Virology Flashcards
What is the attachment receptor for most Rhinoviruses?
ICAM-1
Where do DNA viruses replicate generally?
The nucleus except Poxviruses that rep in the cytoplasm
Which viral proteins are synthesized first?
Non-structural - eg DNA and RNA polymerases
What is the difference between +sense and -sense RNA genome viruses in terms of their amplication?
What does Protein kinase R do?
Inhibits protein translation
What is an example of a virus that fuses in order to penetrate?
HIV
What are some viral strategies for blocking CD8 T cell recognition of infected cells?
Endocytose MHC I
Alter MHC I peptide
Block TAP on both sides
Bind to and retain MHC I in the ER
Inhibit the proteosome
Decrease MHC I gene transcription
What are the 4 mechanism of systemic spread in the body?
Local epithelial spread
Haematogenous
Via lymphatics
Neural
What is autocleavage?
The process by which long peptides cleave themselves into smaller active proteins
What are koplik spots?
Areas in the mouth where measles virus initially replicates, they are red due to lymphocytes
True or false, LN enlargement is due to direct viral action
False, it is due to immunopathology
What is an example of a disease where CD8 T cell cause pathology?
CD8 T cell kill liver cells and recruit neutrophils and monocytes in Hep B infection
What are some strategies viruses use to evade interferon immune response?
Interference with the PKR (protein kinase R) pathway
- dsRNA-binding protein
- PKR binding protein (vaccinia)
- Abundant small RNAs (adenovirus)
What type of viruses carry their own polymerase?
-sense RNA viruses
retroviruses
What is the function of M cells?
Ingest and deliever Ag to APCs beneath them
What is an example of virally induced autoimmunity?
Myelin basic proteins are cross reactive with influenza proteins = demyelination and transient paralysis
or
Polyclonal B cell activation by EBV
What type of cell layer do most viruses enter through?
Serous epithelium
What does type II interferon do?
Activate macrophages
Inhibit viral replication
Enhances MHC I and II expression
What are two strategies enveloped viruses use to get out of the cell?
Budding
Release via the vesicle secretory pathway
What are common viral causes of URTI?
Adenoviruses
Rhinovirus
Coronavirus
What receptors does measles virus use?
CD150 and CD46
What cell types produce type I interferon?
virally infected:
DCs
Tissue cells
dsRNA
Macrophages
What is an example of a virus that will kill a developing foetus?
Smallpox
Which inteferons are considered type II interferon?
Interferon gamma
What is the ecilpse period?
The period between a virus infecting cells and mature virions assembling in the infected cells
T/F measles virus is breathed out not coughed out
True
What don’t viruses that infect the alimentary tract have?
Envelopes
What are some examples of viruses that enter via the resp tract and cause disease locally?
Rhinovirus
Influenza virus
RSV
What is secondary viraemia?
When virus is released after replicating in tissue after an initial infection
What are two ways viruses penetrate a cell?
Fuse with membrane or are endocytosed
How are non-enveloped viruses released from the cell?
They accumulate in the cytoplasm or nucleus into the cell lyses
What types of viruses does the PKR system work against?
Mainly RNA viruses as they are the main producers of dsRNA
What are some examples of viruses that enter via the resp tract but cause systemic disease?
Measles and mumps
Rubella
varicella-zoster
What are some viruses that enter via conjunctiva?
Adenovirus, HSV, enterovirus
How are viruses classified using the baltimore system?
I. dsDNA
II. ssDNA
III. dsRNA
IV. +sense RNA
V. -sense RNA
VI. +sense RNA (retroviruses)
Direct viral damage to infected tissue can include 4 things, list them.
Lysis of cell during replication (eg enterovirus)
Release of toxic viral produces
Apoptosis
Loss of cell function (eg rhinovirus and cilia stasis)
The cytokines responsible for fever are?
IL-1 and TNF
What are some strategies viruses use to interfere with cytokines immune response?
Inhibit receptor production
Inhibit interferon production
Interfere with interferon function
What are three mechanisms of genome modification
Random mutation - viruses don’t have proof reading
Reassortment - Swapping of genome segments for 2 viruses that have segmented genomes and infect the same cell
Recombination - exchange of stretches of genome for 2 viruses that infect the same cell
When endocytosed how do viruses get their material into the cytoplasm?
Low pH in the lysosome trigger conformational change in viral protein that allows fusion with endosomal membrane
Or endosome is lysed and virus is released
How does ancyclovir work?
It is incorporated into the extending chain but does have the -OH group required continue extension
What do type I interferons do?
Activate NK cells
Inhibit viral genome replication
Enhances MHCI presentation
What cell types produce type II interferon?
NK cells (and T cells)
What are the stages of viral replications
Attachment
Penetration
Uncoating
Genome replication
RNA synthesis
Protein translation
Assembling
Budding/Lysis
4 viral induced consequences?
- Lysis
- Chronic infection - slow release of virion
- Latent infection - dormant then lysis
- Tumour transformation
What is the latent period?
The period between viral penetration and appearance of virions outside the cell
Over what size with droplet load in the nose?
>10 microns
What is an example of a tumour forming virus?
Oncogenic retrovirus
What are the barriers to infection in the ailmentary tract?
Constant movement of stomach contents
Stomach acidity
Intestinal alkalinity
Lipolytic bile
Proteolytic enzymes
Mucus
Macrophages
IgA
What is an example of a chronic virus?
Hep C virus
What is the viral cause of croup?
Parainfluenza
Where does influenza cause disease in the resp tract?
Large airways mainly
rarely in the alveoli
What are inclusion bodies?
Accumulations of viral protein near the site of viral exit from a cell
What are some strategies viruses use to evade the NK cell immune response?
- Mutations in ligand for activating receptor-MCMV
- Virus-encoded MHC class I-like molecules - HCMV
- Upregulation of non-classical class I molecules- HCMV
Which viruses are people without NK cells susceptible to?
CMV and varicella
What type of drug is ancyclovir?
Nucleoside analogue
What are some viruses that use the alimentary tract to gain entry but cause disease elsewhere?
Hepatitis A
Poliovirus
What are the 2 mechanisms of viral infection leads to tissue damage?
Direct damage by virus
Immune respond mediated damage
Name 4 mechanisms to stop viral replication?
Antibody neutralisation
NK cell killing of infected cells
Interferon
Anti-viral drugs
What is an example of a latent virus?
Herpes
How is diarrhea cause by virus infection?
- Decreased fluid absorption due to destruction of entercytes
- Viral secretion of NSP4 that causes fluid to be secreted by remaining enterocytes
What is an example of a lytic virus?
Enterovirus
What is the pathogenesis of rotavirus?
It infects and kills intestinal villi and M cells causing diarrhoea. It has a triple peptide capsid for protection
What are the most common viral causes of bronchiolitis?
RSV and parainfluenza
DNA viruses don’t usually carry their own polymerase but which do?
Poxvirus because it replicates its genome in the cytoplasm and Hepadna because it is very complex
What is the consequence of glycosylation of viral proteins in the RER and golgi?
They are deposited on the host membrane
What barriers against infection are present in the respiratory tract?
Cilia,
alveolar macrophages
Temperature 33C
secreted IgA
Mucus
What are some strategies viruses use to evade the immune response?
Lie dormant in cells - eg HSV in herpes
When does Ab responses cause pathology or contribute to disease?
When Ab-virus complex mediated endocytosis of virus via FcR into cells
With Ab-Ag complexes are deposited - eg kidney failure in chronic Hep B carriers
What is an example of a virus that requires two receptors?
HIV - it requires CD4 for initial attachment and conformational change of its gp120 protein so that it can bind to CCR-5 and form a stronger connection.
How do non-enveloped viruses assemble?
- Spontaneous as the assembled state is the lowest energy
- Require proteolytic cleavage to induce the final state
What virus does ancyclovir work against?
Herpes
What is the attachment receptor for influenza?
Sialic acid
What are some strategies viruses use to evade the T cell immune response?
Antigenic variation (shift and drift)
Downregulate MHCI expression
Inhibit processing of viral peptides
T/F Only proteins can act as receptors for virus attachment
False, carbohydrates can too!
What cytopathic effect is seen with RSV infection?
Giant cells
Why does downregulating surface MHC I on virally infected cells leave them susceptible to NKs?
Surface MHC I is recognised by NKs are acts as a survival signal that overrides the killing signal it gets when it recognises viral produce on the surface of infected cells
What are some viral strategies to inhibit the PKR system?
Produce small stretches of dsRNA only large enough for one monomer therefore PKR can’t activate
Produce it’s own protein to bind to its dsRNA to protect it from PKR binding
Produce homologue on eIF2 alpha that competes with actual eIF2 for PKR phosphorylation
What are some routes of entry for viruses?
Conjunctiva
Respiratory tract
Alimentary tract
Urogenital tract
Skin
Parenteral inoculation
T/F post translational cleavage of polyproteins is usually carried out by host enzymes?
False, they are usually by virally encoded enzymes
What are some ways viruses inhibit T cell priming?
Vaccinina and HCV block cytokine production
HSV blocks signal transduction
Measles and CMV block T cell stimulation
What are the six determinants of viral trophism?
Specific receptor availability
pH
Availability of macrophages and lymphocytes
Cell polarity
Optimal temperature
Presence of activating enzymes
What are some genetic factor that alter susceptibility to virus infection?
Don’t produce a virus’ receptor eg CCR5 in HIV - good
Defect in Ig class eg IgG2 increased susceptibility to 2009 flu
MHC polymorphisms - some are good or bad
Why doesancyclovir only work in virally infected cells?
It requires modification by herpesvirus thymidine kinase
Where do RNA viruses replicate usually?
In the cytoplasm, except influenza that replicates in the nucleus
What cells do measles virus infect?
Macrophages
Lymphocytes
DCs
T/F Some virus encodes oncogenes?
True
Why doesn’t Protein Kinase R act all the time?
It must be activated
What size droplet will lodge in the alveoli?
Which interferons are considered type I?
Interferon alpha and beta
What is the clinical presentation of congenital rubella syndrome
Microcephaly
Congenital heart defects
Cataracts
What do RNA viruses need that the host cell can’t provide?
RNA dependent RNA polymerase
What is antigenic drift?
Random mutations in RNA genome that causes altered structured glycoprotein are selected for as they allow avoidance of Ab response - eg influenza and HIV
What are some non-genetic factors that increase susceptibility to viral infection?
Age
Pregnancy
Multiple infections
Malnutrition
What is an examples disease with CD4 T cell responses cause pathology
Rash in measles due to CD4 T cell recruiting eosinophils
How is Protein Kinase R activated?
It is activated when it is recognises dsRNA (only viruses produce this)
Two Pkr monomers wrap around dsRNA bringing their KD domains closer therefore allowing phosphorylation and activation
What are four outcomes of viral infection?
Death
Full recovery
Permanent damage - eg polio
Chronic infection - eg HSV
What is an example of a virus that is endocytosed to penetrate?
Togavirus
