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99 Cards in this Set
- Front
- Back
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characteristics of viruses (4)
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submicroscopic, obligate intracellular parasites
filterable lack "metabolism" exhibit "one-step" growth curve during lytic cycle |
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Human DNA viruses
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parvovirus
papovavirus adenovirus herpes virus pox virus |
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Human RNA viruses
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picornavirus
reovirus togavirus coronavirus orthomyxovirus rhabdovirus parmyxovirus |
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2 periods of one step growth curve
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eclipse period
latent period |
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eclipse period of virus growth curve
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time until newly assembled virus appears in the cell
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latent period of virus growth curve
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time until new infectious virus appears in medium (outside cell)
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all viruses contain what?
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nucleic acid genome
protein capsid |
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nucleocapsid
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genome & protein capsid together
all viruses have |
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other structural characteristics that some viruses have
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lipid envelope
regulatory molecules |
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virion
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entire viral particle
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enveloped virus
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nucleoplasmid + glycoproteins/membrane
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viral genomes
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5 to 200 kilobase pairs
linear or circular double or single stranded can have unusual structures, such as gapped circles |
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segmented genomes can be a characteristic of which type of virus?
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RNA viruses
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protein capsid
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1 or 2 repeated structures (helix, iscohedron)
composed of protomers (1 or more proteins) morphological units (capsomers) are usually subunits clustered around an "axis of symmetry" may also have spikes projecting from capsid surface |
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2 helical viruses
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tobacco mosaic virus
vesicular stomatitis virus |
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2 icosahedral nucleocapsids
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adenovirus
herpes simplex virus |
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viral envelope
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lipid bilayer from host cell lipids
contains virus-encoded proteins formed by budding through cellular membranes matrix proteins underlie envelope and link it to nucleocapsid |
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features used to classify viruses
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morphology
genome proteins genome organization & replication antigenic properties biological properties |
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Families of DNA viruses infecting humans
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Enveloped DNA viruses
- pox - herpes - hepadna Naked capsid - polyoma - papilloma - adena - parvo |
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+ RNA Viruses infecting humans
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Naked
- picorna - calici Enveloped - toga - flavi - corona |
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- RNA viruses infecting humans
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enveloped
- rhabdo - filo - orthomyxo - paranyxo - bunya - arena |
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+/- RNA viruses infecting humans
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double capsid - reo
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+ RNA via DNA viruses infecting humans
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retro
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steps in "model" viral life cycle
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attachment
penetration uncoating targeting gene expression gene replication virion assembly maturation release by lysis or budding |
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attachment step of viral life cycle
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interaction btw specific viral attachment protain (VAP) and cell surface receptor
VAP always on virus surface (capsid or envelope) glycoprotein or glycolipid |
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attachment protein interactions determine what?
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host range
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penetration step of viral life cycle
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penetration of host cell by one of 2 mechanisms:
receptor mediated endocytosis direct membrane fusion |
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uncoating and targeting step of viral life cycle
3 options: |
* genome completely released from capsid during or after penetration ("uncoating")
* 1st stages of virus replication occur inside partially uncoated capsids * most DNA viruses are targeted to nucleus of host cell where repl. & t/sc occur |
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Baltimore classification
Class I |
double stranded DNA
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Baltimore classification
Class II |
single stranded DNA
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Baltimore classification
Class III |
double stranded RNA
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Baltimore classification
Class IV |
postive strand RNA
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Baltimore classification
Class V |
negative strand RNA
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Baltimore classification
Class VI |
retrovirus
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Gene expression and replication of DNA viruses
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nucleocapsid or genome targeted to nucleus (except Pox)
viral early genes expressed - t/sc in nucleus using host RNA polymerase & TFs --> early mRNAs early mRNAs --> cytoplasm - t/sl into early proteins (usu. enzymes or regulatory proteins required for duplication) |
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What happens to early proteins of DNA viruses
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targeted to nucleus for use in viral DNA replication
- also requires host cell enzymes after viral genome replication, late genes are t/sc & t/sl |
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what proteins constitute late proteins of DNA viruses
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capsid, matrix and envelope proteins
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which proteins are often present at very high levels in cells infected with DNA viruses?
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late proteins
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Parvovirus variation of DNA virus replication strategy
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contain ssDNA genome
must be converted to dsDNA before t/sc |
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Large DNA virus (e.g.: herpes virus) variation on replication strategy
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additional stages of gene expression,
including immediate early, early and late |
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Poxvirus variation on DNA virus replication strategy
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replicate in cytoplasm
encode all proteins needed for own gene expression and replication |
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4 general characteristics of RNA virus replication
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most replicate entirely in cytosplasm
encode own replicases (since host cells do not contain RNA dependent RNA polymerases) generally have high mutation rates b/c RDRPs have no proofreading function have high levels of recombination |
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replication and gene expression of + strand RNA viruses
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+ strand indicates that genome can serve as mRNA and be directly t/sl into proteins
purified RNA from these viruses can therefore be infectious (i.e.: proteins not required) |
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+ strand replication steps
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viral proteins (incl. replicase) are t/sl directly from viral RNA
viral replicase then synthesizes the complementary - strand from the + strand the - strand is used as a template to make addl + strand newly synthesized + strand can be used in several ways |
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newly synthesized + strand uses (3)
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produce addl viral proteins
produce additional - strand be packaged into virions |
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replication and gene expression of - strand RNA viruses
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genome of these viruses cannot be used as a template for protein synthesis
viruses must bring replicase in virion |
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replication steps of - strand RNA viruses
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viral - strand used as template to synthesize + strand, using virion associated replicase
+ strands (mRNA) are t/sl --> proteins, incl. addl replicase + strands used as templates for new - strands |
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replication straetgies for double stranded RNA viruses
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t/sc of viral genome gives rise to early mRNA (ririon associated transcriptase)
t/sl of ealy mRNAs --> early proteins replication of viral genome & synthesis of late mRNAs t/sl of late proteins packaging of new viral genomes |
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enveloped viruses require what for infection/transmission?
why? |
require direct contact via blood, aerosols, etc.
b/c sensitive to desiccation, extreme pH, detergent, etc. |
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infection/transmission characteristics of non-enveloped viruses
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can survive relatively long times outside body
indirect transmission enteroviruses can withstand acidic environment of stomach |
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primary viremia
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entry of virus into bloodstream and spread throughout body
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secondary viremia
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replication in 2* target organs (liver, spleen, bone marrow, etc.)
infection of final target tissue (brain, etc.) |
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final pathway of virus spread
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release/shedding of virus
(skin, slaiva, resp secretions, genital secretions, fecal/oral, blood, transplacental) |
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permissive cell
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cells in which a virus can replicate
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2 fates of persistent viral infections
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constant shedding (HIV)
latent (HSV) |
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5 mechanisms of pathogenesis
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direct cell killing
direct infection of immune cells indirect effects on immune system immunopathology (inflammation, etc.) oncogenic transformation |
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diagnosis of viral disease (5 modalities)
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presence of anti-viral Abs
presnece of viral protein or particles presence of viral nuclei acid cytological examination of tissue virus isolation |
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size of IFN-alpha & -beta
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20 kDa
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virally infected leukocytes are induced to synthesize what cytokine?
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IFN-alpha
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virally infected fibroblasts/epithelial cells are induced to syntheisze what cytokine?
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IFN-beta
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one signal that induces IFN synthesis
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dsRNA
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antiviral state
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binding of IFN to cell receptor results in activation of up to 100 genes in attempt to interrupt viral life cycle
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Pkr
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dsRNA-activated protein kinase
induced in inactive form in reponse to IFN tx of uninfected cell if cell subsequently infected by virus & accumulates dsRNA, Pkr activated |
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what does activated Pkr phosphorylate?
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elF2a translation initiation factor
phosphorylated eIF2a --> inhibition of translation leads to block of both viral & cellular protein synthesis |
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RNase L
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ribonuclease
synthesized in response by IFN tx activated by oligo-A degrades viral and cellular RNAs |
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2'-5' oligoA synthase
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enzyme
induced by IFN activated by dsRNA synthesizes oligoA |
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2 enzymes that inhibit viral replication
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RNaseL
Pkr |
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3 general features of IFN action
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Pkr & RNase L block cell & viral gene expression
- so long-term activation of IFN-activated genes --> PCD generally, RNA viruses induce IFN response more efficiently than DNA viruses many viruses evade IFN effects |
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2 virus types that evade IFN effects
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influenzavirus
adenovirus |
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humoral immune system is primarily effective against what stage of the virus life cycle?
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extracellular
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What type of antibodies prevent virus from entering and/or replicating in host cells?
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neutralizing antibodies
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3 mechanisms of neutralizing viruses
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Ab-coating enhances phagocytosis (opsonization)
enveloped viruses coated w/ Ab can by directly lysed by complement virus infeccted cells coated with Abs can be lysed by complement or killed by NK cells via ADCC |
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limits to humoral immunity
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not as effective late in infection since Ab does not effectively see intracellular virus
Abs alone not sufficient - requires cellular immune system |
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CTL cell killing is (4 characteristics)
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Ag specific
self-restricted requires cell-to-cell contact CTL cells not killed in process, so can act more than once |
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What cells express MHC class I?
What cells express MHC class II? |
all nucleated cells = MHC class I
APCs = MCH class II |
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5 reasons for immune system failure
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in very acute infections, immune system does not have time to respond
viral evasion strategies infection of cells that do not normally express class I MHC (e.g.: neurons) decreasing expression of CAMs required for effecient CTL/target cell interaction killing or suppression of immune cells |
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goals of immunization (3)
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elicit synthesis of neutralizing Ab - block early stages of subsequent infections
subsequent infections will elicit 2* immune response (stronger & more rapid) bbreak cycle of infection/spread, so that specific viral ds can be eliminated from the population |
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Desired characteristics of vaccines (4)
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safety
effectiveness stability (long-term storage) affordability |
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5 characteristics of attenuated live viral vaccines
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can use related but non-pathogenic virus or attenuated strains of virulent virus
stimulate both humoral and celluilar immune system, and confer long-term immunity natural route of infection; can induce secretory immunity can cause ds, esp. in immunocompromised can revert to virulence |
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examples of attenuated live viral vaccines
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Sabin polio vaccine
Measles Mumps |
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4 characteristics of killed/inactivated viral vaccines
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virus inactivated by chemical or phycisal procedures that eliminate infectivity w/o destroying antigenicity
require adjuvants & multiple doses inefficient at inducing cellular immune response and long-term immunity safe: minimal side effects |
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examples of killed/inactivated viral vaccines
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Salk polio virus
influenza rabies |
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3 characteristics of subunit vaccines
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purified viral proteins used as immunogens (usu. produced via recombinant DNA methods)
protein chosed as immunogen should induce neutralizing or protective Abs has many of same advantages and disadvantages as killed viral vaccines |
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4 characteristics of recombinant viral vaccines
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gene encoding viral Ag that is target of neutralizing Abs is combined into non-virulent viral vector so that expressed dur. viral infection
adv/disadv similar to attenuated virus, but less danger of reversion/disease may be possible to produce recombinanats that protect against several viruses method under development |
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4 characteristics of DNA based vaccines
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DNA encoding specific viral proteins injected directly into muscle or skin & taken up into cells, which express viral proteins
cellular immune response stimulated - long term immunity possible safe (no infectious agent) inexpensive and stable |
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current attenuated viral vaccines
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Sabin oral polio vaccine
Measles Mumps Rubella Varicella-zoster Adenovirus Yellow fever Smallpox |
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current inactivated viral vaccines
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Salk polio vaccine
Influenza Hep A Rabies Japanese Encephalitis Eastern Western Russion encephalitis viruses |
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current subunit viral vaccines
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Hep B virus
human papilloma virus |
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2 limits of vaccination
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difficult to develop for some viruses
usually not effective after infection |
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goal of antiviral drugs
difficulty |
goal: find drug that inhibits viral replication w/o harming human host
difficulty: most viruses use human proteins during life cycle |
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experimental antiviral durgs that block attachment receptors
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peptide derived from gp120 or cellular CD4 receptor
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antiviral drugs that neutralize pH of endosomes
effect of pH neutralization |
hydrophobic amines:
- amanatine - rimantadine neutralizing endosome pH blocks viral uncoating |
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specific effects of amantadine & rimantadine against influenza
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block channel formed by influenza M2 protein
thereby blocking H+ influx, uncoating & translocation of nucleocapsid to the nucleus |
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drugs that block uncoating of picornaviruses by fitting into cleft in the receptor binding canyon of the capsid
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arildone
disoxaril pleconaril other methylisoxazole |
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nucleoside analogues can have modification to ____, ____ or _____
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base, sugar, or both
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mechanism of nucleoside analogue mediated inhibitors of viral replication
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incorporated into DNA, where they either
- cause chain termination due to the absence of a 3'- OH - alter base pairing --> transcription errors |
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to be effective, nucleoside analogues must have...
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specificity for viral over cellular enzymes
- to limit possible side effects |
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Additional classes of antiviral drugs
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non-nucleoside polymerase inhibitors
antisense oligonucleotides protease inhibitors (HIV) interferon |
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3 limits of antivirals
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potential side effects b/c of incomplete specificity
development of resistance, esp. w/ RNA viruses and retroviruses due to high mutation rates tx w/ multiple drugs decreases emergence of resistant mutants |
