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121 Cards in this Set
- Front
- Back
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What are the basic requirements of a viral initating infection and why are they important?
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-enough cells must be present otherwise the immune response will kill all
- cells at infected site must be accessible, susceptible and permission (virus wont be able to replicate) -local host defenses must be absent or ineffective |
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Describe the four major types of virulence genes
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1. Affect viral replication
2. modify host defenses 3. facilitate spread within the host and between hosts 4. specific toxins |
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How are the virulence genes measured in culture?
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they cannot be measured in culture/ they have no effect on viral growth in culture
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Describe the 2 essential features of global eradication
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Virus must have only 1 host (polio) and the infection or vaccine must provide lifetime immunity (polio)
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What tkype of antigenic variation does HIV demonstrate?
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antigenic drift within the host due to it high rate of replication
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What is a prodrug?
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a non toxic drug that is change in 1 step to an antiviral form in the presence of viral kinase (only present with an infection)
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What is a proprodrug?
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Needs to be modified, before becoming a prodrug.
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What is an example of a prodrug?
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acyclovir reuires phosphorylation by both a viral kinase and 2 cellular kinases before incorp into growing DNA strand by viral DNA pol. This stops replication because it lacks 3' OH needed to add another nucleotide
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What is an example of a proprodrug?
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Valtrex. Needs to have valine removed before it becomes acyclovir. It is taken up by host cells better than acyclovir
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What are 6 ways that a virus can be shed or transmitted?
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Respiratory secretions, saliva, feces, blood, urine(semen/milk), skin lesions
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How are viruses spread through respiratory secretions?
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Aerosolized droplets during sneezing (requires close contact for infection)
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How are viruses spred through saliva?
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aerosolized transmission, kissing, contaminated fingers, pet-licking
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what are limitations of viruses spred through feces?
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Must be able to tolerate harsh environments (hepB is inactivated by bile)
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What are viruses spred through urine, semen or milk?
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URINE: Hantavrus
SEMEN: HIV, herpes, HPV, hepB MILK: CMV and mumps |
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What is virurea?
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Viral particles in urine (replicated in kidney)
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How are viruses spread through skin lesions?
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usually requires direct body contact
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What viruses are spread through skin lesions?
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Pox, Ebola, herpes, papilloma
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Define virulence
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the capacity of infection to cause disease
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Define virulent
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virus causes severe disease
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Define avirulent
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virus causes no disease
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Define attenuated
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virus causes mild disease
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How are attenuated viruses useful?
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excellent tools for studying how viruses function, vaccines
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How is virulence measured?
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LD50, PD50, ID50, mean time to death, tissue damage assessment
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What is LD50?
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The concentration of the virus necessary to kill 50% of the infected animals
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What is PD50?
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The concentration of the virus necessary to cause paralysis of 50% of the infected animals
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What is ID50?
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THe concentration of the virus necessary to infect 50% of the animals exposed
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What are four major types of virulence genes?
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1. Affect viral replication
2. modify host defenses 3. facilitate spread within the host and between hosts 4. specific toxins |
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How is the viral replicaiton ability altered?
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Genes that affect replication in mutants by reducing replication in animal hosts/cultrtures, or altering noncoding regions that affect replication (polio - 5'UTR reduces replication in nuronal cells/brain cells)
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How do viral proteins modify host defenses?
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mutations in genes that affect virulence in host, or inducing apoptosis
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Define virokine
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virus produced, mimics cytokins or growth factors
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Define viroceptors
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homologues of host receptors
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How do viruses induce apoptosis?
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indirectly - induces apoptosis in uninfected lymphocytes release of factors from infected macrophages (African Swine Virus)
directly - replication of virus in cell induce death (hepatitis) |
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How does rotavirus cause gastroenteritis?
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by release of nsP4 protein
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What HIV proteins are toxic to cultured cells and what effect do they have on cell?
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TM affects membrane permeability
SU affects influx of calcium |
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What do both variola and vaccinia produce that affects host immune system?
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They both produce a complement inhibiting protein. (11 amino acid sequence difference - Variola is 100x more effective)
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What was gist of Australia's rodent problem & killer virus "scandal"
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tried to prevent mouse replication by engineering virus that caused antibody against egg cell - didn't work, so they added gene for IL4, to increase antibody production. Result: killed all mice treated with virus, and 50% of mice previously vaccinated. published - possible recipe for terrorism
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Define epidemiology
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the study of occurrence of disease in a populaiton
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What factors are assessed in an epidemiology study?
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mechanisms of transmission, risk factors for infection, size of population needed for transmission, geography(season), methods of control
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What is necessary for viral transmission to be successful?
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virus must spread form one host to another,
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Define reservoir host
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the species that is common host, but may be transmitted to other species
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Define zoonosis
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viruses tht infect humans and animals/insects
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What are the physical characterstics that affect transmission of enveloped viruses?
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They are delicate, susceptible to low pH, transmitted via aerosols, secretions, injections, organ transplants
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What are the physical characterstics that affect transmission of naked viruses?
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Hardier, tolerate drying, detergents, low pH, heat. Transmitted via respiratory, fecal-oral or via fomites
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Define fomites
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contaminated objects
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Define Iatrogenic transmission
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healthcare worker caused (unsterilized toods, infected worker)
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Define Nosocomial transmission
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acquired in hospital
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Why would some viruses only be found in certain geographical regions?
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There may be a reservoir host that only lives in that area
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What are some observations with seasonal occurances of certain viruses?
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No clear why, but respiratory in winter and enteric in summer, related to humidity? arthropod vectors?
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Describe viral spread to skin
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many viruses produe rashes during systemic infection, main cause of lesions is destruction of cells by virus, mouth and throat can also show lesions. Mouth ulcers are diagnostic for measles
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Describe viral spread to organs (ie liver, spleen, bone marrow & adrenal glands)
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All these organs have sinusoids lined w/macrophages, viruses can pass thru macrophages theninfect deeper organ tissues, others are transcytosed and emerge to infect to tissue
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Describe viral spread to organs (ie CNS, connective tissues, skeletal & cardiac muscles)
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These tissues have basement membrane between tissues and blood. part of the blood/brain barrier.
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Describe viral spread to organs (ie renal glomerulus, pancreas, ileum and colon)
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These organs lack sinusoids but have fenestrations in endothelial layr. Virus must adhere to cell by specific receptors (high concentrations needed) can invade deeper tissues through pores.virus can be carried by infected monocytes
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Describe viral spread to the fetus
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Some viral infections can lead to infection of fetus (rubella, HIV, CMV). The barrier between mother and fetus is leaky. Delivery and breast feeding are additional possible routes of infant infection.
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What congenital infections cause fetal death & infection?
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Small pox virus, parvovirus, various alpha-herpes viruses
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What congenital infections cause congenital defects?
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CMV, rubella virus
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What congenital infections cause immunodeficiency?
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HIV type 1
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What congenital infections result in inapparent infections resulting in lifelong carriers?
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Murine leukemia virus (mouse) Avian leukosis virus (chicken)
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How does herpes affect the newborn?
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Congenital: ~60% mortality rate
Ocular: common CNS: brain damage, blindness, deafness, seizures etc |
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Define tropism
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affecting (infecting) only certain tissues
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Define pantropic
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infect and replicate in many cells and tissues (herpes, yellow fever)
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Define enterotropic
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replicates only in the GI system
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Define neurotropic
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replicates only in vervous system cells
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What does tropism determine for the virus
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to some extent the pattern of infection, pathogenesis and survival of virus
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What are some factors that determine tropism?
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-cell receptors for virus (correct form and accessible)
-cell proteins that regulate viral transcription (hep b has a liver specific enhancer) -cellular proteases (some v require host cell proteases to become infectious - influenza HA cleaved by tryptase Clara, limiting infection to respiratory) |
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Define shedding
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infectious virion release from infected host
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Difference between localized and disseminated infections?
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localized shed locally at primary site of replication, while disseminated infections can be shed from many different locations
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Define pathogenesis
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production and development of disease
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define disease
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change in the state of health
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what are the determinants of viral pathogenesis?
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interactionof virus w/target tissue, ability of infection to kill cells, immunophology
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what determines interaction of virus w/target tissue?
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access to tissue
stability of virus in host capacity to establish viremia |
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what dtermines ability of infection to kill cells?
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efficiency of replication
inhibition of macromolecules synthessis |
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What determines immunopathologyof virus
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interferons, t cell responses, antibody: complement, antibody-dependent cytotoxicity
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What are the determinants of viral disease
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nature of the disease (target tissue & strain of virus)
severity of the disease (ability to cause cpe, immune response, quantity, genotype) |
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What are the basic requirement for initiating infection?
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enough viruses to iniate
cells at infections site must be accessible, sussceptible and permissive local host defenses must be absent or ineffective |
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What are some areas of the body that the virus may enter?
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mucosal lining, surface of eye, skin
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What is the most common virus entry site and from what source?
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respiratory tract
infected animal cough, saliva contact |
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What are host defenses against respiratory entry?
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mucus, antibodies, macrophages
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What are three major entry sites involving mucosal lining?
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respiratory, urogenital and alimentary
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How does urogenital tract become infected?
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sexual activity results in small tears/cuts.
Some viruses infect epithelium (HPV) other deeper tissues (herpes, HIV) |
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How does alimentary tract become infected?
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if virus can tolerate or exploit harsh environment, the epithelial cells are used.. (reovirus are matured by hotst protease in GI tract)
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How is surface of eye an entry site for viruses?
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conjunctiva or cornea are susceptible, often injury related exposure. (herpes)
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How is skin used as an entry site for viruses?
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breaks, punctures (papilloma, pox) insect borne (reovirus, flavivirus) deep infections due to needles, wounds (rabies)
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How does picornavirus enter?
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polio through fecal-oral route (capsid is resistant to acid)
rhino through respiratory (irreversible disassembly in acidic conditions) |
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Describe hemotogenous spread
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virus enter bood stream, releases through epithelium or insect bites, migrate to other parts of the body and infect new cells, resulting in viremia
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What is viremia
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virus particles in blood
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what is active viremia
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due to replication of virus
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what is passive viremia
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inoculation
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What is primary viremia
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virus released after initial replication at site of infeciton (usually low concentrations)
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What is secondary viremia
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release of virions to blood after replication in other tissues due to exposure from primary viremia (higher concentrations of virion)
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What is potential problems resulting from viremia?
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spread to individuals from donated blood or from products of pooled donated blood products. (HIV)
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What is neural spread?
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someviruses enter local neurons at site of entry. Some rely on this pathway as integral part of pthogensis (rabies), others sometimes utilize (polio). Some replicate in brain but spead by hematogenous route (mumps, measles, HIV)
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Define neurotropic
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virus infects neural cells
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Define neuroinvasisve
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virus enters CNS after infection elsewhere
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Define neurovirulent
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virus can cause nervous sytem disease
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What are three types of junctions that a virus may face
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Basement membranes (CNS,skin, lungs, muscle)
Pores in membrane (kidney, pancreas, endocrine glands) Sinusoids (macrophages at junction, liver spleen, bone marrow, adrenal glands) |
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Define incubation period
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the time between inoculation and onset of disease symptoms
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Difference between long or short incubation times
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short: infection site is primary site for symptoms
long: host repsonse or tissue damage is not due to primary infection |
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Describe acute infection
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rapid production of virions, infectious virus shed for short period, rapid onset of symptoms and rapid clearing of infeciton
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Describe persistent infection
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infection not cleared efficently, virus particles continue to be produce intermittently or continuous for years, may continue for life of host, may or may not have symptoms before death
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describe latent reactivating infections
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initial acute infection w/periodic recurrences with or without symptoms but with infectious shedding
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Describe slow virus infections
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acute infection, years of continuous or periodic shedding, then symptoms preceding death
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Describe inapparent acute infection
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different from unsuccessful, produce no disease, but virions are produced, detected by presence of antibody in blood of healthy individual. (enough virus to infect but most show no symptoms i.e. chicken pox - polio)
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Describe multiple infections of chicken pox resulting in shingles
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infection via eyes or URT, replication in lymph nodes (primary viremia), infection/replication in liver, spleen (secondary viremia), infection of skin w/rash, skin infection results in PNS infection. Later: reactivation results in a new acute infection.
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What two processes lead to antigenic drift?
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1. antigenic drift (light changes of viral surface proteins after growth & selection in natural host)
2. antigenic shift (major changes in surface proteins due to genetic changes |
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when can antigenic shift occur?
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after coinfection of two strains of virus in one cell - it can recombine or reassort
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What is structural plasticity?
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the ability of the virion to tolerate mutation and retain infectivity (essential for influenza, rhinovirus, HIV) Antibody resistant mutants are common in these viruses
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Difference in serotypes between rhinovirus and polio?
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rhinovirus maintains >100 serotypes in human population while poliovirus has 3 total. So people can get reinfected with same rhinovirus but w/different capsid
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What are persistant infections
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not cleared efficientl, virus particles continue to be produced for long periods of time - virions produced continuously or intermittently. chronic if infectionwill eventually be cleared, latent or slow if continue for life of host
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How does infection become persistant?
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Ineffecive immune response
or infectionof cells with reduced immune surveillance |
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How did smallpox become eradicated?
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Large scale vaccination program. Each outbreak reported to WHO and mandatory innoculation of everyone in contact w/sick person and their contacts
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What are the features of an eradicable virus?
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Viral disease:Humans are only reservoir, long incubation period and only infectious after incubation. No persistent infections, low communicability. Easily diagnosed.
Immunology: infection leads to long-term immunity. One stable serotype, vaccine is effective. Social/political: sever disease, high morbidity/mortality. few culutral barriers to case-tracing and control, eradication form developed countries show it can be done in developing countries |
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What are two essential features for successful global eradication
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1. The virus must have only one host (no survival of virions in the environment or in other animals)
2. The infection must provide for lifetime immunity |
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What are the challenges with poliomyelities eradication?
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1. WHO used oral SABIN (mutates to virulent frequently- potential pathogenic virions releaseinto aquifers - immunocompromised may shed virus w/o sign of illness
2. DR and Haiti had 2 cases of incompletely/unvaccinated children, recombinant virues 5'UTR transformed 3. Polio stocks in many labs must be destroyed to avoid accidental release into water systems |
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What livestock disease is trying to be eradicated?
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Foot-and-Mouth Disease
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Why haven't we eradicated more viruses?
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very few meet requirements, still not well understood immunologically
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What are three types of vaccines?
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Attenuated, Inactivated and subunit
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Problems with live attenuated vaccines?
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may not induce same type of immune resonse as wild type
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Problems with killed or subunit vaccines?
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produce not new viral proteins to stimulate immune system, induce Ab response but not CTL (cytotoxic T lymphocyte) response, may not have long term memory rsponse
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Define active immunity
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adaptive immunity that is induced by natural exposure to a pathogen or by vaccination
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Define passive immunity
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antibodies produced in one individual placed in another
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problems with passive immunity
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not generally long term
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