Thiele Flashcards
What are the stages of viral replication?
- recognition
- attachment
- penetration
- uncoating
- transcription
- protein synthesis
- replication
- assembly
- lysis and/or release
Describe recognition in the process of viral replication.
- through recepto-ligand interactions
- viral associated proteins (VAP) bind to specific cellular receptors
Describe attachment in the process of viral replication.
- specific cell receptors will bind to the VAPs on the viral nucleocapsid or membrane
Describe penetration in the process of viral replication.
- viropexis - small viruses slip through the membrane (done by chanse)
- Membrane fusion - an F-protein allows fusion of viral membrane with cellular membrane
- Receptor mediated endocytosis - VAP-receptor binding leads to phagocytosis of the viral particle
Describe uncoating in the process of viral replication.
- viral RNA replicates in the cytoplasm
- viral DNA replicates in the nucleus
- viral genetic material released into the proper location without cover of the capsid or membrane
- full uncoating may be done only by viral enzymes after cellular enzymes partially uncoat the viral genome
Define monocystronic.
- each mRNA produces one specific protein
Define polycystronic.
- each mRNA produces multiple proteins in one single chain
- individual proteins can be produced by start and stop codons or by cleavage of the large protein
Define monopartite.
- all genes linked on a single piece of RNA or DNA
Define multipartite.
- viral genes are distributed in several pieces of RNA or DNA making up the whole genome
Define polarity of the RNA strands.
- Positive strands can be read like mRNA
- Negative strands can not be read like mRNA
What are the three phases of transcription and translation of DNA viruses?
- Immediate early phase - shutting down host cell materials
- Early phase - genome is replicated before the transcription of genes
- Late phase - structural, capsid and glycoproteins made
Discuss (+) RNA viruses.
- (+) RNA will act as mRNA
- first protein produced is RNA polymerase
- uses host ribosomes
- produces (-) strands for template for making more (+) strands
Discuss (-) RNA viruses.
- RNA dependent RNA polymerase accompanies genome
- polymerase then produces (+)RNA and viral capsid proteins
How does a retrovirus funciton/replicate?
- contains a RNA-dependent DNA polymerase - produces a cDNA strand from a RNA strand
- integrase then integrates then cDNA into the host cells DNA and new viral RNA/proteins are produced by host tools
What are the four processes associated with viral genetics?
- recombination - genetic exchange of viral and host DNA
- reassortment - different genes are assembled together in progeny virus
- transcapsidation - protein capsid of one strain and genome of another are put together
- marker rescue - helper virus stimulates can reactivate a virus via recombination
What are the four main time frames for a viral infection?
- Early phase - time from attachment to genome replication
- Eclipse phase - time from attachment to production of virions
- Late phase - time from genome replication to extracellular virus detection
- Latent period - time from attachment to extracellular detection of virus
What are the host and viral factors that help determine viral pathogenesis?
- interaction of virus with target tissue
- cytopathological activity of the virus
- immune response
- immunopathology
What are the three types of cytopathogenesis of viral infections?
- abortive
- lytic
- persistent infections
Discuss an abortive infection.
- the host stops the virus from replicating (due to temperature, inappropriate enzymes or lack of receptors)
- virus does not have appropriate genetic material
Discuss a lytic infection.
- morphological changes occur by destruction of the host cell or by fusion into multinucleated cells
What are the different methods of a lytic infection?
- membrane changes
- necrotic and degraditive changes in genome
- inclusion bodies
What are the different patterns of persistent infections
- chronic infections
- Latent infections
- recurrent infections
- transformation
What are three methods of immune system escape by chronic infections?
- patching - collect glycoproteins in groups
- capping - glycoproteins move to top of host cell
- shedding - removal of all glycoproteins so cell cannot be seen
How do latent infections persist?
- integrate into host genome
- play a hide and seek by rapid replication to states of no replication
What are the host cells defense against viral infections?
- natural barriers (innate immunity)
- Antigen specific immune response (neutralizing/non-neutralizing antibodies)
- Cell mediated responses
- Interferons - activates cell mediated response and halts infections
Name some determinants of viral disease.
- nature of exposure
- immune status
- age
- general health
- viral dose
- genetics of the virus and host
What are the clinical stages of viral infections?
- incubation period - virus gains access to cell and prduces virus
- prodrome - non-specific symptoms (infectious)
- disease - clinical illness
What is transmission of virus dependent upon?
- source of the virus
- tissue site of replication
- ability to endure
- enveloped or not
What is the structure of the herpesvirus family?
- linear dsDNA
- icosahedral virus particle
- enveloped
What is the replication sequence of Herpesviruses?
- fusion with host membrane releasing nucleocapsid into cell and delivery into nucleus
- Immediate early, early and late phase protein production
What are the stages of pathogenesity and immunity of the HSV 1, 2?
- initiated by direct contact
- cytopathology results in lesions
- virus avoids Ab by cell to cell spread
- virus establishes latentcy
- virus reactivates due to stress
- cell mediated immunity is required for resolution
What are the clinical syndromes of HSV 1 and 2?
- Gingivostomatitis - lesions along third trigemianal nerve
- Eczema herpeticum - infection of open wound
- Herpes keratoconjunctivitis - infection of eye
- Herpetic Whitlow - infection of the finger
- Herpes encephalitis - brain damage
- Pharyngitis
- Herpes Gladitorium - infection of body/trunk
- Genital Herpes (HSV-2)
- Neonatal Herpesvirus - frequently fatal
How is herpes 1 and 2 diagnosed?
- clinical picture (lesions in noted areas)
- Cytology (Tzanck smear, syncytia, Cowdry type A bodies)
What are the treatments for HSV-1,2?
- idoxuridine - inhibits viral DNA polymerase
- vidarabine - analogue that forms a faulty DNA strand
- Acyclovir - block guanosine uptake
Discuss the characteristics of Varicella virus?
- childhood exanthems
- pock-type lesions - cover whole body and pocks at different stages
- transmission through respiratory droplets
Discuss the characteristics of Zoster virus.
- primarily a disease of adults
- pock type lesion over a dermatomal area
What is the pathogengenesis of the Varicella virus?
- replicates in the respiratory tract
- viremia to secondary infection site
- replication in secondary organ
- viremia and virus goes to skin and rash occurs
- incubation period 10-11 days
- contagious during rash until crusted over
What is the pathogenesis of the Zoster virus?
- re-activation of the virus occurs along the dermatomal area
How is the Varicella-Zoster virus diagnosed?
- clinical picture and recognition of outbreaks
What is the treatment/prevention for Varicella-Zoster virus?
- treat the symptoms
- Acyclovir may shorten the course of disease
- Zoster immune globulin - if severe
How is the Epstein-Barr virus spread?
- saliva
- blood transfusion and bone marrow
What is the pathogenesis of EBV?
- virus infects cells in oropharynx and spreads through lymphatics to infect B cells
- virus replicates in B cells and causes Lymphoma (T cells attack B cells) then virus goes latent
What diseases are EBV associated with?
- Infectious Mononucleosis
- Burkitt’s Lymphoma
- Nasopharyngeal Carcinoma
- Hairy Oral Leukoplakia
Discuss Infections Mononucleosis
- clinical triad of: sore throat, fever (high), and lymphandenopathy/hepatosplenomegally
- Atypical T lympocytes (Downey cells) produced
- presence of a heterophile antibody is diagnostic
Discuss Burkitt’s Lymphoma.
- B cell lymphoma that is associated with EBV and malaria
- malaria is thought to drive B cell proliferation
Discuss Nasopharyngeal Carcinoma
- B cell proliferation due to Euphorbacea plant agent with infection of EBV will = tumor
Discuss Hairy Oral leukoplakia.
- infeciton of epithelial cells of the tongue = white coat
- seen in AIDS pts
What is the epidemiology of Cytomegalovirus?
- neonates and breast fed children - crosses placenta
- sexual transmission
What diseases are associated with cytomegalovirus?
- Non-classical mononucleosis
- Mental retardation
- Microcephally
- Organ transplant infection
How is cytomegalovirus diagnosed?
- cytology - owl-eye inclusion body
What is the treatment for cytomegalovirus?
- Ganciclovir - blocks quanosine uptake and stops viral DNA formation
- Foscarnet - stops phosphorylation of nucleotides
What are differences in Non-classical mononucleosis?
- less severe sore throat
- no rise in the heterophile antibody
What are the diseases associated with HHV-6?
- Exanthem subitum (Roseola)
- Kaposi’s sarcoma
- Hodgkin’s disease
- Multiple sclerosis
What are the characteristics of Roseola infantum?
- rapid onset of fever
- rash that lasts 24-48 hours
- lifelong latent infection in T-cells
What is the pathogenesis of HHV-6?
- needs HHV-7 as a helper virus
