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121 Cards in this Set

  • Front
  • Back
What are the basic requirements of a viral initating infection and why are they important?
-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
Describe the four major types of virulence genes
1. Affect viral replication
2. modify host defenses
3. facilitate spread within the host and between hosts
4. specific toxins
How are the virulence genes measured in culture?
they cannot be measured in culture/ they have no effect on viral growth in culture
Describe the 2 essential features of global eradication
Virus must have only 1 host (polio) and the infection or vaccine must provide lifetime immunity (polio)
What tkype of antigenic variation does HIV demonstrate?
antigenic drift within the host due to it high rate of replication
What is a prodrug?
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)
What is a proprodrug?
Needs to be modified, before becoming a prodrug.
What is an example of a prodrug?
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
What is an example of a proprodrug?
Valtrex. Needs to have valine removed before it becomes acyclovir. It is taken up by host cells better than acyclovir
What are 6 ways that a virus can be shed or transmitted?
Respiratory secretions, saliva, feces, blood, urine(semen/milk), skin lesions
How are viruses spread through respiratory secretions?
Aerosolized droplets during sneezing (requires close contact for infection)
How are viruses spred through saliva?
aerosolized transmission, kissing, contaminated fingers, pet-licking
what are limitations of viruses spred through feces?
Must be able to tolerate harsh environments (hepB is inactivated by bile)
What are viruses spred through urine, semen or milk?
URINE: Hantavrus
SEMEN: HIV, herpes, HPV, hepB
MILK: CMV and mumps
What is virurea?
Viral particles in urine (replicated in kidney)
How are viruses spread through skin lesions?
usually requires direct body contact
What viruses are spread through skin lesions?
Pox, Ebola, herpes, papilloma
Define virulence
the capacity of infection to cause disease
Define virulent
virus causes severe disease
Define avirulent
virus causes no disease
Define attenuated
virus causes mild disease
How are attenuated viruses useful?
excellent tools for studying how viruses function, vaccines
How is virulence measured?
LD50, PD50, ID50, mean time to death, tissue damage assessment
What is LD50?
The concentration of the virus necessary to kill 50% of the infected animals
What is PD50?
The concentration of the virus necessary to cause paralysis of 50% of the infected animals
What is ID50?
THe concentration of the virus necessary to infect 50% of the animals exposed
What are four major types of virulence genes?
1. Affect viral replication
2. modify host defenses
3. facilitate spread within the host and between hosts
4. specific toxins
How is the viral replicaiton ability altered?
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)
How do viral proteins modify host defenses?
mutations in genes that affect virulence in host, or inducing apoptosis
Define virokine
virus produced, mimics cytokins or growth factors
Define viroceptors
homologues of host receptors
How do viruses induce apoptosis?
indirectly - induces apoptosis in uninfected lymphocytes release of factors from infected macrophages (African Swine Virus)
directly - replication of virus in cell induce death (hepatitis)
How does rotavirus cause gastroenteritis?
by release of nsP4 protein
What HIV proteins are toxic to cultured cells and what effect do they have on cell?
TM affects membrane permeability
SU affects influx of calcium
What do both variola and vaccinia produce that affects host immune system?
They both produce a complement inhibiting protein. (11 amino acid sequence difference - Variola is 100x more effective)
What was gist of Australia's rodent problem & killer virus "scandal"
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
Define epidemiology
the study of occurrence of disease in a populaiton
What factors are assessed in an epidemiology study?
mechanisms of transmission, risk factors for infection, size of population needed for transmission, geography(season), methods of control
What is necessary for viral transmission to be successful?
virus must spread form one host to another,
Define reservoir host
the species that is common host, but may be transmitted to other species
Define zoonosis
viruses tht infect humans and animals/insects
What are the physical characterstics that affect transmission of enveloped viruses?
They are delicate, susceptible to low pH, transmitted via aerosols, secretions, injections, organ transplants
What are the physical characterstics that affect transmission of naked viruses?
Hardier, tolerate drying, detergents, low pH, heat. Transmitted via respiratory, fecal-oral or via fomites
Define fomites
contaminated objects
Define Iatrogenic transmission
healthcare worker caused (unsterilized toods, infected worker)
Define Nosocomial transmission
acquired in hospital
Why would some viruses only be found in certain geographical regions?
There may be a reservoir host that only lives in that area
What are some observations with seasonal occurances of certain viruses?
No clear why, but respiratory in winter and enteric in summer, related to humidity? arthropod vectors?
Describe viral spread to skin
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
Describe viral spread to organs (ie liver, spleen, bone marrow & adrenal glands)
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
Describe viral spread to organs (ie CNS, connective tissues, skeletal & cardiac muscles)
These tissues have basement membrane between tissues and blood. part of the blood/brain barrier.
Describe viral spread to organs (ie renal glomerulus, pancreas, ileum and colon)
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
Describe viral spread to the fetus
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.
What congenital infections cause fetal death & infection?
Small pox virus, parvovirus, various alpha-herpes viruses
What congenital infections cause congenital defects?
CMV, rubella virus
What congenital infections cause immunodeficiency?
HIV type 1
What congenital infections result in inapparent infections resulting in lifelong carriers?
Murine leukemia virus (mouse) Avian leukosis virus (chicken)
How does herpes affect the newborn?
Congenital: ~60% mortality rate
Ocular: common
CNS: brain damage, blindness, deafness, seizures etc
Define tropism
affecting (infecting) only certain tissues
Define pantropic
infect and replicate in many cells and tissues (herpes, yellow fever)
Define enterotropic
replicates only in the GI system
Define neurotropic
replicates only in vervous system cells
What does tropism determine for the virus
to some extent the pattern of infection, pathogenesis and survival of virus
What are some factors that determine tropism?
-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)
Define shedding
infectious virion release from infected host
Difference between localized and disseminated infections?
localized shed locally at primary site of replication, while disseminated infections can be shed from many different locations
Define pathogenesis
production and development of disease
define disease
change in the state of health
what are the determinants of viral pathogenesis?
interactionof virus w/target tissue, ability of infection to kill cells, immunophology
what determines interaction of virus w/target tissue?
access to tissue
stability of virus in host
capacity to establish viremia
what dtermines ability of infection to kill cells?
efficiency of replication
inhibition of macromolecules synthessis
What determines immunopathologyof virus
interferons, t cell responses, antibody: complement, antibody-dependent cytotoxicity
What are the determinants of viral disease
nature of the disease (target tissue & strain of virus)
severity of the disease (ability to cause cpe, immune response, quantity, genotype)
What are the basic requirement for initiating infection?
enough viruses to iniate
cells at infections site must be accessible, sussceptible and permissive
local host defenses must be absent or ineffective
What are some areas of the body that the virus may enter?
mucosal lining, surface of eye, skin
What is the most common virus entry site and from what source?
respiratory tract
infected animal cough, saliva contact
What are host defenses against respiratory entry?
mucus, antibodies, macrophages
What are three major entry sites involving mucosal lining?
respiratory, urogenital and alimentary
How does urogenital tract become infected?
sexual activity results in small tears/cuts.
Some viruses infect epithelium (HPV) other deeper tissues (herpes, HIV)
How does alimentary tract become infected?
if virus can tolerate or exploit harsh environment, the epithelial cells are used.. (reovirus are matured by hotst protease in GI tract)
How is surface of eye an entry site for viruses?
conjunctiva or cornea are susceptible, often injury related exposure. (herpes)
How is skin used as an entry site for viruses?
breaks, punctures (papilloma, pox) insect borne (reovirus, flavivirus) deep infections due to needles, wounds (rabies)
How does picornavirus enter?
polio through fecal-oral route (capsid is resistant to acid)
rhino through respiratory (irreversible disassembly in acidic conditions)
Describe hemotogenous spread
virus enter bood stream, releases through epithelium or insect bites, migrate to other parts of the body and infect new cells, resulting in viremia
What is viremia
virus particles in blood
what is active viremia
due to replication of virus
what is passive viremia
What is primary viremia
virus released after initial replication at site of infeciton (usually low concentrations)
What is secondary viremia
release of virions to blood after replication in other tissues due to exposure from primary viremia (higher concentrations of virion)
What is potential problems resulting from viremia?
spread to individuals from donated blood or from products of pooled donated blood products. (HIV)
What is neural spread?
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)
Define neurotropic
virus infects neural cells
Define neuroinvasisve
virus enters CNS after infection elsewhere
Define neurovirulent
virus can cause nervous sytem disease
What are three types of junctions that a virus may face
Basement membranes (CNS,skin, lungs, muscle)
Pores in membrane (kidney, pancreas, endocrine glands)
Sinusoids (macrophages at junction, liver spleen, bone marrow, adrenal glands)
Define incubation period
the time between inoculation and onset of disease symptoms
Difference between long or short incubation times
short: infection site is primary site for symptoms
long: host repsonse or tissue damage is not due to primary infection
Describe acute infection
rapid production of virions, infectious virus shed for short period, rapid onset of symptoms and rapid clearing of infeciton
Describe persistent infection
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
describe latent reactivating infections
initial acute infection w/periodic recurrences with or without symptoms but with infectious shedding
Describe slow virus infections
acute infection, years of continuous or periodic shedding, then symptoms preceding death
Describe inapparent acute infection
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)
Describe multiple infections of chicken pox resulting in shingles
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.
What two processes lead to antigenic drift?
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
when can antigenic shift occur?
after coinfection of two strains of virus in one cell - it can recombine or reassort
What is structural plasticity?
the ability of the virion to tolerate mutation and retain infectivity (essential for influenza, rhinovirus, HIV) Antibody resistant mutants are common in these viruses
Difference in serotypes between rhinovirus and polio?
rhinovirus maintains >100 serotypes in human population while poliovirus has 3 total. So people can get reinfected with same rhinovirus but w/different capsid
What are persistant infections
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
How does infection become persistant?
Ineffecive immune response
or infectionof cells with reduced immune surveillance
How did smallpox become eradicated?
Large scale vaccination program. Each outbreak reported to WHO and mandatory innoculation of everyone in contact w/sick person and their contacts
What are the features of an eradicable virus?
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
What are two essential features for successful global eradication
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
What are the challenges with poliomyelities eradication?
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
What livestock disease is trying to be eradicated?
Foot-and-Mouth Disease
Why haven't we eradicated more viruses?
very few meet requirements, still not well understood immunologically
What are three types of vaccines?
Attenuated, Inactivated and subunit
Problems with live attenuated vaccines?
may not induce same type of immune resonse as wild type
Problems with killed or subunit vaccines?
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
Define active immunity
adaptive immunity that is induced by natural exposure to a pathogen or by vaccination
Define passive immunity
antibodies produced in one individual placed in another
problems with passive immunity
not generally long term