Medicine and Health Sciences Commons^™

Advancing The Future Of Nursing: A Report By The Building Academic Geriatric Nursing, Jennifer L. Bellot, Dana Carthron, Melissa O'Connor, Karen Rose, Casey Shillam, Janet Van Cleave, Amy Vogelsmeier

College of Nursing Faculty Papers & Presentations

In the United States, the number of older adults will double during the next 25 years (United States Census Bureau, 2008). This dramatic demographic shift is changing the landscape of health care practice as more people live longer with multiple chronic conditions. To better prepare nurses to care for this future population, the John A. Hartford Foundation partnered with the American Academy of Nursing in 2000 to launch the Building Academic Geriatric Nursing Capacity (BAGNC) program. Since that time, 251 scholarships and fellowships have been awarded to nurses to advance geriatric nursing education, research, and practice. In 2009, …

Key Neurological And Neurochemical Features In A Model Of Repetitive Concussions: Implications For Post-Concussion Headache, C. Macolino, B. Daiutolo, A. Tyburski, Melanie B. Elliott

Department of Neurosurgery Faculty Papers

Introduction

Incidence rates for concussion will continue to grow along with the increasing awareness and improvements in diagnosis. Headache is a hallmark feature of post-concussion syndrome. Post-concussion headache (PCH) is highly prevalent in the military with as high as 97.8% reporting having headaches¹. occurring in up to 85% of athletes following ^2-4. In the Military and sports, return to duty or play guidelines state that a soldier/player should be asymptomatic before returning to physical activity. However, headache following concussion is commonly dismissed. PCH can be a new headache resulting from head trauma or worsening of pre-existing headache …

Cerebral Blood Flow Dynamics And Head-Of-Bed Changes In The Setting Of Subarachnoid Hemorrhage., David K Kung, Nohra El-Chalouhi, Md, Pascal Jabbour, Md, Robert M Starke, Aaron Dumont, Md, H Richard Winn, Matthew A Howard, David M Hasan

Department of Neurosurgery Faculty Papers

Head-of-bed (HOB) elevation is usually restricted in patients with aneurysmal subarachnoid hemorrhage (SAH). The goal of this study is to correlate HOB changes (0° and 90°) with cerebral blood flow using transcranial Doppler (TCD) and thermal diffusion probe in SAH patients. Thirteen patients with SAH were prospectively enrolled in the study. Eight patients underwent placement of a thermal diffusion probe for regional CBF measurement. CBF values were measured with the patients in flat (0°) and upright sitting positions (90°) at days 3, 7, and 10. The average increase in blood flow velocity when changing HOB from 0° to 90° was …

Gender Differences In Attitudes Impeding Colorectal Cancer Screening., Paul Ritvo, Ronald E. Myers, Lawrence Paszat, Mardie Serenity, Daniel F Perez, Linda Rabeneck

Department of Medical Oncology Faculty Papers

BACKGROUND: Colorectal cancer screening (CRCS) is the only type of cancer screening where both genders reduce risks by similar proportions with identical procedures. It is an important context for examining gender differences in disease-prevention, as CRCS significantly reduces mortality via early detection and prevention. In efforts to increase screening adherence, there is increasing acknowledgment that obstructive attitudes prevent CRCS uptake. Precise identification of the gender differences in obstructive attitudes is necessary to improve uptake promotion. This study randomly sampled unscreened, screening - eligible individuals in Ontario, employing semi-structured interviews to elicit key differences in attitudinal obstructions towards colorectal cancer screening …

Presence Of Anaplastic Lymphoma Kinase In Inflammatory Breast Cancer., Fredika M Robertson, Emanuel F Petricoin Iii, Steven J Van Laere, Francois Bertucci, Khoi Chu, Sandra V Fernandez, Zhaomei Mu, Katherine Alpaugh, Jianming Pei, Rita Circo, Julia Wulfkuhle, Zaiming Ye, Kimberly M Boley, Hui Liu, Ricardo Moraes, Xuejun Zhang, Ruggero Demaria, Sanford H Barsky, Guoxian Sun, Massimo Cristofanilli

Department of Medical Oncology Faculty Papers

Although Inflammatory Breast Cancer (IBC) is recognized as the most metastatic variant of locally advanced breast cancer, the molecular basis for the distinct clinical presentation and accelerated program of metastasis of IBC is unknown. Reverse phase protein arrays revealed activation of the receptor tyrosine kinase, anaplastic lymphoma kinase (ALK) and biochemically-linked downstream signaling molecules including JAK1/STAT3, AKT, mTor, PDK1, and AMPKβ in pre-clinical models of IBC. To evaluate the clinical relevance of ALK in IBC, analysis of 25 IBC patient tumors using the FDA approved diagnostic test for ALK genetic abnormalities was performed. These studies revealed that 20/25 (80%) had …

Dysregulated Methylation At Imprinted Genes In Prostate Tumor Tissue Detected By Methylation Microarray., Daniel I Jacobs, Yingying Mao, Alan Fu, William Kevin Kelly, Yong Zhu

Department of Medical Oncology Faculty Papers

BACKGROUND: Imprinting is an important epigenetic regulator of gene expression that is often disrupted in cancer. While loss of imprinting (LOI) has been reported for two genes in prostate cancer (IGF2 and TFPI2), disease-related changes in methylation across all imprinted gene regions has not been investigated.

METHODS: Using an Illumina Infinium Methylation Assay, we analyzed methylation of 396 CpG sites in the promoter regions of 56 genes in a pooled sample of 12 pairs of prostate tumor and adjacent normal tissue. Selected LOI identified from the array was validated using the Sequenom EpiTYPER assay for individual samples and further confirmed …

Ezh2 Knockdown Suppresses The Growth And Invasion Of Human Inflammatory Breast Cancer Cells., Zhaomei Mu, Hua Li, Sandra V Fernandez, Katherine R Alpaugh, Rugang Zhang, Massimo Cristofanilli

Department of Medical Oncology Faculty Papers

INTRODUCTION: Inflammatory breast cancer (IBC) is the most metastatic variant of breast cancer with the poorest survival in all types of breast cancer patients and presently therapeutic targets for IBC are very limited. Enhancer of zeste homolog 2 (EZH2) is frequently expressed in human IBC and its expression positively correlates with worse clinical outcome. However, the molecular basis for EZH2 promoting IBC has not been explored. Here, we investigated the functional role of EZH2 in IBC cells by examining the effects of its knockdown on the formation of tumor spheroids and invasion of these cells in vitro and in vivo …

The Complex Transcriptional Landscape Of The Anucleate Human Platelet., Paul F. Bray, Steven E. Mckenzie, Leonard Edelstein, Srikanth Nagalla, Kathleen Delgrosso, Adam Ertel, Joan Kupper, Yi Jing, Eric R. Londin, Phillipe Loher, Huang-Wen Chen, Paolo Fortina, Isidore Rigoutsos

Cardeza Foundation for Hematologic Research

BACKGROUND: Human blood platelets are essential to maintaining normal hemostasis, and platelet dysfunction often causes bleeding or thrombosis. Estimates of genome-wide platelet RNA expression using microarrays have provided insights to the platelet transcriptome but were limited by the number of known transcripts. The goal of this effort was to deep-sequence RNA from leukocyte-depleted platelets to capture the complex profile of all expressed transcripts.

RESULTS: From each of four healthy individuals we generated long RNA (≥40 nucleotides) profiles from total and ribosomal-RNA depleted RNA preparations, as well as short RNA (<40 >nucleotides) profiles. Analysis of ~1 billion reads revealed that coding …

Perioperative Management Of Interscalene Block In Patients With Lung Disease., Eric S. Schwenk, Kishor Gandhi, Eugene R. Viscusi

Department of Anesthesiology Faculty Papers

Interscalene nerve block impairs ipsilateral lung function and is relatively contraindicated for patients with lung impairment. We present a case of an 89-year-old female smoker with prior left lung lower lobectomy and mild to moderate lung disease who presented for right shoulder arthroplasty and insisted on regional anesthesia. The patient received a multimodal perioperative regimen that consisted of a continuous interscalene block, acetaminophen, ketorolac, and opioids. Surgery proceeded uneventfully and postoperative analgesia was excellent. Pulmonary physiology and management of these patients will be discussed. A risk/benefit discussion should occur with patients having impaired lung function before performance of interscalene blocks. …

Rhob Controls Coordination Of Adult Angiogenesis And Lymphangiogenesis Following Injury By Regulating Vezf1-Mediated Transcription., Damien Gerald, Irit Adini, Sharon Shechter, Carole Perruzzi, Joseph Varnau, Benjamin Hopkins, Shiva Kazerounian, Peter Kurschat, Stephanie Blachon, Santosh Khedkar, Mandrita Bagchi, David Sherris, George C Prendergast, Michael Klagsbrun, Heidi Stuhlmann, Alan C Rigby, Janice A Nagy, Laura E Benjamin

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Mechanisms governing the distinct temporal dynamics that characterize post-natal angiogenesis and lymphangiogenesis elicited by cutaneous wounds and inflammation remain unclear. RhoB, a stress-induced small GTPase, modulates cellular responses to growth factors, genotoxic stress and neoplastic transformation. Here we show, using RhoB null mice, that loss of RhoB decreases pathological angiogenesis in the ischaemic retina and reduces angiogenesis in response to cutaneous wounding, but enhances lymphangiogenesis following both dermal wounding and inflammatory challenge. We link these unique and opposing roles of RhoB in blood versus lymphatic vasculatures to the RhoB-mediated differential regulation of sprouting and proliferation in primary human blood versus …

Ash2 Acts As An Ecdysone Receptor Coactivator By Stabilizing The Histone Methyltransferase Trr., Albert Carbonell, Alexander Mazo, Florenci Serras, Montserrat Corominas

Department of Biochemistry and Molecular Biology Faculty Papers

The molting hormone ecdysone triggers chromatin changes via histone modifications that are important for gene regulation. On hormone activation, the ecdysone receptor (EcR) binds to the SET domain-containing histone H3 methyltransferase trithorax-related protein (Trr). Methylation of histone H3 at lysine 4 (H3K4me), which is associated with transcriptional activation, requires several cofactors, including Ash2. We find that ash2 mutants have severe defects in pupariation and metamorphosis due to a lack of activation of ecdysone-responsive genes. This transcriptional defect is caused by the absence of the H3K4me3 marks set by Trr in these genes. We present evidence that Ash2 interacts with Trr …

Molecular Determinants Of Epidermal Growth Factor Binding: A Molecular Dynamics Study., Jeffrey M Sanders, Matthew E Wampole, Mathew L. Thakur, Eric Wickstrom

Department of Biochemistry and Molecular Biology Faculty Papers

The epidermal growth factor receptor (EGFR) is a member of the receptor tyrosine kinase family that plays a role in multiple cellular processes. Activation of EGFR requires binding of a ligand on the extracellular domain to promote conformational changes leading to dimerization and transphosphorylation of intracellular kinase domains. Seven ligands are known to bind EGFR with affinities ranging from sub-nanomolar to near micromolar dissociation constants. In the case of EGFR, distinct conformational states assumed upon binding a ligand is thought to be a determining factor in activation of a downstream signaling network. Previous biochemical studies suggest the existence of both …

The Tip Of The Tail Needle Affects The Rate Of Dna Delivery By Bacteriophage P22., Justin C Leavitt, Lasha Gogokhia, Eddie B Gilcrease, Anshul Bhardwaj, Gino Cingolani, Sherwood R Casjens

Department of Biochemistry and Molecular Biology Faculty Papers

The P22-like bacteriophages have short tails. Their virions bind to their polysaccharide receptors through six trimeric tailspike proteins that surround the tail tip. These short tails also have a trimeric needle protein that extends beyond the tailspikes from the center of the tail tip, in a position that suggests that it should make first contact with the host's outer membrane during the infection process. The base of the needle serves as a plug that keeps the DNA in the virion, but role of the needle during adsorption and DNA injection is not well understood. Among the P22-like phages are needle …

Structural Implications For Selective Targeting Of Parps., Jamin D Steffen, Md, Jonathan Brody, Md, Roger S Armen, Md, John M Pascal, Md

Department of Biochemistry and Molecular Biology Faculty Papers

Poly(ADP-ribose) polymerases (PARPs) are a family of enzymes that use NAD(+) as a substrate to synthesize polymers of ADP-ribose (PAR) as post-translational modifications of proteins. PARPs have important cellular roles that include preserving genomic integrity, telomere maintenance, transcriptional regulation, and cell fate determination. The diverse biological roles of PARPs have made them attractive therapeutic targets, which have fueled the pursuit of small molecule PARP inhibitors. The design of PARP inhibitors has matured over the past several years resulting in several lead candidates in clinical trials. PARP inhibitors are mainly used in clinical trials to treat cancer, particularly as sensitizing agents …

Identification Of Phosphorylation Sites In The Cooh-Terminal Tail Of The Μ-Opioid Receptor., Ying-Ju Chen, Sue Oldfield, Adrian J. Butcher, Andrew B. Tobin, Kunal Saxena, Vsevolod V. Gurevich, Jeffrey L. Benovic, Graeme Henderson, Eamonn Kelly

Department of Biochemistry and Molecular Biology Faculty Papers

Phosphorylation is considered a key event in the signalling and regulation of the μ opioid receptor (MOPr). Here, we used mass spectroscopy to determine the phosphorylation status of the C-terminal tail of the rat MOPr expressed in human embryonic kidney 293 (HEK-293) cells. Under basal conditions, MOPr is phosphorylated on Ser(363) and Thr(370), while in the presence of morphine or [D-Ala2, NMe-Phe4, Gly-ol5]-enkephalin (DAMGO), the COOH terminus is phosphorylated at three additional residues, Ser(356) , Thr(357) and Ser(375). Using N-terminal glutathione S transferase (GST) fusion proteins of the cytoplasmic, C-terminal tail of MOPr and point mutations of the same, we …

Infective Endocarditis Epidemiology Over Five Decades: A Systematic Review., Leandro Slipczuk, J Nicolas Codolosa, Carlos D Davila, Abel Romero-Corral, Jeong Yun, Gregg S. Pressman, Vincent M. Figueredo

Division of Cardiology Faculty Papers

AIMS: To Assess changes in infective endocarditis (IE) epidemiology over the last 5 decades.

METHODS AND RESULTS: We searched the published literature using PubMed, MEDLINE, and EMBASE from inception until December 2011.

DATA FROM: Einstein Medical Center, Philadelphia, PA were also included. Criteria for inclusion in this systematic review included studies with reported IE microbiology, IE definition, description of population studied, and time frame. Two authors independently extracted data and assessed manuscript quality. One hundred sixty studies (27,083 patients) met inclusion criteria. Among hospital-based studies (n=142; 23,606 patients) staphylococcal IE percentage increased over time, with coagulase-negative staphylococcus (CNS) increasing over …

Targeted Therapies In The Treatment Of Advanced Hepatocellular Carcinoma., Zhengyu Wei, Cataldo Doria, Yuan Liu

Department of Surgery Faculty Papers

Hepatocellular carcinoma (HCC) is the most common liver cancer and the third leading cause of cancer death. It has been a major worldwide health problem with more new cases being diagnosed each year. The current available therapies for patients with advanced HCC are extremely limited. Therefore, it is of great clinical interests to develop more effective therapies for systemic treatment of advanced HCC. Several promising target-based drugs have been tested in a number of clinical trials. One breakthrough of these efforts is the approved clinical use of sorafenib in patients with advanced HCC. Targeted therapies are becoming an attractive option …

Purpose And Criteria For Blood Smear Scan, Blood Smear Examination, And Blood Smear Review., Gene Gulati, Jinming Song, Alina Dulau Florea, Jerald Gong

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

A microscopic examination of an appropriately prepared and well-stained blood smear by a knowledgeable laboratory professional is necessary and clinically useful in a number of circumstances and for a variety of reasons. In this article, an attempt is made to delineate the purpose and criteria for blood smear examination in a variety of circumstances that are encountered in everyday laboratory hematology practice. A blood smear scan serves to at least (a) verify the flagged automated hematology results and (b) determine if a manual differential leukocyte count needs to be performed. Blood smear examination/manual differential leukocyte count with complete blood count …

Ethanol Diverts Early Neuronal Differentiation Trajectory Of Embryonic Stem Cells By Disrupting The Balance Of Lineage Specifiers., Rosa Sánchez-Alvarez, Saurabh Gayen, Rajanikanth Vadigepalli, Helen Anni

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Ethanol is a toxin responsible for the neurodevelopmental deficits of Fetal Alcohol Spectrum Disorders (FASD). Recent evidence suggests that ethanol modulates the protein expression of lineage specifier transcription factors Oct4 (Pou5f1) and Sox2 in early stages of mouse embryonic stem (ES) cell differentiation. We hypothesized that ethanol induced an imbalance in the expression of Oct4 and Sox2 in early differentiation, that dysregulated the expression of associated and target genes and signaling molecules and diverted cells from neuroectodermal (NE) formation.

METHODOLOGY/PRINCIPAL FINDINGS: We showed modulation by ethanol of 33 genes during ES cell differentiation, using high throughput microfluidic dynamic array …

Cis And Trans Regulatory Mechanisms Control Ap2-Mediated B Cell Receptor Endocytosis Via Select Tyrosine-Based Motifs., Kathleen Busman-Sahay, Lisa Drake, Anand Sitaram, Michael Marks, James R Drake

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Following antigen recognition, B cell receptor (BCR)-mediated endocytosis is the first step of antigen processing and presentation to CD4+ T cells, a crucial component of the initiation and control of the humoral immune response. Despite this, the molecular mechanism of BCR internalization is poorly understood. Recently, studies of activated B cell-like diffuse large B cell lymphoma (ABC DLBCL) have shown that mutations within the BCR subunit CD79b leads to increased BCR surface expression, suggesting that CD79b may control BCR internalization. Adaptor protein 2 (AP2) is the major mediator of receptor endocytosis via clathrin-coated pits. The BCR contains five putative AP2-binding …

The Contributions Of Hif-Target Genes To Tumor Growth In Rcc., Ting Zhang, Xiaohua Niu, Lili Liao, Eun-Ah Cho, Haifeng Yang

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Somatic mutations or loss of expression of tumor suppressor VHL happen in the vast majority of clear cell Renal Cell Carcinoma, and it's causal for kidney cancer development. Without VHL, constitutively active transcription factor HIF is strongly oncogenic and is essential for tumor growth. However, the contribution of individual HIF-responsive genes to tumor growth is not well understood. In this study we examined the contribution of important HIF-responsive genes such as VEGF, CCND1, ANGPTL4, EGLN3, ENO2, GLUT1 and IGFBP3 to tumor growth in a xenograft model using immune-compromised nude mice. We found that the suppression of VEGF or CCND1 impaired …

Chronic Ethanol Feeding Alters Mirna Expression Dynamics During Liver Regeneration., Rachael P Dippold, Rajanikanth Vadigepalli, Gregory E. Gonye, Biswanath Patra, Jan B. Hoek

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Adaptation to chronic ethanol (EtOH) treatment of rats results in a changed functional state of the liver and greatly inhibits its regenerative ability, which may contribute to the progression of alcoholic liver disease.

METHODS: In this study, we investigated the effect of chronic EtOH intake on hepatic microRNA (miRNA) expression in male Sprague-Dawley rats during the initial 24 hours of liver regeneration following 70% partial hepatectomy (PHx) using miRNA microarrays. miRNA expression during adaptation to EtOH was investigated using RT-qPCR. Nuclear factor kappa B (NFκB) binding at target miRNA promoters was investigated with chromatin immunoprecipitation.

RESULTS: Unsupervised clustering of …

Is The Reporting Timeliness Gap For Avian Flu And H1n1 Outbreaks In Global Health Surveillance Systems Associated With Country Transparency?, Feng-Jen Tsai, Eva Tseng, Chang-Chuan Chan, Hiko Tamashiro, Sandrine Motamed, André C Rougemont

Division of Internal Medicine Faculty Papers & Presentations

BACKGROUND: This study aims to evaluate the length of time elapsed between reports of the same incidents related to avian flu and H1N1 outbreaks published by the WHO and ProMED-mail, the two major global health surveillance systems, before and after the amendment of the International Health Regulations in 2005 (IHR 2005) and to explore the association between country transparency and this timeliness gap.

METHODS: We recorded the initial release dates of each report related to avian flu or H1N1 listed on the WHO Disease Outbreak News site and the matching outbreak report from ProMED-mail, a non-governmental program for monitoring emerging …

Cervical Assessment By Ultrasound For Preventing Preterm Delivery., Vincenzo Berghella, Jason K. Baxter Md, Mscp, Nancy W Hendrix

Department of Obstetrics and Gynecology Faculty Papers

BACKGROUND: Measurement of cervical length (CL) by transvaginal ultrasound (TVU) is predictive of preterm birth (PTB). It is unclear if this screening test is effective for prevention of PTB.

OBJECTIVES: To assess the effectiveness of antenatal management based on transvaginal ultrasound of cervical length (TVU CL) screening for preventing PTB.

SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 August 2012), reviewed the reference lists of all articles and contacted experts in the field for additional and ongoing trials.

SELECTION CRITERIA: Published and unpublished randomized controlled trials including pregnant women between the gestational ages of 14 …

Warning Signal: Unaware Of An In Absentia Conviction, South African Cancer Specialist Jailed On Return To The United Arab Emirates., Philip R Cohen, Razelle Kurzrock, Lawrence Parish

Department of Dermatology and Cutaneous Biology Faculty Papers

In 2002, Dr. Cyril Karabus, a specialist in pediatric cancers and retired head of the Oncology and Hematology Unit of Red Cross Children's Hospital in Capetown, South Africa, spent a brief locum at Sheikh Khalifa Medical City, a hospital in Abu Dhabi in the United Arab Emirates (UAE). He was there for only 5 weeks, during which time he treated a young girl who died of acute myeloblastic leukemia. After Karabus returned home, the girl's father complained to police about his daughter's death, and Karabus was convicted of murder in absentia. Karabus knew nothing of the charges or of the …

Genodermatoses: Differential Diagnosis Of Cutaneous Elastin Disorders: Cutis Laxa Vs. Pseudoxanthoma Elasticum, Jouni Uitto

Department of Dermatology and Cutaneous Biology Faculty Papers

No abstract provided.

Genodermatoses, Jouni Uitto

Department of Dermatology and Cutaneous Biology Faculty Papers

No abstract provided.

A Genome-Wide Methylation Study On Essential Hypertension In Young African American Males., Xiaoling Wang, Bonita Falkner, Haidong Zhu, Huidong Shi, Shaoyong Su, Xiaojing Xu, Ashok Kumar Sharma, Yanbin Dong, Frank Treiber, Bernard Gutin, Gregory Harshfield, Harold Snieder

Department of Medicine Faculty Papers

OBJECTIVE: There is emerging evidence from animal studies suggesting a key role for methylation in the pathogenesis of essential hypertension. However, to date, very few studies have investigated the role of methylation in the development of human hypertension, and none has taken a genome-wide approach. Based on the recent studies that highlight the involvement of inflammation in the development of hypertension, we hypothesize that changes in DNA methylation of leukocytes are involved in the pathogenesis of hypertension.

METHOD & RESULTS: We conducted a genome-wide methylation analysis on 8 hypertensive cases and 8 normotensive age-matched controls aged 14-23 years and performed …

De Novo Fibrillary Glomerulonephritis (Fgn) In A Renal Transplant With Chronic Hepatitis C., E J Filippone, Christine Chmielewski, Rakesh Gulati, Eric Newman, John Farber

Department of Medicine Faculty Papers

Chronic hepatitis C viremia (HepC) has been associated with numerous renal manifestations both in native kidneys and in the setting of renal transplantation. Glomerulonephritis (GN) of the renal allograft in the setting of HepC most commonly manifests as type 1 membranoproliferative GN (MPGN), either representing recurrence of the original disease or arising de novo. Other GNs were reported after transplantation in the patient with HepC including membranous nephropathy and thrombotic microangiopathy, as well as an enhanced susceptibility to transplant glomerulopathy. We describe the first case of de novo fibrillary GN in a renal transplant patient with HepC where the primary …

Ddx5 Facilitates Hiv-1 Replication As A Cellular Co-Factor Of Rev., Xiuxia Zhou, Juan Luo, Lisa Mills, Shuangxin Wu, Ting Pan, Guannan Geng, Jim Zhang, Haihua Luo, Chao Liu, Hui Zhang

Department of Medicine Faculty Papers

HIV-1 Rev plays an important role in the late phase of HIV-1 replication, which facilitates export of unspliced viral mRNAs from the nucleus to cytoplasm in infected cells. Recent studies have shown that DDX1 and DDX3 are co-factors of Rev for the export of HIV-1 transcripts. In this report, we have demonstrated that DDX5 (p68), which is a multifunctional DEAD-box RNA helicase, functions as a new cellular co-factor of HIV-1 Rev. We found that DDX5 affects Rev function through the Rev-RRE axis and subsequently enhances HIV-1 replication. Confocal microscopy and co-immunoprecipitation analysis indicated that DDX5 binds to Rev and this …