Viruses

What is a virus? (1)

Obligate intracellular parasites able to infect all living organisms (animals, plants, bacteria). Mature infectious particle of virus life cycle is virion

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What is a virus? (2)

Virions consists of a protein covering (capsid) surrounding a core containing the viral genome (either DNA or RNA). Some virions are covered by an outer lipoprotein envelope. Viruses lack any metabolism and rely on host cell metabolism to replicate

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What is a virus? (3)

Viruses don't exist/replicate outside a host cell

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What are bacteriophages?

Viruses with infect bacteria (must be specific)

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Describe the general characteristics of viruses

Viruses range from 25 nm (0.025 microns) for polio virus to smallpox at 300 nm (0.3 microns). Due to their small size, viruses are generally on visible using EM

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Describe features of culturing and identifying viruses (1)

Must be cultured in animal cells. Pathology studies in mammals. Identification from culture in chick embryo (inoculate different parts of the chick embryo depending on the type of virus e.g. influenza in amniotic cavity)

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Describe features of culturing and identifying viruses (2)

Identification from culture in chick embryo. Tissue/cell culture (e.g. growth in human fibroblasts). Serological tests (testing for specific antibodies). Molecular biology techniques (genome sequencing)

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Describe features of culturing and identifying viruses (3)

(Development of vaccines, new methods introduced in order to avoid use of chick embryos). Can use human cells for virus cultivation

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Describe features of virion morphologies (1)

Icosahedral viruses (20 faces) - naked icosahedral virus (nucleic acid in capsid) e.g. Rhinovirus. Enveloped icosahedral virus (nucleic acid, tegument, glycoprotein, capsid, envelope) e.g. Simplex virus

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Describe features of virion morphologies (2)

Helical viruses - naked helical virus (nucleic acid in capsid) e.g. Plant viruses (TMV). Enveloped helical viruses (nucleic acid, polymerase, nucleoprotein, matrix protein, glycoprotein, envelope) e.g. Ebola virus

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Describe features of complex viruses (1)

Viruses with morphologies other than icosahedral or helical are described as complex viruses. Poxviruses (Poxviridae) are complex dsDNA viruses which includes Molluscum contagiosum (MOCV)

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Describe features of complex viruses (2)

Double envelope structure is formed from host membranes such as Golgi apparatus and plasma membrane

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Describe features of capsid structure (1)

Viral capsid made up of repeating protein units (capsomeres, triangle-like structures) which self-assemble into icosahedral shape. Each capsomere consists of smaller sub-units called protomeres

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Describe features of capsid structure (2)

In helical viruses the protomeres are not symmetrically shaped and assemble into ribbon-like structures which fold into a helix

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Describe features of viral nucleic acids (1)

Viruses are broadly cla**ified primarily by the type of genomic nucleic acid they contain. DNA viruses may contain either double-stranded (ds) DNA or single stranded (**) DNA. RNA viruses may contain either dsRNA or **RNA

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Describe features of viral nucleic acids (2)

Single strands of nucleic acids in ssDNA and ssRNA viruses may be either coding (sense) strands or non-coding (anti-sense) strands

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Describe features of viral nucleic acids (3)

Retroviruses are RNA viruses which require reverse transcriptase to form DNA which is then incorporated into the host genome before replication takes place. Enzyme reverse transcriptase is carried as part of virion

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Describe the inactivation of viruses (1)

Alteration of functional parts of viruses (envelope, capsid, nucleic acid) via physical or chemical means leads to inactivation (viruses are not alive, cannot be killed)

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Describe the inactivation of viruses (2)

Enveloped viruses - solubilise envelope lipids by use of alcohols or detergents, inactivates virus. Capsid proteins - denatured by phenol containing disinfectants. Viral nucleic acid - damaged by exposure to UV radiation (no viral replication)

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Describe the inactivation of viruses (3)

Heat destroys all viral components equally well, viral inactivation can be achieved by autoclaving (120 degrees Celsius for 20 min) or by use of a sterilising oven (180 degrees Celsius for 60 min)

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Describe features of virus-host cell interactions (1)

Multiplication of virus and lysis of host cell (transmission). Elimination of virus, infection aborted with no particular cell damage (DICER cleavage of viral RNA). Cell is infected and survives unchanged but carries viral genome in latent state

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Describe features of virus-host cell interactions (2)

(integrated in genome e.g. HIV or HPV). Cell is infected and survives but in a transformed state (neoplasm). HIV existing within our own cells, remain dormant (HIV treatments - doesn't treat dormant forms). Some viruses associated with cancer

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Describe the attachment to host cells

Virions become attached to specific host cell receptors via protein/glycoprotein molecules on capsid or envelope. Host cell receptors are normal surface molecules involved in routine cell function

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What are the receptor molecules for the following viruses - influenza, rabies, HIV, Epstein-Barr, Vaccina (Pox virus), reovirus type 3 (infant gastric virus), rhinovirus (cold virus)? (1)

Influenza (haemagglutinin to sialic acid on glycoproteins of RBCs and mucous membranes). Rabies (ACh receptor). HIV (CD4 receptor on T cells). Epstein-Barr (C3d receptor on B cells). Vaccina (epidermal growth factor receptor)

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What are the receptor molecules for the following viruses - influenza, rabies, HIV, Epstein-Barr, Vaccina (Pox virus), reovirus type 3 (infant gastric virus), rhinovirus (cold virus)? (2)

Reovirus type 3 (beta-adrenergic hormone receptor). Rhinovirus (intercellular adhesion molecule 1 in nasal epithelium, CD54)

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Outline penetration and uncoating

Naked virus (injected into host cell with virus attached to the surface of the host cell). Enveloped virus (whole virus entering host cells with genetic material being injected into host cell)

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Describe features of viral replication (1)

Early genes generally code for viral polymerase enzymes. Late genes code for structural protein. DNA viruses generally replicate in the nucleus (except Poxviruses). RNA viruses mainly replicate in cytoplasm

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Describe features of viral replication (2)

dsDNA +/- (papo/adeno/herpes/pox viruses. ssRNA + (picorna/toga viruses). ssRNA+ to dsDNA (retroviruses). daRNA +/- (reoviruses). ssRNA- to RNA+ (paramyxoviruses, rhabdoviruses). ssDNA +/- to dsDNA +/- (parvoviruses)

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Describe features of virion assembly and release (1)

Naked viruses are assembled complete from nucleic acid and capsid proteins, in the cell cytoplasm; cell lysis occurs releasing virions.

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Describe features of virion assembly and release (2)

Enveloped virus proteins are incorporated into host cell membrane, capsid enclosed nucleic acid buds off at the plasma membrane, forming enveloped virion.

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Describe features of picornaviruses (1)

Naked ssRNA (+sense strand) viruses which replicate in host cell cytoplasm. Rhinovirus (common cold), enterovirus (GIT), hepatovirus (Hep A). Rhinovirus binds to CD54 receptors on respiratory epithelial cells

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Describe features of picornaviruses (2)

Receptor binding, entry, uncoating, translation, polyprotein processing, pro-apoptotic effects, shut off host cell translation/transcription, dsRNA (latency), viral replication complex (+/-strand synthesis, genome), packaging, cell lysis/viral egress

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Describe features of the influenza virus (1)

Types A/B/C (A - most virulent, only able to infect birds as well as mammals). Enveloped ssRNA virus with haemagglutinin and neuraminidase gp spikes. Envelope is linked with matrix protein (M1) and spanned by ion channel (M2)

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Describe features of the influenza virus (2)

Genome consists of 8 anti-sense ssRNAs with associated nucleoprotein and polymerase enzymes. Primary infection is of ciliated cells of URT. Self-limiting (after 3-7 days). Issue with virus mixing within populations

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Describe features of the influenza virus (3)

Endocytotic uptake facilitated by binding of HA spikes to sialic (N-acetyl neuramic) acid polysaccharide on cell surface

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Describe features of the influenza virus (4)

Ion channel M2 aids uncoating & release from endosome in response to low pH

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Describe features of the influenza virus (5)

Viral –RNA and polymerase translocate to the nucleus (5), where the viral RNA is transcribed and replicated. + RNA transcripts are translated by ribosomes in the cytosol

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Describe features of the influenza virus (6)

Virus buds from surface (coated with HA NA & M2 from golgi) with release aided by NA

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Describe features of the influenza virus - antigenic drifts

Results from mutations in HA & NA proteins causing minor changes in antigenicity. Antigenic shift results from co-infection of different strains in the same host causing major antigenic change → pandemic

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Describe features of the influenza virus - treatment

Amantadine blocks M2 ion channel preventing uncoating. Oseltamivir (Tamiflu) is a NA inhibitor (substrate analogue). Vaccines developed for emerging strains (monitoring influenza)

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Describe features of HHV (Human Herpes Viruses) (1)

Herpes Simplex Virus 1/2, varicella zoster virus (3), Epstein-Barr virus (4), cytomegalovirus (5). dsDNA enveloped virus (HHV 1-8). Causes life long latent infections. Reactivation of latent infection caused by stress, ageing immunosuppression etc

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Describe features of HHV (Human Herpes Viruses) (2)

Binding to cell surface proteoglycans (heparan-sulfate). Membrane fusion (gB and others, gH-gL). Penetration. Partially coated genome. Virus-mediated intracellular transport. Alpha TIF into nucleus. Viral DNA

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Describe features of Varicella zoster virus (VZV) - 1

Cause of chickenpox. Primary infection may be via contact or droplet infection. Virus travels via blood triggering symptoms (fever, malaise, vesicle formation on skin). Virions shed droplets and from fluid form skin lesions (vesicles).

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Describe features of Varicella zoster virus (VZV) - 2

Remain latent in sensory ganglia of spinal nerves (diagram)

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Describe features of Herpes Simplex Virus (HSV) - 1

HSV-1 mostly oral herpes on face and mouth, causes 30% of neonatal herpes. HSV-2 mostly genital herpes, causes 70% of neonatal herpes. Transmitted by direct contact

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Describe features of Herpes Simplex Virus (HSV) - 2

Latency in ganglia of trigeminal cranial nerve (oral herpes), or sacral ganglia (genital herpes)

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Describe features of Herpes Simplex Virus (HSV) - 3

Reactivation of oral herpes may cause virions to take different routes to that of primary infection (via different nerves). Immunosuppressed patients may develop encephalitis or meningitis

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Describe features of Epstein-Barr Virus (EBV) - 1

Causes infectious mononucleosis (glandular fever). Infects via complement receptors of some epithelial cells & B lymphocytes and remains latent in B lymphocytes – transmitted via saliva

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Describe features of Epstein-Barr Virus (EBV) - 2

Lymphocytes are transformed by presence of virus & stimulated to proliferate. Genetic predisposition linked to resistance to Malaria may be the cause of (Burkitt’s) lymphoma associated with EBV infection in Africa

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Describe features of Human Immunodeficiency Virus (HIV)

-

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Describe features of Epstein-Barr Virus (EBV) - 2

Lymphocytes are transformed by presence of virus & stimulated to proliferate. Genetic predisposition linked to resistance to Malaria may be the cause of (Burkitt’s) lymphoma associated with EBV infection in Africa

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Describe features of Human Immunodeficiency Virus (HIV)

Free virus, binding to host T cell via CD4 receptor, penetration/uncoating, reverse transcription (reverse transcriptase), integration into T cell DNA (integrase), replication transcription/translation, assembly, budding, release immature virus

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What is the therapeutic strategy for HIV? (1)

Administration of combination of drugs (HAART) which inhibit specific viral enzymes. Nucleoside analogues, reverse transcriptase inhibitors (azidothymidine, AZT). Non-nucleoside reverse transcriptase inhibitors (nevirapine)

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What is the therapeutic strategy for HIV? (2)

Viral protease inhibitors (saquinavir)

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Describe features of post-exposure prophylaxis (PEP) - 1

28 day course of anti-retrovirals used to prevent infection in case of accidental exposure to HIV (e.g. healthcare workers). PEP should be offered and initiated within 72 hours of exposure

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Describe features of post-exposure prophylaxis (PEP) - 2

PEP can reduce risk of HIV infection by over 80%, provided full 28 days course of ARVs is adhered to. Only 57% of people who initiated PEP have completed full course and rates were at 40% for victims of sexual assault

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Describe features of anti-viral chemotherapy (1)

Antibiotics (inhibit metabolic processes specific to prokaryotes e.g. cell wall synthesis, 70S ribosome protein synthesis) have no effect on viruses. Antiviral drugs need to be specific to viral enzymes and life cycle processes

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Describe features of anti-viral chemotherapy (2)

Amantadine (blocks uncoating of influenza virus). Acyclovir (deoxy-guanosine triphosphate analogue dGTP, inhibits herpes DNA polymerase). Cidofovir (deoxy cytidine-triphosphate dCTP) analogue, broad-spectrum inhibitor of viral DNA polymerase

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Viruses

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