Biological Phenomena, Cell Phenomena, and Immunity Commons^™

Kaposi Sarcoma-Associated Herpesvirus Degrades Cellular Toll-Interleukin-1 Receptor Domain-Containing Adaptor-Inducing Β-Interferon (Trif), Humera Ahmad, Rachel Gubbels, Florencia Meyer, Thomas Waterbury, Rongtuan Lin, Luwen Zhang

Nebraska Center for Virology: Faculty Publications

Kaposi sarcoma-associated herpesvirus (KSHV) is a human ƴ - herpesvirus associated with several human malignancies. The replication and transcription activator (RTA) is necessary and sufficient for the switch from KSHV latency to lytic replication. Toll-interleukin-1 receptor (TIR) domain-containing adaptorinducing β-interferon (TRIF, also called TIR-domain-containing adaptor molecule-1 (TICAM-1)) is a signaling adaptor molecule that is critically involved in the Toll-like receptor 3 (TLR-3) and TLR-4 signaling pathways for type I interferon (IFN) production, a key component of innate immunity against microbial infection. In this report, we find a new mechanism by which RTA blocks innate immunity by targeting cellular TRIF. RTA …

Robust Rnai-Based Resistance To Mixed Infection Of Three Viruses In Soybean Plants Expressing Separate Short Hairpins From A Single Transgene, Xiuchun Zhang, Shirley Sato, Xiaohong Ye, Anne E. Dorrance, Thomas Jack Morris, Thomas E. Clemente, Feng Qu

Nebraska Center for Virology: Faculty Publications

Transgenic plants expressing double-stranded RNA (dsRNA) of virus

origin have been previously shown to confer resistance to virus infections

through the highly conserved RNA-targeting process termed RNA silencing

or RNA interference (RNAi). In this study we applied this strategy to

soybean plants and achieved robust resistance to multiple viruses with a

single dsRNA-expressing transgene. Unlike previous reports that relied

on the expression of one long inverted repeat (IR) combining sequences

of several viruses, our improved strategy utilized a transgene designed to

express several shorter IRs. Each of these short IRs contains highly conserved

sequences of one virus, forming dsRNA of …

Critical Role Of Leucine-Valine Change In Distinct Low Ph Requirements For Membrane Fusion Between Two Related Retrovirus Envelopes, Marceline Côté, Yi-Min Zheng, Kun Li, Shi-Hua Xiang, Lorraine M. Albritton, Shan-Lu Liu

Nebraska Center for Virology: Faculty Publications

Many viruses use a pH-dependent pathway for fusion with host cell membrane, the mechanism of which is still poorly understood. Here we report that a subtle leucine (Leu)-valine (Val) change at position 501 in the envelope glycoproteins (Envs) of two related retroviruses, jaagsiekte sheep retro-virus (JSRV) and enzootic nasal tumor virus (ENTV), is responsible for their distinct low pH requirements for membrane fusion and infection. The Leu and Val residues are predicted to reside within the C-terminal heptad repeat (HR2) region of JSRV and ENTV Envs, particularly proximal to the hairpin turn of the putative six-helix bundle (6HB). Substitution of …

Hiv-1 Clade B And C Isolates Exhibit Differential Replication: Relevance To Macrophage-Mediated Neurotoxicity, Agnes A. Constantino, Yunlong Huang, Hong Zhang, Charles Wood, Jialin C. Zheng

Nebraska Center for Virology: Faculty Publications

HIV-associated neurocognitive disorders (HAND) continue to be a consequence of HIV-1 infection among clade B-infected individuals. In contrast, the incidence of severe neurological impairment is lower among clade C-infected patients in regions of Sub-Saharan Africa and India. Biological aspects such as replication, cytopathicity, inflammatory response, and neurotoxicity unique to each clade influence neuropathogenicity and ultimately affect the clinical outcome of the disease. We hypothesize that productive infection by clade C isolates leads to macrophagemediated neurotoxicity, although to a lesser extent than clade B isolates. Using a panel of primary isolates of clades B and C we demonstrated that clade B …

Hiv-1 Effects On Neuropsychological Performance In A Resource-Limited Country, Zambia, Gabriel Holguin, Mwanza Banda, Elizabeth J. Willen, Costantine Malama, Kaseya O. Chiyenu, Victor C. Mudenda, Charles Wood

Nebraska Center for Virology: Faculty Publications

Zambia has substantially been affected by the HIV/AIDS epidemic with prevalence rates at 14% in a population estimated at 12 million. Yet, the extent of HIV-associated neurocognitive disorders (HAND) in this population remains to be clearly understood. A series of culturally appropriate neuropsychological (NP) assessments [International HIV Dementia Scale (IHDS), Color Trails Test 1 and 2, Grooved pegboard Test, and Time Gait Test] were used to test the effects of HIV on NP performance of HIV seropositive and seronegative individuals. Twenty-two percent HIV positive individuals ARV naïve met the criteria for IHDS-defined NP impairment. Gender significantly influenced the performance on …

The Zambia Children's Ks-Hhv8 Study: Rationale, Study Design, And Study Methods, Veenu Minhas, Kay L. Crabtree, Ann Chao, Janet M. Wojcicki, Adrian M. Sifuniso, Catherine Nkonde, Chipepo Kankasa, Charles D. Mitchell, Charles Wood

Nebraska Center for Virology: Faculty Publications

The epidemic of human immunodeficiency virus in Zambia has led to a dramatic rise in the incidence of human herpesvirus-8 (HHV-8)–associated Kaposi's sarcoma in both adults and children. However, there is a paucity of knowledge about the routes of HHV-8 transmission to young children. The Zambia Children's KS-HHV8 Study, a large, prospective cohort study in Lusaka, Zambia, was launched in 2004 to investigate the role of household members as a source of HHV-8 infection in young children and social behaviors that may modify the risk of HHV-8 acquisition. This cohort is distinct from other epidemiologic studies designed to investigate HHV-8 …

Prevalence Of Human Herpesvirus 8 (Hhv8) And Hepatitis C Virus (Hcv) In A Rural Community With High Risk For Blood Borne Infections In Central China, Tiejun Zhang, Na He, Yingying Ding, Kay L. Crabtree, Veenu Minhas, Charles Wood

Nebraska Center for Virology: Faculty Publications

Former illegal blood donation in the past decade has caused HIV outbreaks in some rural areas in China. Other HIV associated virus infections, such as human herpesvirus 8 (HHV8) in such areas are still not well defined. In order to explore HHV8 and HCV seroprevalence and potential risk factors in such areas, a cross-sectional study with 305 HIV positive and 315 HIV negative subjects recruited from a rural county in Shanxi province was conducted, where illegal blood collection was reported. Interview questionnaires and serum testing were carried out with these participants. HCV and HHV8 seroprevalence were found to be higher …

Comparison Of Adenoviruses As Oncolytics And Cancer Vaccines In An Immunocompetent B Cell Lymphoma Model, Eric A. Weaver, Christopher Y. Chen, Shannon M. May, Mary E. Barry, Michael A. Barry

Nebraska Center for Virology: Faculty Publications

We have screened human adenoviruses (Ads) for oncolytic activity against a variety of mouse and hamster cell lines and have found a number that are susceptible to a variety of Ad serotypes. A20 lymphoma is derived from BALB/c mice and is susceptible to infection and killing by a variety of human Ads. A20 is also a suitable cancer vaccine model, because these cells express a unique immunoglobulin variable region that can be targeted by vaccination. To compare Ads as cancer vaccines versus Ads as oncolytics, A20 tumors were initiated in im- munocompetent BALB/c mice. Mice immunized with first-generation Ad5 expressing …

Species D Adenoviruses As Oncolytics Against B-Cell Cancers, Christopher Y. Chen, Julien S. Senac, Eric A. Weaver, Shannon M. May, Diane F. Jelinek, Philip Greipp, Thomas Witzig, Michael A. Barry

Nebraska Center for Virology: Faculty Publications

Purpose: Oncolytic viruses are self-amplifying anticancer agents that make use of the natural ability of viruses to kill cells. Adenovirus serotype 5 (Ad5) has been extensively tested against solid cancers, but less so against B-cell cancers because these cells do not generally express the coxsackie and adenoviral receptor (CAR). To determine whether other adenoviruses might have better potency, we "mined" the adenovirus virome of 55 serotypes for viruses that could kill B-cell cancers.

Experimental Design: Fifteen adenoviruses selected to represent Ad species B, C, D, E, and F were tested in vitro against cell lines and primary patient B-cell cancers …

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 …

Generation Of A Kupffer Cell-Evading Adenovirus For Systemic And Liver-Directed Gene Transfer, Reeti Khare, Shannon M. May, Francesco Vetrini, Eric A. Weaver, Donna Palmer, Amanda Rosewell, Nathan Grove, Philip Ng, Michael A. Barry

Nebraska Center for Virology: Faculty Publications

As much as 90% of an intravenously (i.v.) injected dose of adenovirus serotype 5 (Ad5) is absorbed and destroyed by liver Kupffer cells. Viruses that escape these cells can then transduce hepatocytes after binding factor X (FX). Given that interactions with FX and Kupffer cells are thought to occur on the Ad5 hexon protein, we replaced its exposed hypervariable regions (HVR) with those from Ad6. When tested in vivo in BALB/c mice and in hamsters, the Ad5/6 chimera mediated >10 times higher transduction in the liver. This effect was not due to changes in FX binding. Rather, Ad5/6 appeared to …

Banf1 Is Required To Maintain The Self-Renewal Of Both Mouse And Human Embryonic Stem Cells, Jesse L. Cox, Sunil K. Mallanna, Briana D. Ormsbee, Michelle Desler, Matthew S. Wiebe, Angie Rizzino

Nebraska Center for Virology: Faculty Publications

Self-renewal is a complex biological process necessary for maintaining the pluripotency of embryonic stem cells (ESCs). Recent studies have used global proteomic techniques to identify proteins that associate with the master regulators Oct4, Nanog, and Sox2 in ESCs or in ESCs during the early stages of differentiation. Through an unbiased proteomic screen, Banf1 was identified as a Sox2- associated protein. Banf1 has been shown to be essential for worm and fly development but, until now, its role in mammalian development and ESCs has not been explored. In this study, we examined the effect of knocking down Banf1 on ESCs. We …

Human Papillomavirus 16 Variants From Zambian Women With Normal Pap Smears, Yan Jun Lei, Kgomotso Makhaola, Daraporn Pittayakhajonwut, Charles Wood, Peter C. Angeletti

Nebraska Center for Virology: Faculty Publications

Human papillomavirus (HPV) type 16 is the most prevalent high-risk viral genotype associated with cervical cancer. Six distinct phylogenetic clusters of HPVs have been identified and are distributed differently across five continents. HPV16 DNA was extracted from cervico-lavage samples from women with normal pap smears. The LCR regions were amplified in triplicate, cloned, sequenced, and analyzed from a total of 11 recovered HPV16 positive samples [Ng’andwe et al. (2007): BMC Infect Dis 7:77] were analyzed for sequence variation. The HPV16 LCR variants were assessed for promoter activity by use of a luciferase reporter gene. Six novel HPV16 variants with nucleotide …

Advances And Future Challenges In Adenoviral Vector Pharmacology And Targeting, Reeti Khare, Christopher Y. Chen, Eric A. Weaver, Michael A. Barry

Nebraska Center for Virology: Faculty Publications

Adenovirus is a robust vector for therapeutic applications, but its use is limited by our understanding of its complex in vivo pharmacology. In this review we describe the necessity of identifying its natural, widespread, and multi-faceted interactions with the host since this information will be crucial for efficiently redirecting virus into target cells. In the rational design of vectors, the notion of overcoming a sequence of viral “sinks” must be combined with re-targeting to target populations with capsid as well as shielding the vectors from pre-existing or toxic immune responses. It must also be noted that most known adenoviral pharmacology …

Tca Cycle Inactivation In Staphylococcus Aureus Alters Nitric Oxide Production In Raw 264.7 Cells, Chandirasegaran Massilamany, Arunakumar Gangaplara, Donald J. Gardner, James M. Musser, David J. Steffen, Greg A. Somerville, Jay Reddy

Jay Reddy Publications

Inactivation of the Staphylococcus aureus tricarboxylic acid (TCA) cycle delays the resolution of cutaneous ulcers in a mouse soft tissue infection model. In this study, it was observed that cutaneous lesions in mice infected with wild-type or isogenic aconitase mutant S. aureus strains contained comparable inflammatory infiltrates, suggesting the delayed resolution was independent of the recruitment of immune cells. These observations led us to hypothesize that staphylococcal metabolism can modulate the host immune response. Using an in vitro model system involving RAW 264.7 cells, the authors observed that cells cultured with S. aureus aconitase mutant strains produced significantly lower amounts …

Mir-27b*, An Oxidative Stress-Responsive Microrna Modulates Nuclear Factor-Kb Pathway In Raw 264.7 Cells, Sivasubramani Thulasingam, Chandirasegaran Massilamany, Arunakumar Gangaplara, Hongjiu Dai, Shahlo Yarbaeva, Sakthivel Subramaniam, Jean-Jack Riethoven, James Eudy, Marjorie F. Lou, Jay Reddy

Jay Reddy Publications

Reactive oxygen species (ROS) produced in macrophages is critical for microbial killing, but they also take part in inflammation and antigen presentation functions. MicroRNAs (miRNAs) are endogenous regulators of gene expression, and they can control immune responses. To dissect the complex nature of ROS-mediated effects in macrophages, we sought to characterize miRNAs that are responsive to oxidative stress-induced with hydrogen peroxide (H₂O₂) in the mouse macrophage cell line, RAW 264.7. We have identified a set of unique miRNAs that are differentially expressed in response to H₂O₂. These include miR-27a*, miR-27b*, miR-29b*, miR-24-2*, …

Identification Of A Second Mimicry Epitope From Acanthamoeba Castellanii That Induces Cns Autoimmunity By Generating Cross-Reactive T Cells For Mbp 89–101 In Sjl Mice, Chandirasegaran Massilamany, Oluwatoyin A. Asojo, Arunakumar Gangaplara, David J. Steffen, Jay Reddy

Jay Reddy Publications

We had previously reported that Acanthamoeba castellanii (ACA) contains a mimicry epitope for proteolipid protein 139–151 capable of inducing central nervous system (CNS) autoimmunity in SJL/J mice. We now present evidence that ACA also contains a mimicry epitope for myelin basic protein (MBP) 89–101, a derivative from amoebic nicotinamide adenine dinucleotide dehydrogenase subunit 2 (NAD). The epitope, NAD 108–120, contains a discontinuous stretch of six amino acids in the core region (VVFFKNIILIGFL) sharing 46% identity with MBP 89–101 (VHFFKNIVTPRTP; identical residues are underlined). SJL mice immunized with NAD 108–120 develop encephalomyelitis similar to the disease induced by the cognate peptide. …

An Epitope From Acanthamoeba Castellanii That Cross-React With Proteolipid Protein 139-151-Reactive T Cells Induces Autoimmune Encephalomyelitis In Sjl Mice, Chandirasegaran Massilamany, David Steffan, Jay Reddy

Jay Reddy Publications

We report here that an epitope (aa, 83-95) derived from Acanthamoeba castellanii (ACA) induces clinical signs of experimental autoimmune encephalomyelitis (EAE) in SJL/J mice reminiscent of the disease induced with myelin proteolipid protein (PLP) 139-151. By using IA^s/tetramers, we demonstrate that both ACA 83-95 and PLP 139-151 generate antigen-specific cross-reactive CD4 T cells and the T cells secrete identical patterns of cytokines and induce EAE with a similar severity. These results may provide insights into the pathogenesis of multiple sclerosis and ACA-induced granulomatous encephalitis.

Neuroaids In Africa, Kevin Robertson, Jeff Liner, James Hakim, Jean-Louis Sankalé, Igor Grant, Scott Letendre, David Clifford, Amadou Gallo Diop, Assan Jaye, Georgette Kanmogne, Alfred Njamnshi, T. Dianne Langford, Tufa Gemechu Weyessa, Charles Wood, Mwanza Banda, Mina Hosseinipour, Ned Sacktor, Noeline Nakasuja, Paul Bangirana, Robert Paul, John Joska, Joseph Wong, Michael Boivin, Penny Holding, Betsy Kammerer, Annelies Van Rie, Prudence Ive, Avindra Nath, Kathy Lawler, Clement Adebamowo, Walter Royal Iii, Jeymohan Joseph

Nebraska Center for Virology: Faculty Publications

In July 2009, the Center for Mental Health Research on AIDS at the National Institute of Mental Health organized and supported the meeting “NeuroAIDS in Africa.” This meeting was held in Cape Town, South Africa, and was affiliated with the 5th IAS Conference on HIV Pathogenesis, Treatment and Prevention. Presentations began with an overview of the epidemiology of HIV in sub-Saharan Africa, the molecular epidemiology of HIV, HIV-associated neurocognitive disorders (HANDs), and HAND treatment. These introductory talks were followed by presentations on HAND research and clinical care in Botswana, Cameroon, Ethiopia, The Gambia, Kenya, Malawi, Nigeria, Senegal, South Africa, Uganda, …

Functional Properties Of The Hiv-1 Subtype C Envelope Glycoprotein Associated With Mother-To-Child Transmission, Hong Zhang, Marzena Rola, John T. West, Damien C. Tully, Piotr Kubis, Jun He, Chipepo Kankasa, Charles Wood

Nebraska Center for Virology: Faculty Publications

Understanding the properties of viruses capable of establishing infection during perinatal transmission of HIV-1 is critical for designing effective means of limiting transmission. We previously demonstrated that the newly transmitted viruses (in infant) were more fit in growth, as imparted by their envelope glycoproteins, than those in their corresponding mothers. Here, we further characterized the viral envelope glycoproteins from six mother-infant transmission pairs and determined whether any specific envelope functions correlate with HIV-1 subtype C perinatal transmission. We found that most newly transmitted viruses were less susceptible to neutralization by their maternal plasma compared to contemporaneous maternal viruses. However, the …

Chronology And Evolution Of The Hiv-1 Subtype C Epidemic In Ethiopia, Damien C. Tully, Charles Wood

Nebraska Center for Virology: Faculty Publications

Objective—To reconstruct the onset date and evolutionary history of the HIV-1 subtype C epidemic in Ethiopia - one of the earliest recorded subtype C epidemics in the world.

Design—HIV-1 C env sequences with a known sampling year isolated from HIV-1 positive patients from Ethiopia between 1984 and 2003.

Methods—Evolutionary parameters including origin and demographic growth patterns were estimated using a Bayesian coalescent-based approach under either strict or relaxed molecular clock models.

Results—Bayesian evolutionary analysis indicated a most recent common ancestor date of 1965 with three distinct epidemic growth phases. Regression analysis of root-to-tip distances revealed a highly similar estimate for …

Enhancement Of Autophagy During Lytic Replication By The Kaposi’S Sarcoma-Associated Herpesvirus Replication And Transcription Activator, Hui-Ju Wen, Zhilong Yang, You Zhou, Charles Wood

Nebraska Center for Virology: Faculty Publications

Autophagy is one of two major degradation systems in eukaryotic cells. The degradation mechanism of autophagy is required to maintain the balance between the biosynthetic and catabolic processes and also contributes to defense against invading pathogens. Recent studies suggest that a number of viruses can evade or subvert the host cell autophagic pathway to enhance their own replication. Here, we investigated the effect of autophagy on the KSHV (Kaposi’s sarcoma-associated herpesvirus) life cycle. We found that the inhibition of autophagy reduces KSHV lytic reactivation from latency, and an enhancement of autophagy can be detected during KSHV lytic replication. In addition, …

Chlorella Viruses Encode Most, If Not All, Of The Machinery To Glycosylate Their Glycoproteins Independent Of The Endoplasmic Reticulum And Golgi, James L. Van Etten, James Gurnon, Giane M. Yanai-Balser, David Dunigan, Michael V. Graves

Nebraska Center for Virology: Faculty Publications

In contrast to all other viruses that use the host machinery located in the endoplasmic reticulum and Golgi to glycosylate their glycoproteins, the large dsDNA-containing chlorella viruses encode most, if not all, of the components to glycosylate their major capsid proteins. Furthermore, all experimental results indicate that glycosylation occurs independent of the endoplasmic reticulum and Golgi. (Review article)

Protection Against Mucosal Shiv Challenge By Peptide And Helper-Dependent Adenovirus Vaccines, Eric A. Weaver, Pramod N. Nehete, Bharti P. Nehete, Stephanie J. Buchl, Donna Palmer, David C. Montefiori, Philip Ng, K. Jagannadha Sastry, Michael A. Barry

Nebraska Center for Virology: Faculty Publications

Groups of rhesus macaques that had previously been immunized with HIV-1 envelope (env) peptides and first generation adenovirus serotype 5 (FG-Ad5) vaccines expressing the same peptides were immunized intramuscularly three times with helperdependent adenovirus (HD-Ad) vaccines expressing only the HIV-1 envelope from JRFL. No gag, pol, or other SHIV genes were used for vaccination. One group of the FG-Ad5- immune animals was immunized three times with HD-Ad5 expressing env. One group was immunized by serotype-switching with HD-Ad6, HD-Ad1, and HD-Ad2 expressing env. Previous work demonstrated that serum antibody levels against env were significantly higher in the serotype-switched group than in …

Comparison Of Replication-Competent, First Generation, And Helper-Dependent Adenoviral Vaccines, Eric A. Weaver, Pramod N. Nehete, Stephanie S. Buchl, Julien S. Senac, Donna Palmer, Philip Ng, K. Jagannadha Sastry, Michael A. Barry

Nebraska Center for Virology: Faculty Publications

All studies using human serotype 5 Adenovirus (Ad) vectors must address two major obstacles: safety and the presence of pre-existing neutralizing antibodies. Helper-Dependent (HD) Ads have been proposed as alternative vectors for gene therapy and vaccine development because they have an improved safety profile. To evaluate the potential of HD-Ad vaccines, we compared replication-competent (RC), first-generation (FG) and HD vectors for their ability to induce immune responses in mice. We show that RC-Ad5 and HD-Ad5 vectors generate stronger immune responses than FG-Ad5 vectors. HD-Ad5 vectors gave lower side effects than RC or FG-Ad, producing lower levels of tissue damage and …

Human Ubc9 Contributes To Production Of Fully Infectious Human Immunodeficiency Virus Type 1 Virions, Tareq Jaber, Christopher R. Bohl, Gentry L. Lewis, Charles Wood, John T. West Jr., Robert A. Weldon Jr.

Nebraska Center for Virology: Faculty Publications

Ubc9 was identified as a cellular protein that interacts with the Gag protein of Mason-Pfizer monkey virus. We show here that Ubc9 also interacts with the human immunodeficiency virus type 1 (HIV-1) Gag protein and that their interaction is important for virus replication. Gag was found to colocalize with Ubc9 predominantly at perinuclear puncta. While cells in which Ubc9 expression was suppressed with RNA interference produced normal numbers of virions, these particles were 8- to 10-fold less infectious than those produced in the presence of Ubc9. The nature of this defect was assayed for dependence on Ubc9 during viral assembly, …

Human Papillomavirus 16 E5 Induces Bi-Nucleated Cell Formation By Cell-Cell Fusion, Lulin Ha, Kendra Plafker, Valeriya Vorozhoko, Rosemary E. Zuna, Marie H. Hanigan, Gary J. Gorbsky, Scott M. Plafker, Peter C. Angeletti, Brian P. Ceresa

Nebraska Center for Virology: Faculty Publications

Human Papillomaviruses (HPV) 16 is a DNA virus encoding three oncogenes – E5, E6, and E7. The E6 and E7 proteins have well-established roles as inhibitors of tumor suppression, but the contribution of E5 to malignant transformation is controversial. Using spontaneously immortalized human keratinocytes (HaCaT cells), we demonstrate that expression of HPV16 E5 is necessary and sufficient for the formation of bi-nucleated cells, a common characteristic of precancerous cervical lesions. Expression of E5 from non-carcinogenic HPV6b does not produce bi-nucleate cells. Video microscopy and biochemical analyses reveal that bi-nucleates arise through cell-cell fusion. Although most E5-induced bi-nucleates fail to propagate, …

X4 Human Immunodeficiency Virus Type 1 Gp120 Down-Modulates Expression And Immunogenicity Of Codelivered Antigens, Avi-Hai Hovav, Michael Santosuosso, Maytal Bivas-Benita, Andre Plair, Alex Cheng, Mazal Elnekave, Elda Righi, Tao Chen, Satoshi Kashiwagi, Michael W. Panas, Shi-Hua Xiang, Karina Furmanov, Norman L. Letvin, Mark C. Poznansky

Nebraska Center for Virology: Faculty Publications

In order to increase the immune breadth of human immunodeficiency virus (HIV) vaccines, strategies such

as immunization with several HIV antigens or centralized immunogens have been examined. HIV-1 gp120

protein is a major immunogen of HIV and has been routinely considered for inclusion in both present and

future AIDS vaccines. However, recent studies proposed that gp120 interferes with the generation of immune

response to codelivered antigens. Here, we investigate whether coimmunization with plasmid-encoded gp120

alters the immune response to other coadministered plasmid encoded antigens such as luciferase or ovalbumin

in a mouse model. We found that the presence of gp120 …

A Comparative Study Of Hiv-1 Clade C Env Evolution In A Zambian Infant With An Infected Rhesus Macaque During Disease Progression, For Yue Tso, Federico G. Hoffmann, Damien C. Tully, Philippe Lemey, Robert A. Rasmussen, Hong Zhang, Ruth M. Ruprecht, Charles Wood

Nebraska Center for Virology: Faculty Publications

Objective—To evaluate whether HIV-1 clade C (HIV-C) envelope variations that arise during disease progression in rhesus macaque model reflect changes that occur naturally in human infection.

Design—An infant macaque was infected with SHIV-1157i, an R5 tropic clade C SHIV (SHIV-C) which expresses a primary HIV-C envelope derived from an infected human infant, and monitored over a five-year period. Genetic variation of the V1-V5 envelope region, which is the main target for humoral immune responses, derived from the infected macaque and infant was examined.

Methods—V1-V5 envelope region were cloned and sequenced from longitudinal PBMC samples collected from the infected macaque and …

Identification And Characterization Of A New Kaposi’S Sarcoma-Associated Herpesvirus Replication And Transcription Activator (Rta)- Responsive Element Involved In Rta-Mediated Transactivation, Hui-Ju Wen, Veenu Minhas, Charles Wood

Nebraska Center for Virology: Faculty Publications

Kaposi’s sarcoma-associated herpesvirus (KSHV) replication and transcription activator (RTA) is well established as a key transcriptional activator that regulates the KSHV life cycle from latency to lytic replication. It is expressed immediately after infection and activates a number of viral genes leading to virus replication. The RTA-responsive element (RRE) in the RTA target gene promoters is critical for RTA to mediate this transactivation. A number of non-conserved RREs have been identified in various RTA-responsive promoters, and AT-rich sequences have been proposed to serve as RTA targets, but no consensus RRE sequence has been identified so far. Two nonconserved RREs (RRE1 …