Viral Properties and Disease? Flashcards
How to identify a virus?
Viruses can be small but have devastating consequences.
MO must be found in large numbers in all diseased animals, not healthy
Must be isolated from diseased animal and grown externally in a pure culture
It must produce same disease in animal when injected
Must be recovered from experimental hosts, isolated and compared to first host and found identical
What is a virus?
infectious obligate intracellular parasite (can’t live without host cell)
Virus has a genome (RNA/DNA)
In host cell, genome is replicated and directs synthesis of more viral components and genomes
Components affect transport of viral genome copies to new host cells
Viruses are small - seen with electron microscope 20-100nm across. Bigger than ribosome but smaller than bacteria.
Viruses have different shapes and sizes - symmetrical (adenovirus, picornavirus), enveloped - lipid envelope from host membrane - ebola virus
Virus replication cycle?
Virus finds cell and attaches to cell surface. Proteins on coat bind to receptors on host cell surface.
Inside the cell the virus uncoats, that it’s genome and components can have access to cell machinery. They don’t have their own ribosomes or translation machinery.
Virus needs to make genome copies and viral proteins, these will assemble and bud out from the cell to be released and infect new cells.
Baltimore Classification system?
- Dsgenome : adeno, herpes, papilloma, polyoma
- ssDNA; parvo
- dsRNA: picobirna, reo
- sense ssRNA; astro,corona, flavi, hepe, toga
- -ve sense ssRNA: borna, filo, orthomyxo, paramyxo
- ssRNA using dsDNA intermediate: retro
- ss/dsDNA using ssRNA intermediate: hepadna
Disease a virus causing has little to do with method of replication.
Differences between RNA viruses and DNA viruses?
RNA viruses and retroviruses use own polymerases to replicate (no proofreading) → high mutation rate. RNA viral genomes have limited size due to instability of RNA (largest = coronaviruses 30kB)
DNA viruses have larger genomes 100kB, accessory genes can modify host immune response.
Segmented genomes enable easy recombination but are more difficult to pack into cell. E,g, influenza / rotavirus.
HIV virus replication pattern?
HIV: binds to CD4+ receptors on the cell surface and co receptor CCR5, then fusing its membrane with host to deliver contents to cell.
HIV = retrovirus, then transcribe DNA from the RNA - enter nucleus and integrate with host chromosome, then make new copies.
Ebola virus replication pattern?
Ebola virus taken into cell via macropinocytosis and inside cell endosome releases genetic material, which makes copies which are then coated with the host membrane and studded with viral protein particles.
Different routes by which viruses cause infection?
Respiratory, fecal-oral, contact: lesions + saliva, zoonoses: insect + animals, blood, sexual contact, maternal-neonatal, germ line.
Iatragenic: : contaminated needles nosocomial : acquired in hospital Vertical: parent to offspring Horizontal: all other forms Germ line: part of host genome Entry to the body: skin, mucosal surfaces - respiratory, enteric, genital tract), blood bites. Dissemination - spread of the virus
Methods of viral infection?
Local infection (rhinovirus doesnt, it stays in the nose) apical release. Dissemination into blood = basal release.
Primary viraemia: spreads in the blood
Amplification in second site - organ
Secondary viraemia: another migration in the blood to secondary - varicella zoster virus (chicken pox) - enters via respiratory, can infect skin → sensory neurons (latent), reactivated when adult has herpes zoster or shingles, can cause painful rash at nerve endings.
Target organ
Systemic infection - throughout whole body - usually seen as a rash, where virus leaves the blood and enters skin to move to new host, Koplik spots in mouth form measles.
What is tropism?
The particular place a virus replicates in, it can be defined by receptor interactions - susceptibility and ability to use host cells to complete replication (permissivity) and whether the virus can reach a tissue (accessibility)
HIV Tropism?
determined by receptor use CD4 + CCR5/CXCR4 chemokine coreceptors. Mutations in CCR5 gives resistance to HIV in exposed uninfected persons.
CCR5 coreceptor on macrophages and CXCR4 predominantly on T cells.
Measles Tropism?
uses 2 receptors CD155 or (SLAM), and Nectin 4.
Influenza virus tropism?
envelope virus with spike proteins, uses them to bind to cell surface. It binds to sialic acid receptors, present on glycoproteins on cell membrane of all cells, enters through endosomes and uncoats in cell, cleavage of Haemoglutinnin protein in IV, the protease is only expressed in certain (respiratory tissues) tissues.
Pathogenicity?
ability of virus to cause disease e.g. H5 bird flu is more pathogenic than human flu
Virulence?
describes capacity of virus to cause disease, how much replication a virus undergoes, but is affected by other factors (host response).
Viral Acute Infection?
followed by viral clearance often asymptomatic, adaptive immune response provides immunity, viruses continue to circulate in population (variation)
Viral Acute Infection with accidental tissue damage?
Acute infection with accidental tissue infected with permanent damage despite viral clearance. E.g poliovirus transmitted via fecal-oral route → localized infection of small intestine. Poliomyelitis - neurovirulent virus infects motor neurons → paralysis
Viral Persistent Infection?
latent, slow, transforming → Long incubations → Oncogenesis. Hide from immune system e.g. in the skin surface e.g. papillomavirus in warts = chronic infection with low level replication of virus in tissues which regenerate, Chronic carriers of hep B/C viruses → can cause hepatocellular carcinoma - the virus is much more infections than HIV, but antiviral therapies are available.
Which Viruses can cause cancer?
Epstein barr - can cause cancer, 95% are infected, can lead to Burkitts Lymphoma, Hodgkins Lymphoma and Nasopharyngeal carcinoma - passed on in saliva.
Influenza pre-disposing comorbidities?
Predisposing co-morbidites for severe influenza: asthmatics (and other resp viruses), obesity, immunosuppression, immunodeficiency, elderly, diabetic, pregnant.
