Ebola summary report

School of Biotechnology, International University-HCMC Department: BioTechnology GROUP PRESENTATION_MICROBIOLOGY CLASS Abstract Ebola virus (EBOV) is a member of the Filoviridae virus family along with Marburg virus (MARV) Together they are commonly known as filoviruses EBOV is a virulent pathogen that causes fatal hemorraghic fever in humans and nonhuman primates A large majority of patients infected with EBOV, and who are not properly treated, fall ill within 2-20 days after exposure, with 50-90% death rate There has been greater than 2,300 reported cases of hemmorraghic fever caused by filoviruses, EBOV and MARV The actual number of cases is expected to be even higher as it is suspected that many cases go unreported in rural African villages The EBOV virus has infected many parts of the world, but the majority of the infectious outbreaks occur in central Africa Outline: 1) Introduction 2) Ebola Classification and its system .4 - Classification - Structure and Genome of Ebola - Replication - Immune System evasion .9 - Pathophysiology - Transmission and reservoir 10 3) Symptoms of Ebola disease 12 4) Prevention and Treatment 12 5) References 1) Introduction about Ebola Virus: The Ebola virus belongs to a family of viruses called Filoviridae There are five species of the virus: Bundibugyo (BDBV), Sudan (SUDV), Reston (RESTV), Zaire (EBOV), Tai Forest (TAFV) ebolavirus Ebola first appeared in 1976 in simultaneous outbreaks, in Nzara, Sudan, and in Yambuku, Democratic Republic of Congo Species of fruit bats are considered to be the natural host of the Ebola virus 2) Ebola Classification and its system: Classification: Genus Ebolavirus is of members of the Filoviridae family (filovirus), along with genus Marburg virus and genus Cueva virus Group: Group V (-)ssRNA Order: Mononegavirales Family: Filoviridae Genus: Ebolavirus Structure and Genome of Ebola: Structure An electron micrograph of Ebola virus Ebola is a filamentous virus with a single-stranded RNA genome with an unusual, variable-length, branched morphology The helical capsid is enclosed inside a membrane The tubular Ebola virions are generally 80 nm in diameter and 800 nm long In the center of the particle is the viral nucleocapsid which consists of the helical ssRNA genome wrapped about the NP, VP35, VP30 and L proteins This structure is then surrounded by an outer viral envelope derived from the host cell membrane that is studded with 10 nm long viral glycoprotein (GP) spikes Between the capsid and nvelope are viral proteins VP40 and VP24 Viral proteins VP40 and VP24 are located between the envelope and the nucleocapsid , in the matrix space At the center of the virion structure is the nucleocapsid, which is composed of a series of viral proteins attached to an 18–19 kb linear, negative-sense RNA without 3′-polyadenylation or 5′-capping; the RNA is helically wound and complexed with the NP, VP35, VP30, and L proteins; this helix has a diameter of 80 nm and contains a central channel of 20–30 nm in diameter Caps and polyadenylated tails are added during creation of the mRNA This envelope GP spike is expressed at the cell surface, and is incorporated into the virion to drive viral attachment and membrane fusion It has also been shown as the crucial factor for Ebola virus pathogenicity GP is actually post-translationally cleaved by the proprotein convertase furin to yield disulphide-linked GP1 and GP2 subunits GP1 allows for attachment to host cells, while GP2 mediates fusion of viral and host membranes This protein assembles as a trimer of heterodimers on the viral envelope, and ultimately undergoes an irreversible conformation change to merge the two membranes Genome Each virion contains one molecule of linear, single-stranded, negative-sense RNA, 18,959 to 18,961 nucleotides in length The 3′ terminus is not polyadenylated and the 5′ end is not capped The EBOV genome is approximately 19 kb in length It encodes seven structural proteins: - Nucleoprotein (NP) - Polymerase cofactor (VP35), (VP40) - GP - Transcription activator (VP30), (VP24) - RNA polymerase (L) This viral genome codes for seven structural proteins and one non-structural protein The gene order is 3′ – leader – NP – VP35 – VP40 – GP/sGP – VP30 – VP24 – L – trailer – 5′; with the leader and trailer being non-transcribed regions, which carry important signals to control transcription, replication, and packaging of the viral genomes into new virions Replication Ebola not replicate through any type of cell division; rather, they use a combination of host- and virally encoded enzymes, alongside host cell structures, to produce multiple copies of themselves These then self-assemble into viral macromolecular structures in the host cell The virus begins its attack by attaching to host receptors through the glycoprotein (GP) surface peplomer and then engulged by endocytosis in the host cell Ebola virion envelope and cellular membrane of host fuses together and the virus nucleocapsid is release Virus uncoats and nucleocapsid is transcribed onto positive stranded mRNA into viral proteins Glycosylation occurs in which viral proteins attach to glycan and glycoprotein precursors are cleaved into glycoprotein and 2, which assemble to form heterodimers In the meantime, a negative stranded RNA strand is synthesized to be used as template to create positive single stranded RNA Heterodimers multiply to form trimmers that will form the surface peplomers of the emerging of the Ebola cells New viral copies are made form the negative stranded RNA strand and the trimers make their way to the cell membrane Formation of the viral envelope and nucleocapsid occur when the trimers and new genomes gather around the edges of the host cell in preparation for building Newly form Ebola viruses bud from the host cell, gaining the cell membrane Mature progeny are free to infect the other cell Immune system evasion Infectious agents can evade the destruction of the immune system by changing the antigen This important cause can help those agents against the fence of antibodies on the surface Three modes of antigenic variation: + diverse variants + using neutralizing antibodies + rearranging genomes Viruses often distract their presence on the immune system Simultaneously, when entering host cells, they synthesize their own proteins, and reproduce quickly lead to disease Ebola set genome and the proteins into the host cell The cell will produce many copies with extremely fast speed Each Ebola virus contains particularly large number of glycoproteins that enhance the ability to infect any accessible cell, help the virus attach to host cells and conduct transgenic Ebola is particularly adept at partially protecting their host cells from the immune system, by a largely unknown mechanism One theory is that the Ebola virus has released a protein that disables the immune system response The human immune system can normally recognize infected cells and target them for destruction ⇒ If scientists can elucidate the molecular-level mechanism of how Ebola-infected cells evade the immune system, it may contribute to a treatment for the Ebola virus Pathophysiology EBOV replicates very in many cells, producing large amounts of virus in monocytes, macrophages, dendritic cells and other cells including liver cells, fibroblasts, and adrenal gland cells Viral replication triggers the release of high levels of inflammatory chemical signals and leads to a septic state Endothelial cells (cells lining the inside of blood vessels), liver cells, and several types of immune cells such as macrophages, monocytes, and dendritic cells are the main targets of infection The immune cells carry the virus to nearby lymph nodes where further reproduction of the virus takes place From there, the virus can enter the bloodstream and lymphatic system and spread throughout the body Macrophages are the first cells infected with the virus, and this infection results in programmed cell death Other types of white blood cells, such as lymphocytes, also undergo programmed cell death leading to a low concentration of lymphocytes in the blood This contributes to the weakened immune response Endothelial cells may be infected within days after exposure to the virus The breakdown of endothelial cells leading to blood vessel injury can be attributed to EBOV glycoproteins, which reduces the availability of specific integrins responsible for cell adhesion to the intercellular structure and causes liver damage, leading to improper clotting Bleeding will cause swelling and shock The bleeding is caused by increased activation of the extrinsic pathway of the coagulation cascade due to excessive tissue factor production by macrophages and monocytes After infection, a secreted glycoprotein is synthesized EBOV replication overwhelms protein synthesis of infected cells and the host immune defenses The GP forms a trimeric complex, which tethers the virus to the endothelial cells The sGP forms a dimeric protein that interferes with the signaling of neutrophils, another type of white blood cell, which enables the virus to evade the immune system by inhibiting early steps of neutrophil activation The presence of viral particles and the cell damage resulting from viruses budding out of the cell causes the release of chemical signals (such as TNF-α, IL-6 and IL-8), which are molecular signals for fever and inflammation Transmission and Reservoir Reservoir Because the natural reservoir of Ebola virus has not yet been identified, it is not known how the virus first appears in a human at the start of an outbreak However, researchers in Africa believe that the first patient becomes infected through contact with an infected animal, such as a fruit bat or nonhuman primate Transmission Because the natural reservoir of Ebola virus has not yet been identified, it is not known how the virus first appears in a human at the start of an outbreak However, researchers believe that the first patient becomes infected through contact with an infected animal, such as a fruit bat or nonhuman primate Infected bats are thought to transmit the disease to humans, or indirectly through other animals which are hunted for their meat Possible route: * Close contact with the blood, secretions, organs or other bodily fluids of infected or dead animals * Consumption of infected bushmeat * Touching objects that have come in contact with the virus ……………………… Transmission and reservoir It is thought that fruit bats of the Pteropodidae family are natural Ebola virus hosts These viruses naturally occur in bats and probably not cause severe disease in these animals Because the Ebola virus and the bat have been evolving together - the Ebola virus infecting the bat and the bat's immune system fighting the virus - for hundreds if not thousands of years, they have reached a sort of 10 evolutionary equilibrium where the Ebola virus doesn't make the bat too sick thanks to the bats immune system and the bat transmits the Ebola virus to other bats during its life When an infection occurs in humans, the virus can be spread to others through direct contact (through broken skin or mucous membranes in, for example, the eyes, nose, or mouth) with Blood or body fluids (including but not limited to urine, saliva, sweat, feces, vomit, breast milk, and semen) of a person who is sick with or has died from Ebola Objects (like needles and syringes) that have been contaminated with body fluids from a person who is sick with Ebola or the body of a person who has died from Ebola Infected fruit bats or primates (apes and monkeys), and Possibly from contact with semen from a man who has recovered from Ebola (for example, by having oral, vaginal, or anal sex) Person-to-person transmission follows and can lead to large numbers of affected people Ebola is not spread through the air, by water, or in general, by food However, in Africa, Ebola may be spread as a result of handling bushmeat (wild animals hunted for food) and contact with infected bats There is no evidence that mosquitoes or other insects can transmit Ebola virus Only a few species of mammals (e.g., humans, bats, monkeys, and apes) have shown the ability to become infected with and spread Ebola virus 11 3)Symptoms of Ebola disease Symptoms: Symptoms of Ebola include: • Fever • Severe headache • Muscle pain • Weakness • Fatigue • Diarrhea • Vomiting • Abdominal (stomach) pain • Unexplained hemorrhage (bleeding or bruising) Symptoms may appear anywhere from to 21 days after exposure to Ebola, but the average is to 10 days Recovery from Ebola depends on good supportive clinical care and the patient’s immune response People who recover from Ebola infection develop antibodies that last for at least 10 years 4) Prevention and Treatment Prevention Individuals with suspected or confirmed Ebola virus disease need to be isolated and excluded from childcare, preschool, school and work until cleared to return by a doctor  Health care workers who care for a patient with suspected or confirmed Ebola virus disease should use hand hygiene and appropriate personal protective equipment  For at least several months after recovery and until advised otherwise by a doctor, males who have had Ebola virus disease should use a condom when engaging in sexual intercourse  Those who visit an area where Ebola virus disease occurs should not eat raw or undercooked ‘bush meat’ including ape, monkey or bat  People should not have contact (or eat) with blood, meat or body fluids of animals which show signs of Ebola virus disease  12 Until now, there is no FDA-approved vaccine available for Ebola Therefore, if you travel to or are in an area affected by an Ebola outbreak, make sure to the following: Practice careful hygiene For example, wash your hands with soap and water or an • alcohol-based hand sanitizer and avoid contact with blood and body fluids (such as urine, feces, saliva, sweat, urine, vomit, breast milk, semen, and vaginal fluids) Do not handle items that may have come in contact with an infected person’s • blood or body fluids (such as clothes, bedding, needles, and medical equipment) Avoid funeral or burial rituals that require handling the body of someone who has • died from Ebola Avoid contact with bats and nonhuman primates or blood, fluids, and raw meat • prepared from these animals Avoid facilities in West Africa where Ebola patients are being treated The U.S • embassy or consulate is often able to provide advice on facilities After you return, monitor your health for 21 days and seek medical care • immediately if you develop symptoms of Ebola Healthcare workers who may be exposed to people with Ebola should follow these steps: • Wear appropriate personal protective equipment (PPE) • Practice proper infection control and sterilization measures • Isolate patients with Ebola from other patients • Avoid direct, unprotected contact with the bodies of people who have died from Ebola • Notify health officials if you have had direct contact with the blood or body fluids, such as but not limited to, feces, saliva, urine, vomit, and semen of a person who is sick with Ebola The virus can enter the body through broken skin or unprotected mucous membranes in, for example, the eyes, nose, or mouth Treatment: Experimental vaccines and treatments for Ebola are under development, but they 13 have not yet been fully tested for safety or effectiveness Today, no vaccine is currently available for humans Currently, two vaccine are entering efficacy trials in humans: ChAd3-ZEBOV and rVSV-ZEBOV Recovery from Ebola depends on good supportive care and the patient’s immune response People who recover from Ebola infection develop antibodies that last for at least 10 years, possibly longer It is not known if people who recover are immune for life or if they can become infected with a different species of Ebola Some people who have recovered from Ebola have developed long-term complications, such as joint and vision problems 5) References: http://en.wikipedia.org/wiki/Ebola_virus http://www.microbiologytext.com/ http://www.csie.ntu.edu.tw/~kmchao/bioinformatics14spr/slides/Ebola_slides.pptx http://www.cdc.gov/vhf/ebola/ http://viralzone.expasy.org/all_by_species/5016.html http://www.nasw.org/users/mslong/2010/2010_09/Ebola.htm 14