（体外膜肺ECMO课件）-Bunyaviridae.ppt

1、BunyaviridaeClayton M.JohnstonBunyaviridae Largest family of mammal affecting viruses(250 viruses)Arthropod-or rodent-borne vectors Most are amplified in vertebrate hostsBunyaviridaeGenusDisease(s)BunyavirusLaCrosse encephalitisPhlebovirus Rift Valley FeverNairovirusCrimean-Congo Hemorrhagic FeverTo

2、spovirusPlant VirusHantavirusHemorrhagic Fever with Renal SyndromeHantavirus Pulmonary SyndromeStructure Virion Structure Genomic Structure Structural ProteinsVirion Structure Spherical 80-120 nm diameter Enveloped Helical nucleocapsid NO matrix proteinGenomic Structure(-)sense Linear ssRNA Three se

3、gments:Large(L)codes for viral polymerase Medium(M)codes for G1 and G2 glycoproteins Small(S)codes for nucleocapsidStructural Proteins Membrane Glycoproteins Nucleocapsid Protein Viral PolymeraseStructural ProteinsMembrane glycoproteins (G1 and G2)Nucleocapsid proteins(N)Polymerase(L)Membrane Glycop

4、roteins G1 and G2 Integral membrane proteins Important in cell entry and pathogenesisNucleocapsid Protein Complexes with genomic vRNA in virus,as well as with cRNA after infection,but not with mRNA Necessary for virus replication and packagingViral Polymerase RNA-dependent RNA polymerase Complexed w

5、ith ribonucleocapsid in virion Endonuclease activity to cleave host mRNA Transcriptase activity for making cRNA and mRNA from vRNA Helicase activity to unwind vRNA during transcriptionViral Replication Receptor mediated endocytosis Occurs in cytoplasm Budding at Golgi apparatus or cell membraneHanta

6、virus Replication Cycle Attachment Entry and Uncoating Primary Transcription Translation Genome Replication Secondary Transcription Virion Assembly Virion ReleaseAttachment Viral G1 and G2 glycoproteins interact with cell surface receptors Pathogenic hantavirus bind 3 integrins Non-pathogenic hantav

7、iruses bind 1 receptorsEntry and Uncoating Virus particles bound to integrin receptors are taken in by receptor mediated endocytosis Newly formed vesicles are acidified Acidic environment changes confirmation of G1 and G2 glycoproteins Viral and cell membranes fuse Genomic material and polymerase ar

8、e released into cytoplasmAttachment and EntryPrimary Transcription Transcription of negative sense vRNA to mRNA Viral polymerase transcribes nucleoprotein-coated vRNA Capped oligonucleotides from cells own mRNA are used to prime transcription(similar to Influenza virus)Translation L and S segments o

9、f mRNA are translated on free ribosomes in cytoplasm M segment mRNA is translated on ER-bound ribosomesTranslationGenome Replication vRNA is used as a template by viral polymerase to make cRNA cRNA is used as a template to make more negative sense strands of vRNASecondary Transcription Extra vRNA sy

10、nthesized during replication is used as template to make mRNA Since more template is present after vRNA is replicated,more mRNA can be transcribed,and more viral proteins can be made Persistent infectionVirion Assembly Membrane-bound G1 and G2 peptides are transported to Golgi apparatus and carbohyd

11、rates are attached by N-linked glycosylation vRNA complexes with N nucleocapsid protein,forms looped panhandle structure,and complexes with polymeraseVirion AssemblyVirion ReleaseTwo Mechanisms Nucleocapsid complexes bud into the Golgi membrane with G1 and G2 embedded Virion particle is formed insid

12、e Golgi apparatus Virions are transported to cell membrane by vesicles and released by exocytosis G1 and G2 embed into cell membrane through Golgi vesicles Virions bud from cell membrane,not through Golgi apparatusAttachmentEntryUncoatingTranscriptionTranslationReplicationAssemblyReleaseLaCrosse Enc

13、ephalatisBunyavirus Mostly infects children younger than 16 Ades mosquitoes are the common vector Squirrels and chipmunks are the amplifying host Most common bunyavirus infection in the United StatesLaCrosse EncephalatisBunyavirus Targets the brain Symptoms may include:Fever Convulsions Drowsiness F

14、ocal neurological signsRift Valley FeverPhlebovirus Most spread by sandfly or Ades species of mosquitoes Causes abortion in livestock Highly infectious by aerosolized blood Distribution follows that of the host vectors Immunization of livestock is the most effective way to control and prevent the di

15、seaseRift Valley FeverPhlebovirus Febrile disease in humans Targets the liver Symptoms often include:Fever Encephalitis Retinal vasculitis(which may lead to blindness)Rift Valley FeverDistribution MapCrimean-Congo Hemorrhagic FeverNairovirus Transmitted by ticks Appears in the Middle East and Africa

16、 Targets the liver and vascular endothelium Symptoms include:Headache Pain in limbs Often bleeding from many orificesCrimean-Congo Hemorrhagic FeverNairovirusHantavirus Enveloped ssRNA Virions 98 nm in diameter Genome consists of three RNA segmentsTransmissionVectors Transmitted via aerosolized rode

17、nt urine,feces,and saliva Deer mouse(Peromyscus maniculatus)Cotton rat(Sigmodon hispidus)White-footed mouse(Peromyscus leucopus)Striped field mours(Apodemus agrarius)Bank vole(Clethrionomys glareolus)Rat(Rattus)Hemorrhagic Fever with Renal SyndromeHantavirus Liver and vascular enothelium are targete

18、d Symptoms include:Hemorrhage Acute renal failure Fever Over 15%mortality rateHantavirus Pulmonary SyndromeHantavirus Lungs are targeted Symptoms include Fever Acute respiratory distress Over 50%mortality rate Shock and cardiac complications often contribute to deathPrevention and Control Vaccines H

19、ygiene Vector ControlVaccines E.coli expressed truncated nucleocapsid as an immunogen Naked DNA Recombinant non-pathogenic virus Rodent brain-derived Cell culture derived Inactivated virus being tried out in ChinaHygiene Prevent aerosolization of virus from roden excrement Dampen surfaces with bleac

20、h before cleaning Control rodents and human contact with rodentsHost Defenses and Immune Response Interferon is produced Humor antibody has been shown to be related to the disappearance of virus from blood Cytotoxic T-cells attack infected host cells Inflammatory responseTreatment Early aggressive i

21、ntensive care Early use of inotropic agents(Dobutamine)Early ventilation Careful monitoring:Oxygenation Fluid balance Blood pressureTreatment General care,alleviation of symptoms Ribavirin(Hemorrhagic Fever with Renal Syndrome)ECMO(Hantavirus Pulmonary Syndrome)Ribavirin Administered intravenously S

22、hown to be effective against Hemorrhagic Fever with Renal Syndrome Not shown to be effective against Hantavirus Pulmonary Syndrome causing strainsExtra Corporeal Membrane Oxygenation(ECMO)Removes blood from the body and artificially removes CO2 and adds O2 Costly DifficultECMOLaboratory Diagnosis Se

23、rology(ELISE for IgM)Immunohistochemistry Reverse transcription and polymerase chain reaction(RT-PCR)Virus isolation Direct detection of antigen in blood and urine Immunofluorescent test for antibodiesProblems Diagnosing Hantavirus Symptoms often confused with influenza Common signs of upper respira

24、tory disease such as sore throat,sinusitis,and ear pain not usually present Abdominal pain often misinterpreted as appendicitis Many doctors outside endemic regions fail to recognize or have sufficient testingFriday,March 26,2004PARKS AND PEOPLE Glacier National ParkDeath of Jerry ONealThe employees

25、 of Glacier National Park are deeply saddened to learn of the untimely passing of Deputy Superintendent Jerry ONeal.ONeal died early yesterday morning at a Kalispell,Mont.,hospital following a brief illness.ONeal,61,came down with an unknown illness last week and had undergone blood work and other d

26、iagnostic tests over the past few days.He was admitted to the Kalispell Regional Medical Center on Wednesday and died at 5:30 a.m.Thursday.Friday,April 2,2004OPERATIONS NOTE Public HealthHantavirus UpdateIn view of the untimely death of Glacier National Park Deputy Superintendent Jerry ONeal on Marc

27、h 25th from hantavirus pulmonary syndrome,we are issuing the following precautions and annual reminders.Hantavirus pulmonary syndrome(HPS)is a viral disease transmitted to humans primarily through the inhalation of airborne dusts laden with the virus from infected rodent droppings(urine and saliva m

28、ay also be sources of infection).Although hantaviruses have been a threat to human health worldwide for at least 50 years,HPS was first recognized in the United States in 1993 around the Four Corners area of the Southwest.Since then it has since been identified throughout the United States.Although rare,HPS is potentially deadly mortality rates between 40 and 50%are common.