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97 Cards in this Set
- Front
- Back
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characteristic sturcture of enveloped viruses
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nucleocapsid
coated with a lipoprotein membrane (w/ lipid derived from host cell membrane, and often spike-like projections of glycoprotein on |
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what destoys the infectivity of enveloped viruses
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treatment wtih ether, does not harm polio or any other simple nucleocapsid viruses
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characterize the stability of enveloped viruses
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generally unstable, transmission requires close contact
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characterize assembly pattern of enveloped viruses
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more complicated than that of unenveloped viruses
-few cell-associated virions at any time -continuous release of virions w/o gross cellular damage (cell may ultimately die) -use of a modified cellular membrane -viral envelope acquired from hotel cell membrane as virus exits cell via "budding" process |
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characterize the cell membrane of enveloped virus
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contains viral glycoprotein spikes
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antigens for neutralizing antibody on enveloped viruses
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envelope glycoproteins
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antigens for neutralizing antibody on
unenveloped viruses |
nucleocapsid protein
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what kind of viruses are sensitive to ether?
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enveloped viruses
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how are unenveloped viruses released from infected cells?
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lysis
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how are enveloped viruses released from infected cells?
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budding
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orthomyxoviruses- (nucleocapsid structure)
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enveloped (composed of lipid as well as viral glycoproteins)
8 helical nucleocapsids |
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orthomyxoviruses- (virion nucleic acid)
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8 segments of single (-) stranded RNA
(each RNA segment has genetic info to encode at least one unique viral protein product) |
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what type of RNA viruses have RNA polymerase in their virion
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(-) stranded RNA viruses
double-stranded RNA viruses |
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viral antigens of orthomyxoviruses
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virion envelope membrane antigens = viral gylcoproteins
Hemagglutinin (H) Neuramidase (N) |
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Hemagglutinin (H)
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H glycoprotein
-fxns early in the infection of a cell -required for absorption of virions to host cells - primary target for neutralizing antibody |
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Neuraminidase (N)
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N-antigen/ N-glycoprotein
-enzyme that fxns late in the infection of the host cell -enzyme fxn to release newly formed virions from infected cell surface by cleaving sialic acid bonds -cleavage allows newly formed virus to: infect new cells be sneezed or coughed to infect a new host and initiate a new infection |
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Ab to hemagglutinin
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neutralize orthomyxovirus virions
most important in controlling orthomyxovirus infection |
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Ab to neuramiinidase
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does NOT nuetralize orthomyxovirus virions
however, it does: - slow down the release of newly formed virions -slows down infection in the infected individual -reduces the severity of the disease -reduces the likelihodd that the infection will spread to a new individual HOWEVER Ab TO HEMAGGLUTININ IS MORE IMPORTANT (can neutralize virions and block infection of new cells) |
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Mechanism of orthomyxoviruses
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agglutinate red cells (HEMAGGLUTINATION)
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HEMAGGLUTINATION
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agglutination of red cells
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how is relative concentration of orthomyxovirus virion measured in a clincial sample?
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hemagglutination can be used
(does not require that virions be infectious, only that hemagglutinin (H), the H-antigen, be present and functional in the envelope of virions. |
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HEMAGGLUTINATION INHIBITION
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inhibition of hemagglutination
can be used to titrate the relative concentration of antiviral Ab in serum samples |
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Why can't RBCs support a productive virus infection?
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they do not synthesize RNA or proteins
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How do RBCs interact with orthomyxoviruses
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RBCs possess the surface receptor that bind the H-antigen
explains basis for hemagglutination |
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PANDEMIC of 1918-19
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world-wide epidemic of Influenza
30-50 million deaths |
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How are minor epidemics detected
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calculated of excess mortality (above expected for influenza-pneumonia)
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Types of Human Influenza
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influenza A
influenza B influenza C |
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different influenza strains within each type of influenza are based on:
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antigenic differences in the hemagglutinin and neuraminidase
as well as genetic variation in polymerase genes and other genes encoded by the influenza virus |
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annual influenza vaccine usually includes:
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2 different influenza A strains that are anticipated to represent the predominant H-antigen and N-antigen types of the current flu-season
and one influenza B strain |
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Influenza A
minor epidemics every.. major epidemics (pandemics) every.. |
minor, 2-3 years
major 10-30 years |
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influenza is an example of what type of virus?
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orthomyxovirus
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what causes minor epidemics?
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ANTIGENIC DRIFT: minor variation by mutation within existing RNA segments yield a minor epidemic
a different minor antigenic varient of the H-antigen is responsible for each epidemic wave. exisiting antibody in the human population from previous epidemics confers partial immunity. |
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ANTIGENIC DRIFT
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Minor antigenic variation
caused by mutations in the gene for the H-antigen |
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what causes major pandemics?
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when existing Ab in the human population from previous epidemics fails to confer any immunity.
all pandemics result from ANTIGENIC SHIFT (major antigenic variation of the H-antigen) |
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what is always shifted in pandemic strains of influenza A?
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H glycoprotein antigen is always antigenically shifted
N glycoprotein is sometimes shifted as well (usually makes pandemic worse, bc patients lack both the neutralizing Abs to the H antigen) as well as the severeity reduction effects of Ab specific for the N-antigen. |
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ANTIGENIC SHIFT
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major change in H-antigen
results in pandemic mechanisms: 1) GENETIC RECOMBINATION bt human and animal influenza A viruses 2) DIRECT TRANSMISSION OF ANIMAL VIRUS TO HUMAN POPULATION (rare) |
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ANTIGENIC DRIFT
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minor mutation in H-antigen
causes minor epidemic, due to partial immunity |
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requirements for genetic recombination between two closely related viruses
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two viruses must:
infect the SAME CELL at more or less the SAME TIME |
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why is viral recombination rare in polio virus?
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VIRAL NUCLEIC ACID IS ALL IN ONE PIECE
when 2 parental viruses infect the same cell, each RNA molecule replicates separately progeny RNA molecules are then randomly assembled into virions Recombination is rare or absent because it REQUIRES BREAKAGE and REUNION of the viral RNA molecules (like xing over in classical genetics) |
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how is viral recombination detected?
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using genetic markers
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why is viral recombination more prevalent in influenza viruses?
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VIRAL NUCLEIC ACID IS IN MULTIPLE PIECES
Two parental viruses infect the same cell Each nucleic acid molecule replicates independently The progeny RNA molecules are then randomly assembled into virions In this case (if there are 2 nucleic acid molecules/ parental virion) about 1/2 the progeny virions are recombinant HIGH RECOMBINATION is due to random REASSORTMENT (rather than crossing over required in single molecule recombination) |
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REASSORTMENT
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one of 2 mechanisms of genetic recombination in viruses. (e.g. the recombination of RNA molecules from different Influenza A viruses infecting the same cell, resulting in a new Influenza A virus strain)
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what contributes to recombination of viruses?
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-2 similar viruses infect same cell around same time
-viral genome composed of multiple segments of RNA (reassortment = recombination) |
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examples of viruses with high level of recombination
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those with segmented genomes, eg:
rotaviruses (mult. segments, double stranded RNA) orthomyxoviruses (8 segments (-) stranded RNA) |
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PHENOTYPIC MIXING
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non-genetic interaction, whereby virions are assembled from randomly chosen components (of DIFFERENT closely related viruses)
e.g. Polio type I and type 2 cell infected by both viruses potential virions assembled with Type I RNA: a) All type 1 capsomers, Type I RNA b) All type 2 capsomers, Type I RNA c) A mixture of type I and type 2 capsomers, Type I RNA b&c phenotype of virion does not correspond to genotype of the RNA, but only transient because progeny will have only Type I capsomers and type I RNA |
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lab diagnosis of influenza
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virus isolation in:
embryonated eggs or tissue cultures or comparision of acute and convalescent sera, looking for a rise in antihemagglutinin (anti H) Ab by the hemagglutination inhibition assay. rapid diagnosis, uses fluorescent Ab on a throat swab specimen |
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influenza virus transmission
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person-to-person by coughts and sneezes
droplets initially infect the upper respiratory tract and the infection often extends to the lower respiratory tract |
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symptoms characteristic of influenza
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fever, chills and aches
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pathogenesis of influenza
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virus directly enters the respiratory tract (mucosal surface)
infects cells and and launches infection at the sight of virion entry causing: destruction of ciliated epithelium in the respiratory tract toxic components released from the sites of local growth in the respiratory tract cause systemic symptoms (headache, muscle pains) viremia is NOT common , does NOT play role in pathogenesis |
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most common complication of influenza
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pneumonia, sometimes with secondary bacterial infection:
- pneumococcus (most common) - staphylococcus (most of the fatal cases) bacterial pneumonia due to destruction of ciliated epithelium and malfunctioning infected alveolar macrophages |
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why is pneumonia a common complication of influenza infection?
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influenza results in the destruction of ciliated epithelium in the respiratory tract
the absence of this innate immune mechanism and the malfunctioning of infected alveolar macrophages leads to increased susceptibility for pneumococcus infection. |
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influenza is most fatal in what population(s)?
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elderly (65+)
as well as infant population |
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what underlies most influenza caused death?
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respiratory insufficiency (COPT, etc..)
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Influenza (Immune response)
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no obligatory viremia, therefore short incubation period (days)
bc infection attacks the respiratory tract, immunity is largely dependent upon secreted IgA immunity is less effective than immunity in viremic diseases and may be short-lived (3-10 years) disease caused by re-infection is generally milder than the primary infection |
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most important factor in immunity to (and in recovery from acute) Influenza infection
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SECRETED IgA in UPPER RESPIRATORY TRACT
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Influenza Vaccines
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polyvalent formaldehyde killed injected vaccine
(typically: Two H-antigen variants of type A influenza and one type B strain) *new virus isolates added each year to update the vaccine ~70% effective |
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efficacy of killed Flu Vaccine
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~70%
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problems with killed flu vaccine
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will not efficiently induce secreted IgA
induces an IgG response and IgG Abs that are sub-optimal for protection |
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who gets killed influenza vaccine?
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special risk groups
everyone over age 50 medical personnel (esp. those caring for elderly population) infants young pediatric age group (can be used in all age groups) |
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FluMist
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polyvalent (several A and B strains) live-attenuated influenza vaccine
administered by intra-nasal spray selected for optimal growth at low temperature, grows poorly at body temperature efficacy ~ same as killed vaccine only approved for age 5-49 (THOSE LEAST LIKELY TO DIE FROM INFLUENZA VIRUS) |
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Treatment for Influenza
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Influenza A infections (ONLY A) can be prevented or treated with drugs:
AMANTADINE or RIMANTADINE Drugs active against both A & B: oseltamivir (Tamiflu) and zanamivir (Relenza) **both inhibit neuraminidase activity, |
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AMANTADINE
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drug used to prevent/treat influenza A
tricyclic amine, probably blocks late phase of the absorption-penetration-uncoating process NARROW SPECTRUM (ONLY A) more effecitve if given before infection not markedly toxic to patients (human's don't have biochem fxn analogous to penetration-uncoding step of influenza A growth) |
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Tamilflu and Relenza
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drugs active against influenza A and influenza B
if given w/in 48 hours of infection... inhibit neuraminidase activity: slows down the release of virus from infected cells, slows cell-to-cell spread of virus, reduce symptomatic period |
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Paramyzoviruses (virion characteristics)
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1 molecule
single (-) stranded RNA helical nucleocapsid |
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Similarities between paramyxo and orthomyxo virions
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minus-stranded RNA (complementary to mRNA)
RNA polymerase present in the virion |
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Examples of paramyxoviruses of humans
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mumps and measles (cause systemic infections with viremia)
non-systemic respiratory disease: parainfluenza virus (4 types) Respiratory Syncytial Virus (RSV) |
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Characteristics of non-systemic paramyxoviruses (4 types of parainfluenza virus and RSV)
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a) no major shifts in antigenicity
(1 molecule of RNA, vs. major shifts in viruses with multi-segmented genomes) b) many subclinical infections c) severe, febrile, lower respiratory infection only on initial (childhood) infection. Infection does NOT result in life-long immunity. Thus, adult infections are relatively common, but generally less severe d) virions agglutinate red cells and the hemagglutination tests are useful |
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Croup
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(acute laryngo-tracheo-bronchitis)
characterized by dyspnea and stridor (high pitched, noisy inspiration) |
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Croup (population affected)
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primarily a disease of the first 3 years of life, with a peak incidence at age 2
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Croup (most common cause/ virus type)
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Parainfluenza viruses, which are Paramyxoviruses
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Croup (treatment)
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gluccocorticoids can be used to treat severe cases
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Respiratory Syncytial Virus (virus type)
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paramyxovirus (non-systemic)
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Respiratory Syncytial Virus (population affected)
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most frequent cause of severe lower respiratory infection in infants
recently recognized as significant infection of the elderly population (IgA doesn't provide good long-term immunity) |
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Respiratory Syncytial Virus (treatment)
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chemotherapy with aerosolized ribavirin, uncertain efficacy
used with high-risk patients and in severe infections passive immunization of high risk infants (premature, pulmonary displasia, etc.) with high doses of monoclonal Ab against RSV (palivizumab) is effective in preventing severe RSV pneumonia no vaccines are available |
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SARS (caused by what type of virus?)
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SARS-associated coronavirus
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SARS (disease characteristics)
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SEVERE ACUTE RESPIRATORY SYNDROME
serious lower respiratory tract infection, dry cough and dyspnea |
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SARS (nucleocapsid struture)
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enveloped
single molecule (+) stranded RNA helical nucleocapsid |
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SARS (transmission)
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transmitted by respiratory droplets (maybe other pathways)
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SARS (incubation period)
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incubation period 2-10 days
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SARS (population affected)
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nearly all cases in adults,
severity increasing with age |
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SARS (case-fatality rate)
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~9%
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SARS (origin, epidemiology)
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first appeared in China
rapidly spread world-wide by international air travel effective case-finding, isolation or quarantine may have halted this epidemic |
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protein classes involved in the interferon system
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interferons
and virus inhibitory proteins |
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function of the interferon system
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suppresses viral growth
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interferons
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proteins, newly synthesized and secreted into EC fluid by:
- virus-infected cells (secrete alpha and beta interferons) and - antigen-stimulated T cells (secrete gamma interferon) |
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when are interferon and virus inhibitory proteins synthesized?
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AFTER viral infection
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virus inhibitory proteins (+ important examples)
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proteins synthesized by UNINFECTED CELLS when their plasma membrane interferon receptors bind interferon molecules
IMPORTANT EXAMPLES: - 2-5-A synthase - a specific protein kinase |
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How does a cell "know" that it is infected by a virus and thus should produce interferon that will protect other cells in the body?
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GOOD QUESTION!???
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what do virus-inhibitory proteins do?
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block protein synthesis
w/o protein synthesis, an infected cell cannot produce progeny virions |
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2-5-A Synthase
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an enzyme that synthesizes 2-5-A (a short polynucleotide)
2-5-A activates a ribonuclease that DESTROYS mRNA, thus inhibiting protein synthesis |
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A specific protein kinase
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one of the virus inhibitory proteins:
inhibits protein synthesis by: specifically phosphorylating initiation factor 2, which is essential to start the process of protein synthesis phosphorylated initiation factor is not active, thus protein synthesis is inhibited |
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toxicitiy of interferon to uninfected cells
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relatively non-toxic because:
both virus inhibitory proteins are inactive, until the interferon-treated cell becomes infected |
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what kind of affect do different viruses have on interferon production
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interferon is a CELLULAR PRODUCT
interferon is unrelated to the virus that induces its synthesis the same interferon is produced by a cell infected with a vairety of viruses SOME VIRUSES ARE BETTER INDUCERS than others |
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specificity of interferon protection
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interferon shows species specificity in protection
it will protect cells only from the same species that produced it (bc interferon receptor binds only interferons of its own species) interferon DOES NOT show viral specificity: a variety of viruses (DNA or RNA) are inhibited, although their sensitivity to interferon may vary |
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INTERFERON:
(cells protected by it) (viruses affected by it) (mechanism of action) |
cells protected: only the species that produced it and related species
viruses affected: any virus mechanism: blocks protein synthesis in infected cells by via induction of synthesis of virus inhibitory proteins |
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ANTIBODY:
(cells protected by it) (viruses affected by it) (mechanism of action) |
cells protected: any species
viruses affected: only the virus that induced it mechanism: neutralizes extracellular virions by blocking adsorption and penetration |
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compare timeframes of interferon and Ab production
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interferon production: TRANSIENT (appears several days after infection, peaks ~ day 14, gone a few days after that
neutralizing IgG: made for life neutralizing IgM: declines in a few months |
