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Virology

QuestionAnswer
What is a virus? Obligate intracellular parasite that infects all forms of life.
Before a virus penetrates it must attach to the host cell, how does it do this? Proteins spikes have ligands which bind to receptors on the host cell. This may be a specific interaction i.e. some viruses may only be able to infect respiratory cells.
How do unenveloped viruses enter cells? Fusion with membrane
How do enveloped viruses enter cells? Binding to receptor initiates endocytosis
How do viruses replicate once inside the host cell? Use host resources to replicate and produce more protein coats. DNA replication occurs in the nucleus, RNA replication occurs in the cytoplasm. Ribosomes are used to synthesize new protein coats. Process can be mediated by viral enzymes.
Describe the two methods by which viruses are released from the host cell. Lysis: viruses accumulate until host cell bursts, host cell is killed in the process. Budding: virus in released by exocytosis, virus takes part of lipid membrane with it to form new envelope. Host cell is not harmed.
Describe the structure of a virus. What forms can it take? NA genome either DNA or RNA, surrounded by protein coat with protein spikes. Lipid envelope may surround. Naked icosahedral capsid Enveloped icosahedral capsid Naked helical nucleocapsid Enveloped helical nucelocapsid
What is the Baltimore Classification of Viruses based on? Properties of genome
What kind of genome does a class I virus have? Examples? dsDNA. Adeno, Herpes, Pox.
What kind of genome does a class II virus have? Examples? ssDNA. Parvo.
What kind of genome does a class III virus have? Examples? dsRNA. Reo.
What kind of genome does a class IV virus have? Examples? Positive sense ssRNA. Ortho, Rhabdo, Flu, Ebola.
What kind of genome does a class V virus have? Examples? Negative sense ssRNA. Pico, Toga.
What kind of genome does a class VI virus have? Examples? ssRNA retro. Retro.
What kind of genome does a class VII virus have? Examples? dsRNA reverse. Hep.
What are the four types of virus infection patterns? Acute, Persistent, Latent Reactivating, Slow
How many types of Herpes Virus are there? Name them. 8. HSV1 and 2. VSV. Epstein Barr. Cytomegalovirus. HHV6, 7, 8.
What Class of virus is herpes? Class I- dsDNA
Is the herpes virus enveloped? yes
What is the incubation period associated with herpes? 5-8days
Describe Herpes Simplex Virus latency? Primary infection causes mild pharyngealitis and fever. When exposed to fever, sunlight, mestruation, it activates the virus in the spinal neurone and causes a cold sore.
Describe Varicella Zoster Virus latency? Primary infection causes chicken pox. When exposed age, irradiation, or local injury (depressed immune system) it activates the virus in the spinal neurone and causes Shingles.
Give examples of viruses for which there is no vaccine? HIV, rotavirus, herpes
Describe the immune response which occurs to fight of viral infection? cytotoxic T cell recognises and causes apoptosis of the infected cell. neutralising Ig can stop binding of virus.
What is viral persistance? Viruses which stay active like HIV and HPV. Viruses which may reactivate like Herpes Simplex and VSV.
What are the difficulties associated with antiviral drugs? Few biochemical pathways are unique to viruses, viruses mutate, some viruses cause v similar diseases but have very different replication modes, by the time th host is symptomatic it is too late to use chemotherapy.
What are the symptoms of Influenza? headache, fever, tiredness, achy joints, runny nose, sore throat, aches, cough, vomiting
How is Influenza transmitted? Respiratory/Saliva
What class of virus is influenza? What is its incubation period? Class 5: negative sense ssRNA 1-2 days.
When did the Spanish Flu outbreak happen? How many people did it kill? 1918. 50 000 000
What was the first Flu pandemic to arise in 40 years (2009)? What strain of flu caused it? H1N1, Influenza A. Swine Flu.
How many strands of RNA does Influenza A contain? How many proteins does it code for? 8 strands, 10 proteins
What are the proteins encoded by Influenza A? PB2, PB1, PA, HA (hemagglutinin), NP (nucleoprotein), NA (neuraminidase) M2(ion channel), NS1, NS2 (non struct proteins)
How are Influenza A strains/subtypes classified? According to two structural variants of the two surface proteins Hemagglutinin (1-15) and Nueraminidase (N1-9)
What is the target for drugs rimantadine and amantadine? Ion channel protein (M2)
By what process does Influenza A mutate? Antigenic Drift
What is antigenic drift? What does it mean for human immunity? Existing antigens are suddenly altered when two or more strains combine. Humans may partial but not complete immunity or no immunity at all.
How did H1N1 come about? antigenic drift in mexican pigs. Mix between avian, porcine and human flu. Meant that humans had some antigens.
What is hemagglutinin and what is it responsible for? Influenza hemagglutinin is a glycoprotein found on the surface of influenza viruses. It is responsible for binding the virus to cells with sialic acid on the membranes
How does vaccination again viruses work? Improves immunity to disease by presenting a small amount of agent that resembles the virus to stimulate the immune system to recognize the agent as foreign and destroy it. The body then has memory of the antigen so its easier to kill on next exposure.
What does influenza neuraminidase do? enables the virus to be released from the host cell. Neuraminidases are enzymes that cleave sialic acid groups from glycoproteins.
What is Oseltamivir? What does it do? Antiviral drug. Bind NA (similar struct to scialic acid) to stop cleavage from host cell. Symptom alleviation in half a day to one day. (Tamiflu)
What is Zanamivir? What does it do? NA inhibitor. treatment and prophylaxis of flu. Relenza. Binds active site of NA, so virus cant cleave.
How does influenza cause symptoms? Huge release of pro-inflammatory cytokines and chemokines (IFN AND TNF) produced by infected cells. Cytokine storm proposed for lethality of 1918 pandemic.
What developments facilitate virus spread? Air travel, global trade, urbanization, pop growth, climate change.
When did HIV/AIDS pandemic start? 1981.
What does HIV do? destroys and/or impairs cells of immune cells (CD4), progressively destroys bodies ability to fight infection and some cancers.
What does HIV stand for? Human Immunodeficiency Virus
What does AIDS stand for? Acquired Immunodeficiency Syndrome
Describe AIDS in patients older than 13 years. Presence of one of 25 conditions indicate immunosupression. HIV infection with CD4+ T cell count less than 200cells/cubic ml of blood. younger than 13- same but lymphoid interstital pneumoitits and recurrent bacterial infections also indicated.
How many deaths caused by AIDS since 1981? more than 50 million
How is HIV transmitted? by body fluids. e.g. sex, drugs, transfusions.
What class of virus is HIV? Class VI: ssRNA (retrovirus family) (lentivirus)
What is the HIV genome enclosed by? conical capsid composed of viral protein p24
How many copies of the genome does HIV contain? How many genes? 2 copies. 9 genes.
What virion proteins does the HIV capsid contain? reverse transcriptase, protease, integrase
What proteins allow the HIV virus to attach to cells? glycoprotein 120 (bud) and glycoprotein 41 (stem)
How do HIV viruses exit the cell? Budding
How does HIV RNA replication occur in the host cell? In the cytoplasm, viral ssRNA is reverse transcribed into dsRNA- this is v error prone causing mutations which makes drug treatment v. difficult.
Describe how the HIV virus enters the cell? binding of gp120 (adsoprtion) to CD4 and CCR5. CXCR4 . Interaction of trireceptorsmeric envelope complex followed by fusion (med. gp41) with cell membrane and release of capsid into cell. HIV RNA and enzymes released (uncoating).
Describe the stages of HIV infection. Early incub- 2-4 weeks asymptomatic. Acute- 28days, fever rash, esophageal sores etc. Latency- asymptomatic 2weeks-20years. AIDS- opportunistic infections, progressive decrease of CD4 and increased viral load. Death in 1 year after the onset of AIDS.
Give some examples of antiviral compounds which target cell attachment, fusion and entry of the HIV virus? CD4 derivatives, chemokine analogues, plant lectins, bicyclams
Drugs which target the reverse transcription of the HIV genome? Nucleoside RTA inhibitors e.g. zidovadline, didanosine, zalcitabine , lamivudine
What type of drugs inhibit HIV virus integration? Integrase inhibitors
What do TAT inhibitors block? Transcription and Post-transcriptional processing of the virus genome
What do protease inhibitors do? Block Packaging and Budding (also nucleocaspid inhibitors)
Give examples of Protease inhibitors. Ritonavir, atazanavir, nelfinavir, saquinavir
What is the boosted Protease Inhibitor Concept? Ritonavir is not used because major side effect, but strongly inhibits CYP45O and the metabolism of other PI's, which allows for lower doses of other PI's.
What is a zoonotic virus? a disease that can be transmitted from animals to people or, more specifically, a disease that normally exists in animals but that can infect humans.
Example of a zoonotic virus? Ebola (bats most likely)
What class of virus is Ebola? Class V: negative sense, ssRNA
How is Ebola transmitted? blood, fluids, excrement from infected patients. Direct contact with fluids or with corpse, sharps injury, Indirect fluid contact or contact with fluids of infected animal
How many proteins from Ebola? 7
How many species of Ebola? 5
Where is Ebola most prevalent? West Africa
What are the proteins produced by Ebola? Ribonucleocapsids: NP, VP35, VP30, Polymerase L Matrix: VP40, VP24 Membrane proteins: glycoproteins
Describe Ebola Virus Entry and Replication in host cells? Surface spikes recognise and bind surface receptors of host, virus enter via endocytosis, release of nucleocapsid into cytoplasm, transcription on viral RNA into polyadenylated monocistronic mRNA. Release by budding. Host cell dies.
How is EVD diagnosed? Real Time PCR, most sensitive than ELISA. IgM 10 days after, IgG 20 days after. Critical info: date of infection.
Describe the clinical features of Ebola? Non-specific early symptoms. Hemorrhagic disease- hypovolemic shock, death. Non fatal- 6-11 days improvement. Fatal-more severe early symptoms, fatality is 70% in rural africa. IV electrolytes may increase survival rate
How does Ebola affect the immune system? Infects mononuclear phagocytes- fail early Tcell act, disrupts antigen trafficking and cytokines, damage to lymph. VP35 is a type 1 IFN antagonist, enhances replication ability of virus.
Describe the drug therapies being investigated for EDV? no approved prophylaxis od treatent. ZMapp- 3 chimeric human mouse monoclonal Igs. Tekmira- lpip nanoparticle. Favipiravir- oral RNA dependent RNA polymerase inhibitor.
Describe the two vaccines currently under investigation for EDV? chimp adenovirus with Ebola RNA gene inserted attenuated vesicular stomatitis viral Ebola gene
Created by: Laura Inglis