Microbiology Commons^™

Fluoroquinolone And Macrolide Co-Resistance In Clinical Isolates Of Campylobacter Species: A 15-Year Study In Karachi, Pakistan, Seema Irfan, A Ahmad, D Guhar, E Khan, Fasial Malik, Syed Mahmood, Afia Zafar

Department of Pathology and Laboratory Medicine

Fluoroquinolone and macrolide antibiotics are generally considered as first-line drugs for the treatment of severe campylobacteriosis. This study was conducted to analyse the trend of erythromycin and ofloxacin resistance among Campylobacter spp. isolated from stool specimens over a period of 15 years (1992-2007) at The Aga Khan University clinical laboratory in Karachi, Pakistan. A total of 83 396 stool specimens were processed, with a 14% isolation rate for enteric pathogens. The isolation rate of Campylobacter spp. was low during 1992-93 (6%-13%), peaked in 1996 (46%), then ranged from 20% to 40%. We report a rising trend in ofloxacin resistance, re-emergence …

Histologic Findings In Biopsies/Resection Specimens From The Small Intestine With Special Emphasis On Celiac Disease: Experience From A Developing Country In South Asia, Huma Arshad, Zubair Ahmad

Department of Pathology and Laboratory Medicine

Biopsies from the small intestine especially the duodenum are now being performed much more frequently than in the past. The most frequent reason for performing duodenal biopsies is to evaluate for malabsorption. In the last few years, increased awareness has resulted in more biopsies sent for evaluation of malabsorption, especially celiac disease (CD). In the duodenum, features of malabsorption (increased intraepithelial lymphocytes, villous shortening, and atrophy) were the most common histologic finding seen in 63.4% of cases. Serum tTG levels were available for correlation in 52.8% of cases. In patients with confirmed CD, 53.4% were MARSH IIIb, and 29.5% were …

Allogeneic Stem Cell Transplantation In Acute Myeloid Leukemia, Natasha Bahadur Ali, Salman Adil, Mohammad Usman Shaikh, Nehal Masood

Department of Pathology and Laboratory Medicine

We report a case series of 12 patients with acute myeloid leukemia who underwent allogeneic stem cell transplant with a matched related donor. Male to female ratio was 1:1. The main complication post-transplant was graft-versus-host disease (n=7 patients). Transplant-related mortality involved one patient; cause of death was multi-organ failure. After a median follow up of 36.0±11.3 months, overall survival was 16%.

Multifocal Venous Thrombosis In Behcet’S Disease, Lena Jafri, Nosheen Nasir, Aysha Almas

Department of Pathology and Laboratory Medicine

Behcet's disease is a multisystem inflammatory vascular disorder with a chronic course characterized by recurrent oral and genital ulcers, eye lesion, arthritis and skin lesions. It has a typically waxing and waning course. The cause and pathogenesis of the disease are unclear and specific treatment is not available. A 39 years old man presented with rash, ocular manifestation and left leg swelling. He was found to have deep venous thrombosis of left leg along with recurrent cerebral venous thrombosis. He was a known case of Behcet's disease since 3 years and had been on anticoagulants since then.

Macrolide And Fluoroquinolone Resistance In Helicobacter Pylori Isolates: An Experience At A Tertiary Care Centre In Pakistan, Sana Rajper, Erum Khan, Zubair Ahmad, Syed Muhammad Zaheer Alam, Adil Akbar, Rumina Hasan

Department of Pathology and Laboratory Medicine

Objective:
To assess fluoroquinolone and clarithromycin susceptibility pattern along with the types of genomic mutations involved in the resistance of Helicobacter pylori isolates.
Methods:
The cross-sectional study was conducted at the Department of Pathology and Microbiology, Aga Khan University Hospital, Karachi, from June 2009 to July 2010, and comprised 162 gastric biopsy samples which were tested with GenoTypeHelicoDR (Hain Lifescience GmbH, Germany), a reverse hybridisation multiplex polymerase chain reaction (PCR) line probe assay (LiPA). Also, 23S rRNA (ribosomal ribonucleic acid) gene was analysed with three-point mutations at A2146G, A2146C and A2147G for clarithromycin, and gyrA gene was analyzed at two …

Diagnostic Utility Of Anti-Citrullinated Protein Antibody And Its Comparison With Rheumatoid Factor In Rheumatoid Arthritis, Aysha Habib, Lena Jafri, M. Ahraz Hussain, Saliha Ishaq

Department of Pathology and Laboratory Medicine

Objective: To assess the diagnostic utility of anti-citrullinated protein antibody (anti-CCP) in rheumatoid arthritis (RA) and compare it with rheumatoid factor (RF). Study Design: Analytical study. Place and Duration of Study: Section of Chemical Pathology, Department of Pathology and Microbiology and Medicine, the Aga Khan University, Karachi, from January to May 2010. Methodology: A review of medical records of patients presenting to the clinics with complaints of muscular or joint pains and who were tested for their serum anti-CCP was done. Inclusion criteria were presence of clinical synovitis in at least one joint and an absence of alternative diagnosis. Patients …

Consumption Of High Ω-3 Fatty Acid Diet Suppressed Prostate Tumorigenesis In C3(1) Tag Mice, Juliana Akinsete, Gabriela Ion, Theodore Witte, W. Hardman

Gabriela Ion

Prostate cancer incidence and mortality are high in the Western world and high ω-6/ω-3 PUFA in the Western diet may be a contributing factor. We investigated whether changing from a diet that approximates ω-6 fat content of the Western diet to a high ω-3 fat diet at adulthood might reduce prostate cancer risk. Female SV 129 mice that had consumed a high ω-6 diet containing corn oil for 2 weeks were bred with homozygous C3(1)Tag transgenic male mice. All male offspring were weaned to the corn oil diet (CO) until postpuberty when half of the male offspring were transferred to …

Neurosteroid-Mediated Regulation Of Brain Innate Immunity In Hiv/Aids: Dhea-S Suppresses Neurovirulence, Amber Paul, Ferdinand G. Maingat, Maria J. Polyak, Pornpun Vivithanaporn, Farshid Noorbakhsh, Samir Ahboucha, Glen B. Baker, Keir Pearson, Christopher Power

Publications

Neurosteroids are cholesterol-derived molecules synthesized within the brain, which exert trophic and protective actions. Infection by human and feline immunodeficiency viruses (HIV and FIV, respectively) causes neuroinflammation and neurodegeneration, leading to neurological deficits. Secretion of neuroinflammatory host and viral factors by glia and infiltrating leukocytes mediates the principal neuropathogenic mechanisms during, although the effect of neurosteroids on these processes is unknown. We investigated the interactions between neurosteroid mediated effects and lentivirus infection outcomes. Analyses of HIV-infected uninfected human brains disclosed a reduction in neurosteroid synthesis enzyme expression. Human neurons exposed to supernatants from HIV macrophages exhibited suppressed enzyme expression without …

Global Analysis Of Gene Expression Changes During Retinoic Acid-Induced Growth Arrest And Differentiation Of Melanoma: Comparison To Differentially Expressed Genes In Melanocytes Vs Melanoma, Mary Estler, Goran Boskovic, James Denvir, Sarah Miles, Donald Primerano, Richard Niles

James Denvir

BACKGROUND: The incidence of malignant melanoma has significantly increased over the last decade. Some of these malignancies are susceptible to the growth inhibitory and pro-differentiating effects of all-trans-retinoic acid (RA). The molecular changes responsible for the biological activity of RA in melanoma are not well understood. RESULTS: In an analysis of sequential global gene expression changes during a 4-48 h RA treatment of B16 mouse melanoma cells, we found that RA increased the expression of 757 genes and decreased the expression of 737 genes. We also compared the gene expression profile (no RA treatment) between non-malignant melan-a mouse melanocytes and …

Consumption Of High Ω-3 Fatty Acid Diet Suppressed Prostate Tumorigenesis In C3(1) Tag Mice, Juliana A. Akinsete, Gabriela Ion, Theodore R. Witte, W. Elaine Hardman

Elaine Hardman Ph.D.

Prostate cancer incidence and mortality are high in the Western world and high ω-6/ω-3 PUFA in the Western diet may be a contributing factor. We investigated whether changing from a diet that approximates ω-6 fat content of the Western diet to a high ω-3 fat diet at adulthood might reduce prostate cancer risk. Female SV 129 mice that had consumed a high ω-6 diet containing corn oil for 2 weeks were bred with homozygous C3(1)Tag transgenic male mice. All male offspring were weaned to the corn oil diet (CO) until postpuberty when half of the male offspring were transferred to …

Global Analysis Of Gene Expression Changes During Retinoic Acid-Induced Growth Arrest And Differentiation Of Melanoma: Comparison To Differentially Expressed Genes In Melanocytes Vs Melanoma, Mary H. Estler, Goran Boskovic, James Denvir, Sarah Miles, Donald A. Primerano, Richard M. Niles

Donald A. Primerano

BACKGROUND: The incidence of malignant melanoma has significantly increased over the last decade. Some of these malignancies are susceptible to the growth inhibitory and pro-differentiating effects of all-trans-retinoic acid (RA). The molecular changes responsible for the biological activity of RA in melanoma are not well understood. RESULTS: In an analysis of sequential global gene expression changes during a 4-48 h RA treatment of B16 mouse melanoma cells, we found that RA increased the expression of 757 genes and decreased the expression of 737 genes. We also compared the gene expression profile (no RA treatment) between non-malignant melan-a mouse melanocytes and …

Global Analysis Of Gene Expression Changes During Retinoic Acid-Induced Growth Arrest And Differentiation Of Melanoma: Comparison To Differentially Expressed Genes In Melanocytes Vs Melanoma, Mary H. Estler, Goran Boskovic, James Denvir, Sarah Miles, Donald A. Primerano, Richard M. Niles

Richard M. Niles

BACKGROUND: The incidence of malignant melanoma has significantly increased over the last decade. Some of these malignancies are susceptible to the growth inhibitory and pro-differentiating effects of all-trans-retinoic acid (RA). The molecular changes responsible for the biological activity of RA in melanoma are not well understood. RESULTS: In an analysis of sequential global gene expression changes during a 4-48 h RA treatment of B16 mouse melanoma cells, we found that RA increased the expression of 757 genes and decreased the expression of 737 genes. We also compared the gene expression profile (no RA treatment) between non-malignant melan-a mouse melanocytes and …

Role Of Interleukin-17 In The Adaptive Immune Response In Lyme Arthritis, Emily Siebers

Theses and Dissertations

Lyme arthritis is a devastating symptom of Lyme borreliosis that causes severe inflammation of the synovial joints. Interleukin-17 (IL-17) plays a role in the pathogenesis of various arthritides, including, possibly, Lyme arthritis, by causing the expression of genes involved in the production of inflammatory cytokines by synoviocytes. However, the cellular sources of IL-17 in the context of Borrelia burgdorferi infection are unknown, as are the effects of these cells on the development of arthritis and stimulation of humoral immunity through the production of borreliacidal antibodies. Using multiple models of Lyme arthritis, the hypothesis that IL-17 produced by CD4+ cells contributes …

Line Probe Assay For Detection Of Rifampicin And Isoniazid Resistant Tuberculosis In Pakistan, Joveria Qais Farooqi, Erum Khan, Syed Muhammed Zaheer Alam, Asho Ali, Zahra Hasan, Rumina Hasan

Department of Pathology and Laboratory Medicine

Objective:
To assess the efficacy of a line-probe assay delta (LiPA) as rapid diagnostic test for early detection of drug-resistant tuberculosis compared to conventional susceptibility methods in Pakistan.
Methods:
Resistance to rifampicin (RIF) and isoniazid (INH) in 108 smear-positive pulmonary tuberculosis samples was detected using a line-probe assay [GenoType MTBDRplus (Hain Lifescience, GmbH, Nehren, Germany)] at the clinical microbiology laboratory of Aga Khan University Hospital in May, 2009. Results were compared with susceptibilities performed while using agar proportion.
Results:
In comparison to the agar proportion method, the detection rate and specificity of resistance using MTBDR plus was 92.5% and 98.2% …

Epoxide-Mediated Cifr Repression Of Cif Gene Expression Utilizes Two Binding Sites In Pseudomonas Aeruginosa, Alicia E. Ballok, Christopher D. Bahl, Emily L. Dolben, Allia K. Lindsay, Jessica D. St. Laurent, Deborah Hogan, Dean Madden, George A. O'Toole

Dartmouth Scholarship

Pseudomonas aeruginosa secretes an epoxide hydrolase virulence factor that reduces the apical membrane expression of ABC transporters such as the cystic fibrosis transmembrane conductance regulator (CFTR). This virulence factor, named CFTR inhibitory factor (Cif), is regulated by a TetR-family, epoxide-responsive repressor known as CifR via direct binding and repression. We identified two sites of CifR binding in the intergenic space between cifR and morB, the first gene in the operon containing the cif gene. We have mapped these binding sites and found they are 27 bp in length, and they overlap the -10 and +1 sites of both the cifR …

Two Boundaries Separate Borrelia Burgdorferi Populations In North America, Gabriele Margos, Jean I. Tsao, Santiago Castillo-Ramirez, Yvette A. Girard, Anne G. Hoen

Dartmouth Scholarship

Understanding the spread of infectious diseases is crucial for implementing effective control measures. For this, it is important to obtain information on the contemporary population structure of a disease agent and to infer the evolutionary processes that may have shaped it. Here, we investigate on a continental scale the population structure of Borrelia burgdorferi, the causative agent of Lyme borreliosis (LB), a tick-borne disease, in North America. We test the hypothesis that the observed d population structure is congruent with recent population expansions and that these were preceded by bottlenecks mostly likely caused by the near extirpation in the 1900s …

Corneal Replication Is An Interferon Response-Independent Bottleneck For Virulence Of Herpes Simplex Virus 1 In The Absence Of Virion Host Shutoff, Tracy J. Pasieka, Vineet D. Menachery, Pamela C. Rosato, David A. Leib

Dartmouth Scholarship

Herpes simplex viruses lacking the virion host shutoff function (Δvhs) are avirulent and hypersensitive to type I and type II interferon (IFN). In this study, we demonstrate that even in the absence of IFN responses in AG129 (IFN-αβγR^−/−) mice, Δvhs remains highly attenuated via corneal infection but is fully virulent via intracranial infection. The data demonstrate that the interferon-independent inherent replication defect of Δvhs has a significant impact upon peripheral replication and neuroinvasion.

The Prevalence And Identity Of Chlamydia-Specific Ige In Children With Asthma And Other Chronic Respiratory Symptoms, Katir K. Patel, Erica A. Anderson, Paul S. Salva, Wilmore C. Webley

Wilmore C Webley

Background Recent studies have confirmed the presence of viable Chlamydia in the bronchoalveolar lavage (BAL) fluid of pediatric patients with airway hyperresponsiveness. While specific IgG and IgM responses to C. pneumoniae are well described, the response and potential contribution of Ag-specific IgE are not known. The current study sought to determine if infection with Chlamydia triggers the production of pathogen-specific IgE in children with chronic respiratory diseases which might contribute to inflammation and pathology.

Methods We obtained BAL fluid and serum from pediatric respiratory disease patients who were generally unresponsive to corticosteroid treatment as well as sera from age-matched control …

Response Of A Single 'Mega Intramuscular Dose' Of Vitamin D On Serum 25ohd And Parathyroid Hormone Levels, Aysha Habib, Dileep K Rohra, Shakil A Saghir, Shamsa K Udani, Richard Wood, Abdul Jabbar

Department of Pathology and Laboratory Medicine

Objective: To determine the changes produced in serum 25OHD and iPTH levels after 600,000 IU of injection cholecalciferol in volunteers. Study Design: Interventional study. Place and Duration of Study: Section of Chemical Pathology, Department of Pathology and Microbiology, the Aga Khan University Hospital, Karachi, from June 2009 - June 2010. Methodology: Volunteers of either gender aged 18-40 years with known 25OHD, calcium (Ca), creatinine (Cr) and phosphorous (P) levels were included in the study. Subjects on therapy like vitamin D and calcium supplements, corticosteroids or anti-epileptic medicines, primary hyperparathyroidism and hypercalcaemia, with co-morbidity like renal failure, liver disease and history …

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 …

Hemoglobin E Syndromes In Pakistani Population., Bushra Moiz, Amna Nasir, Anila Rashid, Tariq Moatter, Mashhooda Rasool Hashmi

Department of Pathology and Laboratory Medicine

Background:Hemoglobin E is an important hemoglobin variant with a worldwide distribution. A number of hemoglobinopathies have been reported from Pakistan. However a comprehensive description of hemoglobin E syndromes for the country was never made. This study aimed to describe various hemoglobin E disorders based on hematological parameters and chromatography. The sub-aim was to characterize hemoglobin E at molecular level.

Methods:

This was a hospital based study conducted prospectively for a period of one year extending from January 1 to December 31, 2008. EDTA blood samples were analyzed for completed blood counts and hemoglobin variants through automated hematology analyzer and …

Early Events In Herpes Simplex Virus Lifecycle With Implications For An Infection Of Lifetime, Sarah Salameh '12, Urmi Sheth '12, Deepak Shukla

Student Publications & Research

Affecting a large percentage of human population herpes simplex virus (HSV) types -1 and -2 mainly cause oral, ocular, and genital diseases. Infection begins with viral entry into a host cell, which may be preceded by viral “surfing” along filopodia. Viral glycoproteins then bind to one or more of several cell surface receptors, such as herpesvirus entry mediator (HVEM), nectin-1, 3-O sulfated heparan sulfate (3-OS HS), paired immunoglobulin-like receptor, and non-muscle myosin-IIA. At least five viral envelope glycoproteins participate in entry and these include gB, gC, gD and gH-gL. Post-entry, these glycoproteins may also facilitate cell-to-cell spread of the virus, …

Consumption Of High Ω-3 Fatty Acid Diet Suppressed Prostate Tumorigenesis In C3(1) Tag Mice, Juliana A. Akinsete, Gabriela Ion, Theodore R. Witte, W. Elaine Hardman

Biochemistry and Microbiology

Prostate cancer incidence and mortality are high in the Western world and high ω-6/ω-3 PUFA in the Western diet may be a contributing factor. We investigated whether changing from a diet that approximates ω-6 fat content of the Western diet to a high ω-3 fat diet at adulthood might reduce prostate cancer risk. Female SV 129 mice that had consumed a high ω-6 diet containing corn oil for 2 weeks were bred with homozygous C3(1)Tag transgenic male mice. All male offspring were weaned to the corn oil diet (CO) until postpuberty when half of the male offspring were transferred to …

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 …

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 …