for the development of effective measures to prevent transmission. A previous study demonstrated that the newly transmitted viruses (in infants) of chronically infected mother–infant pairs (MIPs) were fitter in terms of growth, which was imparted by their envelope (Env) glycoprotein V1–V5 regions, than those in the corresponding chronically infected mothers. In order to investigate whether the higher fitness of transmitted viruses was conferred by their higher entry efficiency directed by the V1–V5 regions during perinatal transmission, the fusogenicity of Env …

Antibody Responses To Lytic And Latent Human Herpesvirus 8 Antigens Among Hiv-Infected Patients In Central China, Tiejun Zhang, Na He, Yingying Ding, Qingwu Jiang, Charles Wood

Nebraska Center for Virology: Faculty Publications

Human herpesvirus 8 (HHV8) is an important opportunistic infection of HIV/AIDS. However, very little is known about antibody seropositivities to HHV8 lytic and latent antigens among HIVinfected patients in China. Therefore, a cross-sectional study was conducted to explore HHV8 serostatus among 316 HIV-infected patients in a rural area of central China. The antibody seropositivity to HHV8 ORF65 (lytic) and LANA (latent) antigens was 12.7% and 10.4%, respectively. Patients who were naïve to antiretroviral therapy (ART) were more likely to be seropositive for antibodies to ORF65 (OR: 3.79; 95% CI: 1.71–8.42) and LANA (OR: 3.77; 95% CI: 1.55–9.14) than patients receiving …

Heme Oxygenase-1 Regulates The Immune Response To Influenza Virus Infection And Vaccination In Aged Mice, Nathan W. Cummins, Eric A. Weaver, Shannon M. May, Anthony J. Croatt, Oded Foreman, Richard B. Kennedy, Gregory A. Polan, Michael A. Barry, Karl A. Nath, Andrew D. Badley

Nebraska Center for Virology: Faculty Publications

Underlying mechanisms of individual variation in severity of influenza infection and response to vaccination are poorly understood. We investigated the effect of reduced heme oxygenase-1 (HO-1) expression on vaccine response and outcome of influenza infection. HO-1-deficient and wild-type (WT) mice (kingdom, Animalia; phylum, Chordata; genus/species, Mus musculus) were infected with influenza virus A/PR/8/34 with or without prior vaccination with an adenoviral-based influenza vaccine. A genome-wide association study evaluated the expression of single-nucleotide polymorphisms (SNPs) in the HO-1 gene and the response to influenza vaccination in healthy humans. HO-1-deficient mice had decreased survival after influenza infection compared to WT mice (median …

A Shared Gene Expression Signature In Mouse Models Of Ebv-Associated And Non-Ebv-Associated Burkitt Lymphoma, Kathryn T. Bieging, Kamonwan Fish, Subbarao Bondada, Richard Longnecker

Microbiology, Immunology, and Molecular Genetics Faculty Publications

The link between EBV infection and Burkitt lymphoma (BL) is strong, but the mechanism underlying that link has been elusive. We have developed a mouse model for EBV-associated BL in which LMP2A, an EBV latency protein, and MYC are expressed in B cells. Our model has demonstrated the ability of LMP2A to accelerate tumor onset, increase spleen size, and bypass p53 inactivation. Here we describe the results of total gene expression analysis of tumor and pretumor B cells from our transgenic mouse model. Although we see many phenotypic differences and changes in gene expression in pretumor B cells, the transcriptional …