Arboviruses_2023 (1).pptx

INTRODUCTION TO ARBOVIRUSES : FLAVIVIRIDAE AND BUNYAVIRIDAE Michael E. Woods, Ph.D. October 30, 2023 LEARNING OBJECTIVES By the end of this session you should be able to:  Classify the Flaviviridae and Bunyaviridae based on structure and replication, geographic origin and epidemiology, host rese...

INTRODUCTION TO ARBOVIRUSES : FLAVIVIRIDAE AND BUNYAVIRIDAE Michael E. Woods, Ph.D. October 30, 2023 LEARNING OBJECTIVES By the end of this session you should be able to:  Classify the Flaviviridae and Bunyaviridae based on structure and replication, geographic origin and epidemiology, host reservoir type, and primary vector(s) of transmission  Name 2-3 virulence factors and discuss the potential role of each in arbovirus virulence  Explain the mechanism of antibody-mediated enhancement in the pathogenesis of dengue hemorrhagic fever/shock syndrome  Describe the general clinical syndromes and morphology of lesions associated with arbovirus fevers  Compare and contrast the techniques used to diagnose arbovirus infections  Discuss the types of treatment and prevention for arbovirus infections including the mechanism of action or protection Required readings Recommended readings  Murray, Rosenthal and Pfaller,  Posted in LEO Medical Microbiology, 9th Edition, pp. Chapter 52 ARBOVIRUSES ARE A DIVERSE GROUP OF ARTHROPODBORNE VIRUSES (NOT A FORMAL PHYLOGENETIC CLASSIFICATION) Arboviruses Single-stranded positive-sense RNA Family: Togaviridae Genus: alphavirus Family: Flaviviridae Genus: flavivirus Single-stranded negative sense RNA Family: Bunyaviridae Genus: orthobunyavirus nairovirus phlebovirus tospovirus Family: Rhabdoviridae Genus: vesiculovirus Family: Orthomyxoviridae Genus: thogotovirus Double-stranded RNA Family: Reoviridae Genus: orbivirus coltivirus Virus Family Genus Distribution Host Vector CFR Dengue virus Tropics worldwide Humans Aedes mosquito Yellow Fever virus Sub-Saharan Africa, Central and South America Primates Aedes and Haemagogus mosquito Zika disease virus Central and South America, Caribbean, South Pacific, Africa, India, Southeast Asia Humans Aedes aegypti and Aedes albopictus <1% West Nile disease virus Africa, Europe, Middle East, North America and West Asia Birds Culex spp. of mosquitoes <1% Omsk hemorrhagic fever virus Western Siberia (Russia) Muskrats and voles Dermacentor and Ixodes ticks 0.5%–3% Kyasanur Forest Disease virus Karnataka State, India Hemaphysalis spinigera tick Hemaphysalis spinigera tick 2%–10% Flaviviridae Flavivirus 1%–5% 15%–30% Alkhurma disease virus Saudi Arabia, Egypt ? Ornithidoros savignyi and Hyalomma dromedary ticks Chikungunya virus Americas, Africa, Asia, Europe and the Indian and Pacific Oceans Humans Aedes mosquito <1% North and South America, Caribbean Birds Aedes, Culiseta mosquitoes 30% Eastern Europe, Central Asia, Middle East, Sub-Saharan Africa, Indian subcontinent Hyalomma tick Hyalomma tick 30%–60% Phlebovirus Africa, Middle East Mosquitoes Mosquitoes Hantavirus* East Asia (China, Russia and Korea) Striped field mouse (Apodemus agrarius) Striped field mouse (Apodemus agrarius) Togaviridae Alphavirus Eastern Equine Encephalitis virus Crimean-Congo hemorrhagic fever virus Rift Valley fever virus Hantaan virus* (and others) Nairovirus Bunyavirida e ? 1% 5%–15% FLAVIVIRUS GENOMIC AND STRUCTURAL ORGANIZATION  Positive-sense RNA genome with a 5’ RNA cap (i.e., mRNA)  Entire genome is translated as a single polyprotein  Polyprotein is cleaved by host and viral proteases Structural proteins • C (capsid) • prM (membrane precursor) • E (envelope) Non-structural proteins • NS1 – viral replication • NS2 – polyprotein processing • NS3 – viral replication and polyprotein processing • NS4 – viral replication • NS5 – RNA capping and RNA-dependent RNA polymerase http://viralzone.expasy.org/all_by_species/24.html FLAVIVIRUSES REPLICATE IN ASSOCIATION WITH THE ER; MATURE THROUGH THE GOLGI S. Mukhopadhyay, R.J. Kuhn and M.G. Rossman, “A structural perspective of the flavivirus life cycle,” Nature Reviews Microbiology, January 2005, Vol. 3, Muller and Young, “The flavivirus NS1 protein: Molecular and structural biology, immunology, role in pathogenesis and application as a diagnostic biomarker,” Antiviral Research, May 2013, Vol. 98, No. 2, DENGUE VIRUS IS THE MOST COMMON MOSQUITO-BORNE VIRUS IN THE WORLD  Estimated 390 million infections per year, of which 96 million manifest clinically  500,000 progress to DHF  25,000 deaths  Four closely-related but distinct serotypes exist (DEN-1, -2, -3 and 4)  Infection with one serotype confers lifelong immunity against that serotype  Cross-immunity is only partial and temporary  Co-circulation of multiple dengue serotypes is increasing, which may contribute to a rise in the occurrence of severe dengue DENGUE VIRUS PRIMARILY CIRCULATES IN A CYCLE BETWEEN MAN AND MOSQUITO Predicted distribution of Aedes aegypti Barrett, A.D.T., Medical Microbiology, 51, 520-536 Copyright © 2012 © 2012 Elsevier Ltd. All rights reserved, except Chapter 21 © Crown Copyright 2012/DSTL Kraemer et al., “The global distribution of the arbovirus vectors Aedes aegypti and Ae. Albopictus,” eLIFE, 2015, Vol. 4, e08347 DENGUE VIRUS INFECTION CAUSES DENGUE FEVER; MAY PROGRESS TO DENGUE HEMORRHAGIC FEVER (DHF) OR DENGUE SHOCK SYNDROME (DSS) 20% untreated CFR Dengue and Dengue Hemorrhagic Fever Ooi, Eng Eong, Tropical Infectious Diseases: Principles, Pathogens and Practice, CHAPTER 75, 504-510 http://www.phac-aspc.gc.ca/publicat/ccdr-rmtc/09vol35/acs-dcc-2/index-eng.php Copyright © 2011 © 2011, Elsevier Inc. All rights reserved . SEVERAL FACTORS LIKELY CONTRIBUTE TO PROGRESSION TO DHF/DSS  Strain virulence  Host genetic factors  Antibody-dependent enhancement  © 2007 Nature Publishing Group Whitehead, S. S. et al. Prospects for a dengue virus vaccine. Nature Reviews Microbiology 5,518–528 (2007). All rights reserved. Front. Immunol., 06 July 2022 Sec. Viral Immunology Volume 13 - 2022 | https://doi.org/10.3389/fimmu.2022.889196 LABORATORY TESTING FOR DENGUE VIRUS IS PERFORMED IN CONJUNCTION WITH CLINICAL DIAGNOSIS NS1 detection Virus isolation RNA detection Viremia IgM primary IgM secondary IgG secondary IgG primary 0 7 14 90 Onset of symptoms (days) Modified from: Dengue: Guidelines for Diagnosis, Treatment, Prevention and Control: New Edition. Geneva: World Health Organization; 2009. THE TOURNIQUET TEST, A MEASURE OF CAPILLARY FRAGILITY, MAY BE USED TO CLINICALLY DIAGNOSE DENGUE  Not diagnostic of dengue by itself  Positive in up to 50% of patients with classic dengue  Almost always positive in severe dengue How To Do a Tourniquet Test 1. Take the patient's blood pressure and record it, for example, 100/70. 2. Inflate the cuff to a point midway between SBP and DBP, and maintain for 5 minutes, (100 + 70) ÷ 2 = 85 mm Hg 3. Reduce and wait 2 minutes. 4. Count petechiae below antecubital fossa. 1. A positive test is 10 or more petechiae per 1 square inch. YELLOW FEVER: A DEADLY BUT PREVENTABLE MOSQUITO-BORNE DISEASE Annu Rev Entomol. 2007. 52:209-29 CLINICAL PROGRESSION OF YELLOW FEVER Pathognomonic triad ZIKA VIRUS USUALLY CAUSES A MILD SELF-LIMITING INFECTION IN HEALTHY ADULTS  A subset of adult Zika patients present with Guillain-Barré syndrome (GBS) Most common symptoms in adults  Fever  Rash  Arthralgia  Conjunctivitis  Myalgia  Headache Most people recover within a week Can be sexually transmitted  Results in muscle weakness leading to paralysis  Rarely fatal ZIKA VIRUS INFECTION AFFECTS FETAL BRAIN DEVELOPMENT  ~5% of infections during pregnancy result in birth defects; <0.5% associated with pregnancy loss  Zika virus infects human neural stem cells and attenuates their growth in vitro https://www.sciencenews.org/article/microcephaly-cases-surge-colombia-following-rise-zikainfections LIMITED OPTIONS FOR TREATING FLAVIVIRUS INFECTIONS; PREVENTION IS KEY  Primary treatment is supportive care  Ribavirin is not effective  Vector management is critical to controlling the spread of infection  The Yellow Fever 17D vaccine is available for the prevention of Yellow Fever  Live, attenuated virus  Recommended for all individuals aged 9 months or older living in endemic regions  Required for travelers to certain countries  Recommended for travelers to areas of risk  Rare adverse reactions include encephalitis or disease resembling wild-type YF A DENGUE VACCINE IS AVAILABLE FOR SOME PEOPLE  CDC recommends dengue vaccination for children 9 through 16 years old, but only when they have been previously infected with dengue and living in areas where dengue is common.  Dengvaxia requires three doses and can prevent dengue illness, hospitalization, and severe dengue from all four dengue viruses.  This previous infection should be confirmed by laboratory testing.  This vaccine is different from other vaccines in that it is only recommended for people who have already been infected with dengue virus. The reason is that children without previous dengue infection are at increased risk for severe dengue disease and hospitalization if they get dengue after they are vaccinated with Dengvaxia. https://www.cdc.gov/vaccines/vpd/dengue/public/index.html CHIKUNGUNYA VIRUS IS AN ALPHAVIRUS (TOGAVIRIDAE)—SIMILAR TO FLAVIVIRUSES • Positive sense, single stranded RNA genome • Icosohedral capsid • Genome encodes early and late proteins, unlike flaviviruses • Envelope is wrapped tightly with the capsid • Enters the cell by receptor mediated endocytosis • Genome is translated in the cytoplasm in early and late phases • Non-structural proteins are produced first, producing large amounts of viral mRNA so that large amounts of structural proteins can be produced • Virus assembles at the plasma membrane and buds from the cell CHIKUNGUNYA VIRUS OVERLAPS WITH DENGUE IN DISTRIBUTION AND CLINICAL PRESENTATION • • • Associated with severe arthritis or arthalgia Currently, there are no specific treatments or vaccines for Chikungunya virus infection People should prevent mosquito bites during the first week of their illness to prevent further spread Flulike/ Systemic Encephalitis Hepatitis Hemorrhage Shock Dengue + — + + + Yellow fever + — + + + Zika + — — — — St. Louis encephalitis + + — — — West Nile encephalitis + + — — — Japanese encephalitis + + — — — Chikungunya + — — — — Eastern equine encephalitis + + — — —