Hepatitis C and COVID-19 Global Concerns: Sustained Financing and Expanded Access to Testing and Pangenotypic Treatments Needed to Recover the Path to Elimination

Total Page:16

File Type:pdf, Size:1020Kb

Hepatitis C and COVID-19 Global Concerns: Sustained Financing and Expanded Access to Testing and Pangenotypic Treatments Needed to Recover the Path to Elimination TREATMENT ACTION GROUP POLICY BRIEF 2021 www.treatmentactiongroup.org Hepatitis C and COVID-19 Global Concerns: Sustained Financing and Expanded Access to Testing and Pangenotypic Treatments Needed to Recover the Path to Elimination By Bryn Gay, Suraj Madoori, Annette Gaudino, and Elizabeth Lovinger Edited by Candida Hadley INTRODUCTION Enormous amounts of public funding and health be leveraged to inform COVID-19 R&D, clinical resources have been reallocated from address- trials, and equitable and affordable access strat- ing the blood-borne hepatitis C virus (HCV) egies. Investments in COVID-19 can also aid with to respond to the novel SARS-CoV-2 virus/ rolling out the HCV response and strengthening COVID-19 pandemic. This has complicated the the capacity and infrastructure needed for both delivery of essential services and made scale-up epidemics. of HCV testing and treatment even less likely. As governments and donors send emergency COVID-19 relief aid to countries and jurisdictions, COVID-19 IS THREATENING THE sustained financing and expanded access to pre- vention, testing, and pangenotypic treatments INCREMENTAL HEPATITIS C PROGRESS for HCV (that treat all genetic variations of the NEARLY EVERYWHERE virus) need to be included to recover the path to Global HCV Diagnosis and Treatment Gaps elimination. We can expect COVID-19 to worsen HCV1 and Investments in research and development of overdose-related2 death tolls because people HCV treatments, diagnostic tools, and lab in- who are disproportionately affected by HCV, frastructure have directly led to the creation of particularly people who use drugs, are more goods that are being put to use for COVID-19. likely to be isolated, miss medical appointments, and lack access to essential support systems. As governments and donors send The pandemic has also interrupted outreach and emergency COVID-19 relief aid to prevention programs, including harm reduction countries and jurisdictions, sustained services, screening campaigns, and routine health visits that confirm HCV diagnoses and identify financing and expanded access to new cases. Interruptions to essential health pro- prevention, testing, and pangenotypic grams are part of efforts to reduce people’s risk treatments for HCV (that treat all of exposure to the SARS-CoV-2 virus. genetic variations of the virus) need Before COVID-19, global treatment uptake to be included to recover the path to among the general population was already elimination. dismal, with a few exceptions, namely Australia, France, Georgia, and Italy (see Figure 1). Since Lessons from HCV on how to address a largely the groundbreaking, highly effective direct-act- undiagnosed and untreated infection that in- ing antiviral (DAA) sofosbuvir (Sovaldi) for HCV cludes numerous barriers between patients and became available in 2013, more than 90%3 (or effective cures can inform policies on accessing 67 million people) of the world’s estimated 71 COVID-19 technologies, such as vaccines. Com- million people living with chronic HCV remain munity engagement and advocacy networks can untreated. 2 TREATMENT ACTION GROUP POLICY BRIEF In the U.S., an estimated 63% of Americans re- generic competition has reduced prices to less main untreated,4 in large part due to high pre- than US$100 per treatment course, with costs scription drug prices, prior authorization require- significantly lower in Egypt, India, and Pakistan. ments by payors, and restrictions against treating High drug prices should no longer be a barrier to individuals who are actively using drugs or alco- treatment; diversifying generic competition and hol or experiencing early stage liver disease. Ge- lifting treatment restrictions in all countries will neric HCV treatments are not as widely available help more people start treatment earlier. Further- and accessible in high-income settings, including more, the lack of international donor funding and in the U.S., due to patent monopolies. Outside national scale-up remain major challenges. high-income countries, within seven years, global Figure 1. Treatment Uptake in 20 Select Countries in 20185,6 Indonesia 0.15% Burundi 0.37% Malaysia 0.68% Russian Federation 0.73% Argentina 0.95% Thailand 1.69% Chile 1.78% Bulgaria 3.37% Tunisia 4.04% Romania 4.20% Lebanon 7.50% Iran, Islamic Rep. 8.58% Rwanda 11.42% Brazil 11.67% Poland 13.17% Pakistan 14.43% United Kingdom 14.55% Italy 19.76% Georgia 25.73% Australia 32.17% France 33.14% 0 5 10 15 20 25 30 35 Interim progress reports by the Coalition for Few or virtually no people who inject Global Hepatitis Elimination focus on the 20 drugs have been treated in the countries with the highest HCV burdens. That majority of countries. According to is, if these 20 countries meet the WHO targets by 2030, HCV could effectively be eliminated. the mapCrowd database, less than However, other than Europe, most regions did 2% of people who inject drugs have not see a major decline in HCV-related mortal- been treated even in countries where ity in the years 2015–2019.7 The progress reports elimination plans have been launched. highlight the expansion of generic treatment access, mostly in low- and middle-income coun- The availability of the cure in countries has little tries. However, other than in Europe, the majority impact if harm reduction coverage is lacking and of countries do not have more than one needle the people who are most in need and dispropor- and syringe program (NSP).8 tionately affected by hepatitis C do not access 3 TREATMENT ACTION GROUP POLICY BRIEF treatment and care.9 Few or virtually no people We need to treat 5 million people every who inject drugs have been treated in the ma- year worldwide to achieve hepatitis C jority of countries. According to the mapCrowd database, less than 2% of people who inject drugs elimination by 2030 have been treated,10 even in countries where and sobriety—in more than half of U.S. states,13,14 elimination plans have been launched. the U.S. is failing in its HCV response and will We need to treat 5 million people every year miss the 2030 WHO global targets (see Figure 15 worldwide to achieve hepatitis C elimination by 2). Recent modeling shows only three states (6%; Connecticut, South Carolina, and Wash- 2030.11 ington) are on track to reduce new HCV cases In the U.S., we need to treat an estimated by 80%, and only 16 states (31%) are on track 16 173,514 people each year to reach the 2030 to treat 80% of patients with HCV by 2030. treatment target.12 Some progress has been made, however, with 45 states (87%) expected to diagnose 90% of their Despite lifting insurance barriers and treatment HCV infections and 46 states (88%) on track to restrictions—including levels of liver scarring reduce HCV-related mortality by 65% by 2030. Figure 2. Year of Elimination17 WA ME MT ND VT OR MN NH ID WI NY MA SD RI WY MI CT IA PA NE NV OH NJ IL IN DE UT MD CA CO WV VA DC KS MO KY YEAR: NC < 2030 AZ OK TN 2031-2035 NM AR SC 2036-2040 AL MS GA 2041-2049 > 2050 TX LA AK FL HI PR *The estimation may be less accurate owing to the small number of patients with HCV in the area. Increasing treatment initiation requires increasing HEALTH NEEDS FOR PEOPLE WITH the number of people who are tested and diag- HCV IN THE COVID-19 ERA nosed with HCV. An estimated 80% of people living with HCV remain undiagnosed worldwide People who recover from COVID-19 have been and, of those, more than 95% live in low- and mid- shown to have elevated liver enzymes;20 people liv- dle-income countries.18 COVID-19 has derailed ef- ing with viral hepatitis, liver scarring, liver disease, forts to screen, newly diagnose, and start people or other hepatic conditions will need to monitor on treatment. Modeling estimates19 of the global their liver function following their recovery from impact of COVID-19 predict that a one-year gap coronavirus. It is unclear if people with viral hepa- and delay in HCV services will result in 44,800 titis have worse health outcomes from COVID-19, additional cases of liver cancer and 72,300 addi- however, preliminary studies21 show that COVID-19 tional liver-related deaths, mostly in high-income has higher mortality rates for people with chronic countries, between 2020 and 2030. liver disease and cirrhosis: 63.2% of people with 4 TREATMENT ACTION GROUP POLICY BRIEF new decompensated liver disease died from CO- HCV PROGRAMMATIC IMPACTS VID-19 compared to 26.2% who did not have new OF COVID-19 decompensated liver disease. The pandemic has paused global hepatitis C test- Protecting lung health, in addition to liver health, ing and treatment and disrupted healthcare and is important for people living with HCV, particu- harm reduction services, including needle and sy- larly people who formerly or currently vape or ringe programs (NSP) and provision of opioid sub- smoke tobacco or cannabis or inject or use other stitution therapy (OST). The results of a 32-country substances. Taking opioids slows breathing, de- survey25 conducted by the World Hepatitis Alliance creases oxygen in the blood, and can decrease between March 30 and May 4, 2020 further dem- lung capacity. Methamphetamine use can tighten onstrate the severe impacts on global hepatitis blood vessels and contributes to pulmonary dam- programs: 94% (121 of 132 total respondents; 50% age and hypertension.22 Financing and sustaining from the U.S.) responded that their viral hepatitis peer-driven harm reduction and counseling ser- services were affected by COVID-19. Lack of test- vices can assist with strategies to better protect ing was reported by 66 (or 65%) of 101 respon- dents; this was attributed to avoiding healthcare lung and liver health.
Recommended publications
  • Viral Hepatitis Testing Effective Date: January 1, 2012
    Viral Hepatitis Testing Effective Date: January 1, 2012 Scope This guideline provides guidance for the use of laboratory tests to diagnose acute and chronic viral hepatitis in adults (> 19 years) in the primary care setting. General Considerations for Ordering Laboratory Tests Prior to ordering tests for hepatitis, consider the patient’s history, age, risk factors (see below), hepatitis vaccination status, and any available previous hepatitis test results. Risk Factors for Viral Hepatitis include: • Substance use (includes sharing drug snorting, smoking or injection equipment) • High-risk sexual activity or sexual partner with viral hepatitis • Travel to or from high-risk hepatitis endemic areas or exposure during a local outbreak • Immigration from hepatitis B and/or C endemic countries • Household contact with an infected person especially if personal items (e.g., razors, toothbrushes, nail clippers) are shared • Recipient of unscreened blood products* • Needle-stick injury or other occupational exposure (e.g., healthcare workers) • Children born to mothers with chronic hepatitis B or C infection • Attendance at daycare • Contaminated food or water (hepatitis A only) • Tattoos and body piercing • History of incarceration • HIV or other sexually transmitted infection • Hemodialysis *screening of donated blood products for hepatitis C (anti-HCV) began in 1990 in Canada.1 Types of Viral Hepatitis Hepatitis A: causes acute but not chronic hepatitis Hepatitis B: causes acute and chronic hepatitis Hepatitis C: causes chronic hepatitis but rarely manifests as acute hepatitis Hepatitis D: rare and only occurs in patients infected with hepatitis B Hepatitis E: clinically similar to hepatitis A, mostly restricted to endemic areas and occasionally causes chronic infection in immunosuppressed people Others: e.g.
    [Show full text]
  • Prevention & Control of Viral Hepatitis Infection
    Prevention & Control of Viral Hepatitis Infection: A Strategy for Global Action © World Health Organization 2011. All rights reserved. The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. The mention of specific companies or of certain manufacturers’ products does not imply that they are endorsed or recommended by the World Health Organization in preference to others of a similar nature that are not mentioned. Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters. All reasonable precautions have been taken by WHO to verify the information contained in this publication. However, the published material is being distributed without warranty of any kind, either express or implied. The responsibility for the interpretation and use of the material lies with the reader. In no event shall the World Health Organization be liable for damages arising from its use. Table of contents Disease burden 02 What is viral hepatitis? 05 Prevention & control: a tailored approach 06 Global Achievements 08 Remaining challenges 10 World Health Assembly: a mandate for comprehensive prevention & control 13 WHO goals and strategy
    [Show full text]
  • 2016 Research in Action Awards
    TREATMENT ACTION GROUP The Board of Trustees 2016 RESEARCH IN ACTION AWARDS and staff of amfAR, The Foundation Treatment Action Group’s (TAG’s) annual Research in Action Awards honor activists, scientists, philanthropists and creative artists who have made for AIDS Research extraordinary contributions in the fight against AIDS. Tonight’s awards ceremony is a fundraiser to support TAG’s programs and provides a forum for honoring heroes of the epidemic. salute the recipients of the HONOREES LEVI STRAUSS & CO. for advancing human rights and the fight 2016 TAG Research in Action Awards against HIV/AIDS ROSIE PEREZ actor/activist MARGARET RUSSELL award-winning design journalist/editor, Levi Strauss & Co. cultural leader and accomplished advocate for HIV prevention and care BARBARA HUGHES longtime AIDS activist and dedicated Rosie Perez President of TAG’s Board since 1996 HOSTS Margaret Russell JENNA WOLFE lifestyle and fitness expert BRUCE VILANCH comedy writer, songwriter, actor and Emmy ® Barbara Hughes Award winner THURSDAY, NOVEMBER 17, 2016 6PM Cocktails and Hors d’Oeuvres 7PM Awards Presentation SLATE www.amfar.org 54 West 21st Street New York City TAG ad 102716.indd 1 10/27/16 3:17 PM TAG 2016 LIMITED ART EDITION RIAA 2016 CO-CHAIRS SCOTT CAMPBELL Executive Director, Elton John AIDS Foundation DICK DADEY Executive Director, Citizens Union JOY TOMCHIN Founder of Public Square Films, Executive Producer of How to Survive a Plague and the upcoming documentary Sylvia and Marsha RIAA 2016 HONORARY CHAIRS 2014 RIAA honoree ALAN CUMMING and GRANT SHAFFER 2009 RIAA honoree DAVID HYDE PIERCE and BRIAN HARGROVE ROSALIND FOX SOLOMON Animal Landscape, 1979 Archival pigment print | 15 1/2 x 15 1/2 inches | 8-ply mat + granite welded metal frame + uv plexi 23 1/2 x 23 inches | Edition of 15 + 3 AP's | ©Rosalind Fox Solomon, www.rosalindsolomon.com RIAA 2016 COMMITTEE Courtesy of Bruce Silverstein Gallery Joy Episalla, Chair for Projects Plus, Inc.
    [Show full text]
  • The Role of Hepatitis C Virus in Hepatocellular Carcinoma U
    Viruses in cancer cell plasticity: the role of hepatitis C virus in hepatocellular carcinoma U. Hibner, D. Gregoire To cite this version: U. Hibner, D. Gregoire. Viruses in cancer cell plasticity: the role of hepatitis C virus in hepato- cellular carcinoma. Contemporary Oncology, Termedia Publishing House, 2015, 19 (1A), pp.A62–7. 10.5114/wo.2014.47132. hal-02187396 HAL Id: hal-02187396 https://hal.archives-ouvertes.fr/hal-02187396 Submitted on 2 Jun 2021 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Distributed under a Creative Commons Attribution - NonCommercial - ShareAlike| 4.0 International License Review Viruses are considered as causative agents of a significant proportion of human cancers. While the very Viruses in cancer cell plasticity: stringent criteria used for their clas- sification probably lead to an under- estimation, only six human viruses the role of hepatitis C virus are currently classified as oncogenic. In this review we give a brief histor- in hepatocellular carcinoma ical account of the discovery of on- cogenic viruses and then analyse the mechanisms underlying the infectious causes of cancer. We discuss viral strategies that evolved to ensure vi- Urszula Hibner1,2,3, Damien Grégoire1,2,3 rus propagation and spread can alter cellular homeostasis in a way that increases the probability of oncogen- 1Institut de Génétique Moléculaire de Montpellier, CNRS, UMR 5535, Montpellier, France ic transformation and acquisition of 2Université Montpellier 2, Montpellier, France stem cell phenotype.
    [Show full text]
  • The Use of Non-Human Primates in Research in Primates Non-Human of Use The
    The use of non-human primates in research The use of non-human primates in research A working group report chaired by Sir David Weatherall FRS FMedSci Report sponsored by: Academy of Medical Sciences Medical Research Council The Royal Society Wellcome Trust 10 Carlton House Terrace 20 Park Crescent 6-9 Carlton House Terrace 215 Euston Road London, SW1Y 5AH London, W1B 1AL London, SW1Y 5AG London, NW1 2BE December 2006 December Tel: +44(0)20 7969 5288 Tel: +44(0)20 7636 5422 Tel: +44(0)20 7451 2590 Tel: +44(0)20 7611 8888 Fax: +44(0)20 7969 5298 Fax: +44(0)20 7436 6179 Fax: +44(0)20 7451 2692 Fax: +44(0)20 7611 8545 Email: E-mail: E-mail: E-mail: [email protected] [email protected] [email protected] [email protected] Web: www.acmedsci.ac.uk Web: www.mrc.ac.uk Web: www.royalsoc.ac.uk Web: www.wellcome.ac.uk December 2006 The use of non-human primates in research A working group report chaired by Sir David Weatheall FRS FMedSci December 2006 Sponsors’ statement The use of non-human primates continues to be one the most contentious areas of biological and medical research. The publication of this independent report into the scientific basis for the past, current and future role of non-human primates in research is both a necessary and timely contribution to the debate. We emphasise that members of the working group have worked independently of the four sponsoring organisations. Our organisations did not provide input into the report’s content, conclusions or recommendations.
    [Show full text]
  • Rational Engineering of HCV Vaccines for Humoral Immunity
    viruses Review To Include or Occlude: Rational Engineering of HCV Vaccines for Humoral Immunity Felicia Schlotthauer 1,2,†, Joey McGregor 1,2,† and Heidi E Drummer 1,2,3,* 1 Viral Entry and Vaccines Group, Burnet Institute, Melbourne, VIC 3004, Australia; [email protected] (F.S.); [email protected] (J.M.) 2 Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC 3000, Australia 3 Department of Microbiology, Monash University, Clayton, VIC 3800, Australia * Correspondence: [email protected]; Tel.: +61-392-822-179 † These authors contributed equally to this work. Abstract: Direct-acting antiviral agents have proven highly effective at treating existing hepatitis C infections but despite their availability most countries will not reach the World Health Organization targets for elimination of HCV by 2030. A prophylactic vaccine remains a high priority. Whilst early vaccines focused largely on generating T cell immunity, attention is now aimed at vaccines that gen- erate humoral immunity, either alone or in combination with T cell-based vaccines. High-resolution structures of hepatitis C viral glycoproteins and their interaction with monoclonal antibodies isolated from both cleared and chronically infected people, together with advances in vaccine technologies, provide new avenues for vaccine development. Keywords: glycoprotein E2; vaccine development; humoral immunity Citation: Schlotthauer, F.; McGregor, J.; Drummer, H.E To Include or 1. Introduction Occlude: Rational Engineering of HCV Vaccines for Humoral Immunity. The development of direct-acting antiviral agents (DAA) with their ability to cure Viruses 2021, 13, 805. https:// infection in >95% of those treated was heralded as the key to eliminating hepatitis C globally.
    [Show full text]
  • Research Directions After the First Hepatitis C Vaccine Efficacy Trial
    viruses Review Where to Next? Research Directions after the First Hepatitis C Vaccine Efficacy Trial Christopher C. Phelps 1 , Christopher M. Walker 1,2 and Jonathan R. Honegger 1,2,*,† 1 Center for Vaccines and Immunity, Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, OH 43205, USA; [email protected] (C.C.P.); [email protected] (C.M.W.) 2 Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH 43210, USA * Correspondence: [email protected] † Current address: Abigail Wexner Research Institute at Nationwide Children’s Hospital, 700 Children’s Drive, WA4020, Columbus, OH 43205, USA. Abstract: Thirty years after its discovery, the hepatitis C virus (HCV) remains a leading cause of liver disease worldwide. Given that many countries continue to experience high rates of transmission despite the availability of potent antiviral therapies, an effective vaccine is seen as critical for the elimination of HCV. The recent failure of the first vaccine efficacy trial for the prevention of chronic HCV confirmed suspicions that this virus will be a challenging vaccine target. Here, we examine the published data from this first efficacy trial along with the earlier clinical and pre-clinical studies of the vaccine candidate and then discuss three key research directions expected to be important in ongoing and future HCV vaccine development. These include the following: 1. design of novel immunogens that generate immune responses to genetically diverse HCV genotypes and subtypes, 2. strategies to elicit broadly neutralizing antibodies against envelope glycoproteins in addition to cytotoxic and helper T cell responses, and 3.
    [Show full text]
  • All Qatar Residents to Get Covid Vaccine Free
    INDEX QATAR 2-6,12 COMMENT 10 BUSINESS | Page 1 QATAR | Page 12 ARAB WORLD 7 BUSINESS 1-12 Qatar private INTERNATIONAL 7-9,11 SPORTS 1-8 Last Covid-19 sector bounces DOW JONES QE NYMEX patient back on lift ing discharged 28,148.64 9,956.66 39.36 of Covid-19 +465.83 +3.15 +2.31 from Lebsear +1.68% +0.03% +6.23% curbs: QFC Latest Figures Field Hospital published in QATAR since 1978 TUESDAY Vol. XXXXI No. 11693 October 6, 2020 Safar 19, 1442 AH GULF TIMES www. gulf-times.com 2 Riyals PM offers condolences to Amir of Kuwait HE the Prime Minister and Minister of Interior Sheikh Khalid bin Khalifa bin Abdulaziz al-Thani yesterday off ered condolences to the Amir of Kuwait, Sheikh Nawaf al-Ahmad al-Jaber al-Sabah, on the death of Sheikh Sabah al-Ahmad al-Jaber al-Sabah, praying to Allah to have mercy on the soul of the deceased and to rest it in peace in Paradise. The prime minister also off ered condolences to members of the ruling family and ranking off icials. Ministers and members of the off icial delegation accompanying the prime minister also off ered their condolences. Two held for violating PM meets Afghan president home quarantine rules Competent authorities arrested yesterday two people who violated All Qatar residents to the requirements of the home quarantine, which they committed to following, in accordance with the procedures of the health authorities in the country. The get Covid vaccine free two persons being referred to prosecution are: Albert Mondano Oshavillo and Nasser Ghaidan By Ayman Adly is not yet clear whether the upcoming Mohamed al-Hatheeth al-Qahtani.
    [Show full text]
  • Hepatitis A, B, and C: Learn the Differences
    Hepatitis A, B, and C: Learn the Differences Hepatitis A Hepatitis B Hepatitis C caused by the hepatitis A virus (HAV) caused by the hepatitis B virus (HBV) caused by the hepatitis C virus (HCV) HAV is found in the feces (poop) of people with hepa- HBV is found in blood and certain body fluids. The virus is spread HCV is found in blood and certain body fluids. The titis A and is usually spread by close personal contact when blood or body fluid from an infected person enters the body virus is spread when blood or body fluid from an HCV- (including sex or living in the same household). It of a person who is not immune. HBV is spread through having infected person enters another person’s body. HCV can also be spread by eating food or drinking water unprotected sex with an infected person, sharing needles or is spread through sharing needles or “works” when contaminated with HAV. “works” when shooting drugs, exposure to needlesticks or sharps shooting drugs, through exposure to needlesticks on the job, or from an infected mother to her baby during birth. or sharps on the job, or sometimes from an infected How is it spread? Exposure to infected blood in ANY situation can be a risk for mother to her baby during birth. It is possible to trans- transmission. mit HCV during sex, but it is not common. • People who wish to be protected from HAV infection • All infants, children, and teens ages 0 through 18 years There is no vaccine to prevent HCV.
    [Show full text]
  • Understanding Human Astrovirus from Pathogenesis to Treatment
    University of Tennessee Health Science Center UTHSC Digital Commons Theses and Dissertations (ETD) College of Graduate Health Sciences 6-2020 Understanding Human Astrovirus from Pathogenesis to Treatment Virginia Hargest University of Tennessee Health Science Center Follow this and additional works at: https://dc.uthsc.edu/dissertations Part of the Diseases Commons, Medical Sciences Commons, and the Viruses Commons Recommended Citation Hargest, Virginia (0000-0003-3883-1232), "Understanding Human Astrovirus from Pathogenesis to Treatment" (2020). Theses and Dissertations (ETD). Paper 523. http://dx.doi.org/10.21007/ etd.cghs.2020.0507. This Dissertation is brought to you for free and open access by the College of Graduate Health Sciences at UTHSC Digital Commons. It has been accepted for inclusion in Theses and Dissertations (ETD) by an authorized administrator of UTHSC Digital Commons. For more information, please contact [email protected]. Understanding Human Astrovirus from Pathogenesis to Treatment Abstract While human astroviruses (HAstV) were discovered nearly 45 years ago, these small positive-sense RNA viruses remain critically understudied. These studies provide fundamental new research on astrovirus pathogenesis and disruption of the gut epithelium by induction of epithelial-mesenchymal transition (EMT) following astrovirus infection. Here we characterize HAstV-induced EMT as an upregulation of SNAI1 and VIM with a down regulation of CDH1 and OCLN, loss of cell-cell junctions most notably at 18 hours post-infection (hpi), and loss of cellular polarity by 24 hpi. While active transforming growth factor- (TGF-) increases during HAstV infection, inhibition of TGF- signaling does not hinder EMT induction. However, HAstV-induced EMT does require active viral replication.
    [Show full text]
  • 1 Title: Interim Report of a Phase 2 Randomized Trial of a Plant
    medRxiv preprint doi: https://doi.org/10.1101/2021.05.14.21257248; this version posted May 17, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. 1 Title: Interim Report of a Phase 2 Randomized Trial of a Plant-Produced Virus-Like Particle 2 Vaccine for Covid-19 in Healthy Adults Aged 18-64 and Older Adults Aged 65 and Older 3 Authors: Philipe Gobeil1, Stéphane Pillet1, Annie Séguin1, Iohann Boulay1, Asif Mahmood1, 4 Donald C Vinh 2, Nathalie Charland1, Philippe Boutet3, François Roman3, Robbert Van Der 5 Most4, Maria de los Angeles Ceregido Perez3, Brian J Ward1,2†, Nathalie Landry1† 6 Affiliations: 1 Medicago Inc., 1020 route de l’Église office 600, Québec, QC, Canada, G1V 7 3V9; 2 Research Institute of the McGill University Health Centre, 1001 Decarie St, Montreal, 8 QC H4A 3J1; 3 GlaxoSmithKline Biologicals SA (Vaccines), Avenue Fleming 20, 1300 Wavre, 9 Belgium; 4 GlaxoSmithKline Biologicals SA (Vaccines), rue de l’Institut 89, 1330 Rixensart, 10 Belgium; † These individuals are equally credited as senior authors. 11 * Corresponding author: Nathalie Landry, 1020 Route de l’Église, Bureau 600, Québec, Qc, 12 Canada, G1V 3V9; Tel. 418 658 9393; Fax. 418 658 6699; [email protected] 13 Abstract 14 The rapid spread of SARS-CoV-2 globally continues to impact humanity on a global scale with 15 rising morbidity and mortality. Despite the development of multiple effective vaccines, new 16 vaccines continue to be required to supply ongoing demand.
    [Show full text]
  • Host Cell Functions in Vesicular Stomatitis Virus Replication Phat X
    University of Nebraska - Lincoln DigitalCommons@University of Nebraska - Lincoln Papers in Veterinary and Biomedical Science Veterinary and Biomedical Sciences, Department of 2016 Host Cell Functions In Vesicular Stomatitis Virus Replication Phat X. Dinh University of Nebraska - Lincoln Anshuman Das University of Nebraska-Lincoln Asit K. Pattnaik University of Nebraska - Lincoln, [email protected] Follow this and additional works at: https://digitalcommons.unl.edu/vetscipapers Part of the Biochemistry, Biophysics, and Structural Biology Commons, Cell and Developmental Biology Commons, Immunology and Infectious Disease Commons, Medical Sciences Commons, Veterinary Microbiology and Immunobiology Commons, and the Veterinary Pathology and Pathobiology Commons Dinh, Phat X.; Das, Anshuman; and Pattnaik, Asit K., "Host Cell Functions In Vesicular Stomatitis Virus Replication" (2016). Papers in Veterinary and Biomedical Science. 237. https://digitalcommons.unl.edu/vetscipapers/237 This Article is brought to you for free and open access by the Veterinary and Biomedical Sciences, Department of at DigitalCommons@University of Nebraska - Lincoln. It has been accepted for inclusion in Papers in Veterinary and Biomedical Science by an authorized administrator of DigitalCommons@University of Nebraska - Lincoln. Published in Biology and Pathogenesis of Rhabdo and Filoviruses Copyright © 2016 World Scientific Publishing Co Pte Ltd digitalcommons.unl.edu HOST CELL FUNCTIONS IN VESICULAR STOMATITIS VIRUS REPLICATION Phat X. Dinh, Anshuman Das, and Asit K. Pattnaik School of Veterinary Medicine and Biomedical Sciences and the Nebraska Center for Virology, University of Nebraska-Lincoln, 109 Morrison Life Science Research Center, 4240 Fair Street, Lincoln, * Nebraska 68583, USA E-mail: [email protected] Summary Vesicular stomatitis virus (VSV), the prototypic rhabdovirus, has been used as an excellent paradigm for understanding the mechanisms of virus replication, pathogenesis, host response to virus infection and also for myriads of studies on cellular and molecular biology.
    [Show full text]