Viral microbio Flashcards
What is the definition of a virus? How do viruses get their name?
A virus is an OBLIGATE intracellular PARASITE, with a genome comprised of DNA or RNA
Within the appropriate cel, the viral genome is replicated and direct synthesis of new viruses, and then transported
Viruses are SMALL- 1uM to 10nm
Can have many shapes-bacteriophage (not human), rod, blob or round
No standard way of naming-can be after disease, the person that discovered it, place it was discovered, part of the body it affects, way it spreads, and more
What causes virus morphology?
The capsid is the main effector of morphology-Symetrical capsids, non eveloped usually make a neat round virus (eg adenovirus, picornavirus), while some viruses are envelopped (lipid derived from host membrane)-can be pleiomorhphic (measles) or rod like (ebola)
Can be both-capsid and lipid enveloppe (herpes)
What is the baltimore classification system for viruses? What are the consenses of different genomes?
A class system bases on how the virus encodes its genome and expresses it. Always has to follow DNA->RNA->protein DNA can be ssDNA or dsDNA , but has to be ds before mRNA (class 1,2,3) eg herpes, adenovirus Some code in RNA then switch to DNA then to mRNA (can have dsDNA or +RNA) eg retrovirus (class6) Some have RNA, usually direct to protein/replicate-can be +RNA, dsRNA or -RNA (has to make +RNA) (class4,5), eg: SARS, rotavirus, Ebola Viruses cannot have machinery in them-some RNA viruses use own RNA pol (RNA virus and retro)-no proofreading RNA viral genome is limited in size-use tricks (splicing and stuff) to fit as much as possible DNA viruses are larger-have space for accessory genes to avoid immune system Segmented genomes can allow better packing or recombination when packaged-leading to fast evolution)
Explain a generic virus replication cycle, the HIV replication cycle, the influenza replication cycle and the E.Bola cycle
The first step is always to enter the cell-then the genome has to become mRNA and start producing early regulatory proteins, which will help replicate the original genome-which is then transcribed to late structural proteins-make capsid and package genome, then exit (lysing the cell)
HIV uses it capsid to fuse with the cell wall (with CD4 binding), and releave RNA and proteins in cell-reverse transcriptase make DNA, then integrase adds it to host genome. The cell then automatically replicates and expresses it as its own-new RNA is used as genomic RNA and gets packaged by expressed prots-then takes membrane + proteins and exits
Influenza gets uptaken by endosomes, then escapes and RNA goes to host nucleus-highjacks host machinery to replicate RNA, then to cytosol to be expressed-and packaged after with host membrane
E.Bola is uptaken in endosomes and fuses with the membrane-releasing it. then -RNA is copied and made into mRNA-the -RNA gets packaged by proteins made by mRNA, and most of the rest inhibit host response. Capsid formation and takes lipid from host cell
What are laboratory signs that you have viruses in your culture? what techniques are uses to investigate viruses?
In a culture, the cytopathic effect is due to visible lysis of cell in a culture, usually a result of virus infection. Viruses also cause formation of plaques-of dead cells-indicating where it has spread-and using a dillution assay (how many plaques at low concs) can get an idea of how much virus is present
Can also get Syncytia-which is as virus infect cells, they fuse into some sort of mega cell-visible on culture
Other classic methods are FISH-or anti-virus protein AB to see which cells are infected/where in the cell protein is
Genome can be detected with PCR, AG with ELISA, particules with EM/HA, Cytopathic effect by cultures, and finally can measure AB against virus (serology)
Explain the strategy of diagnosing a virus.
Idea is to indentify the source and what specimen it is-have to determine what the purpose of the test is (surveillance or therapy), who it will be used by (lab/field, etc), what stage of disease you want to catch (AB response or active replication)
Explain changes viruses can undertake in a lab, its use, and what it revealed about noroviruses
Mention how we can manipulate viruses
When viruses are cultured in a lab in cells (permissive cell lines), the virus adapt to the cells-will infect their new host better, but in turn leads to loss of fitness in actual human. This was the method used to create vaccines-attenuated ones
But norovirus or HepC dont have permissive cells-revealed that norovirus dont just infect epithelium cells, but that they ride enterococcus bacteria in the stomach to pass it and reach B cells-hard to culture
Viruses genomes are small and can be synthesis denovo, which allows creating of viruses with engineered mutations-attenuated directly, or used in therapy
List the main portals of entry for viruses, and define Iatrogenic, nosocomial, Vertical, Horizontal and germ line transmission
Respiratort, Foecal oral, Contact (lesion, saliva), animals (zoonoses-usualy bites), Blood, sexual contact, Maternal neonatal, Germline
Iatrogenic-indvantedly given by dr (contaminated needle)
Nosocomial-Aquired in hospital
Vertical-from parent to offspring
horizontal-all other forms
Germ line-part of the genome
What are the general consequences of virus entry? Describe symptoms and spread of varicella Zoster Virus, and its
Infection leads to local infection and continued dissemination (can be apical or basal release)-after disseminate, primary viraemia (virus in blood), which leads it to spread, amplify, find target organ (usually viruses prefer 1 organ) and start again (secondary vireamia =>can become systemic or go from one organ to the next
A main sign of systemic viral infection are rashes-leaves blood and enters skin, cell destroyed during replication. eg: measles give Koplik spots, measles and chicken pox can cause lesions on respiratory tract and release virus before visible rash
VZV enters through URT (primary vireamia), amplifies in organs (liver, etc) then release again (secondary), whcih infects PNS cells and cause the rashes-begnign in children. if immunity is impaired, latent VZV can be released later as shingles-spread back up the neuron and becomes much more painful
What is viral tropism? Recall mechanisms of HIV tropism, Measles tropism and Influenza tropism
Viral tropism is the predilection for viruses to infect certain tissues and not other-can be determined by interaction (receptors-susceptability), or to use the cells (permisivity) or wether the virus can reach (accessibility)
HIV tropism is in CD4 cells-and is determined by its interactions with CD4 and CCR5 (on macro) or CXCR4 (on T cells)-binds the receptors and uses it to internalise, Usually starts with macrophages, then switches tropism to T cells
Measles also uses receptors-CD155 and SLAM, and to internalise into immune cells in airway- use it to go around (like a carrier)(immune supression). In late MV infection, use bind Nectin4 to exit blood stream back into epithelia, infect and spread
Influenza-has NA and HA on its surface-enters in endosome and low pH causes HA cleavage-triggers fusion with barrier and release. Importantly, Influenza tropism is dependent on host Trypase clara which cleaves HA-usually produced by clara cells in epithelium (lungs and stuff)-but can only infect cells that have seceted protease around-mutations of HA allows much more systemic (increased tropism) viruses
Describe patterns of virus infections
Acute infection usually start at entry-and rise fast as virus passes innate defences (then estabilshement), and cause infuction of adaptive response. Once that is in full swing, virus levels go down, untils levels are under the innate activation threshold-cleared (and some cells are put to memory) eg: Rhinovirus, Rotavirus, Influenza
Acute infections are not always cleared (smallpox, dengue (leakage of blood from capilatires)
Persistent or smoldering viruses-levels rise after infection and never drop back down-usually causing death
Persistent, Latent-initial acute infection, but when cleared-hides away and waits. When immune is a bit more down, virus reemerges and causes another acute response
Persistent, slow-initial acute infection, but never completely cleared-replicate slower, and after an event (time, immunosupress) reemerged and kills host
Give details on viral acute infection and accidental pathogenesis, persistent viral infection, latency and oncogenesis
Acute viral infection can damage tissues that arent intendeded as targets-polio causing paralysis (poliomyelitis), or Rubella in foetus causing deafness
Persistent viral infection can have many forms
Low levels of replication and spread (like wart (papillomavirus)
Chronic carriers-Hep C and B
virus is carried but not present until immunity wanes-Herpes, etc (latency)
Strategy for viral persistance are usually MHC I downregulation, and compensate (ctyomegalovirus produced MHCI like HCMV), or some escape CTL by mutation (HepC)
Can also target tissues with reduced immuno surveilance (CNS, Skin)
Latency is when the virus exists but doesnt replicate or produce any proteins-except those pushing latency. Herpes in neurons-neurons dont divide and can contain hundred of copies. 1 acute infection (eg skin) and moves down into neuron. 2) infection stays latent, doest activate 3) reccurent infection-spread back up the axon, and reinfects epithelial cells (can also spread to CNS-BAD)
Oncogensis-viruses can cause cancer (encode oncogenes) and interfere with cells cycle-papilloma virus forces cell into S phase, HTLV1 can cause adult leukemia. HBV causes heptatocellular carnicoma-and spreads much more than HIV-vaccine tho
HCV can also cause cancer-no vaccine
Epstein barr-Most common infection in world (95% of people have it)-usually causes mononucleusos in teenargers, and stays latent. But can cause Burkitts or Hodgkins lymphomas, and others
Explain factors that can impact the outcome of viral infections, especially viral sequence, viral load, co infection, genetic resistance and predispositions
Viral sequence-different stains of the same viruses can have different effectiveness-a single mutation can change between attenuated and live virus
Viral load-the amount of virus initially taken in-for smallpox, 1st child to have it will develop it normally, but if 2nd gets it from them-higher load and therefore worse outcome
Co-infection-secondary infection due to immunosupression, secondary bacterial infections (morns of taubengerger), or viral (eg: HHV8 causes sarcoma in HIV patients, or Hep delta virus-infects only HBV patients and stops it, but cause liver damage)
Genetic resistance-CCR5 mutations makes immune to HIV, KIRs can change HCV
Predisposing conditions-asmthatics and respiratory virues, immuno suppresion, obesity and diabetes, pregnancy
Define prophylaxis and Therapy approach to treatment. Mention the main exemple of each
Prophylaxis-preventing disease before causing agent is acquired eg: vaccination (live or innactive, herd immunity-safety>efficacy-governement level)
Therapy is treating the disease after the infection eg: Antiviral drugs (rational design-specific target group-individual level)
What is the immunological basis behind vaccination? List the different forms of viral vaccines. What are most human vaccines?
Vaccination is made to induce an inital adaptive response to a safe version of the virus-which will lead to memory T and B cells to be produced and kept-when infected again, reaction will be faster, more adapted, stronger (faster into adaptive immunity, more AB and stuff)
Viral vaccines can be natural: attenuated, Inactivated, Fractionated or cloned: Live vector virus, DNA vaccine or subunit/virus like vaccine
Most human vaccines are live attenuated- few inactivated, influenza (subunit), and few cloned)-growing tho
