Block 11 - L1-2 Flashcards
Viruses are small, ___ (2 descriptors) parasites. They pass through ___ that retain bacteria.
Obligatory intracellular
Viruses are true parasites - what does this mean?
They contain no mitochondria, ribosomes, or other cellular organelles of their own. They depend entirely on the machinery of the host cell for their energy production and protein synthesis.
True or false - like bacteria, viruses grow on nutrient media
False - viruses do not grow in nutrient media.
All cells or microorganisms contain both DNA and RNA - the repository of the genetic material is the ___. Viruses have either DNA or RNA, but never both. What is the genetic material in a particular virus?
DNA; Nucleic acid present in the virus
How do viruses respond to antibiotics and why?
They are not sensitive to antibiotics because their metabolism is completely dependent on the host cell.
___ can be induced and inhibit viral replication. Some viruses can block this induction.
Interferon
Viruses vary tremendously in shape and size, but all viruses are composed of what two essential components?
Protein and nucleic acid (some viruses also contain lipid membranes surrounding the nucleic acid)
The standard viral classification system is by the ___.
Viral genetic information (genome)
Discuss some of the categorical features of the viral genome.
- RNA or DNA
- RNA positive or negative
- Single or double-stranded
- Non-segmented or segmented
- Molecular weight
What is a positive-sense single-strand of RNA?
Can be translated directly into protein (equivalent to mRNA)
What is a negative-sense single-strand of RNA?
Cannot be translated directly into protein; must first be transcribed into mRNA; viruses with this RNA must carry their own enzyme for transcription
What is the suffix for the family of a virus? The genus? The species?
Family: -viride (Paramyxoviridae)
Genus: -virus (Morbillivirus)
Species: vernacular (Measles)
List the 1 double-stranded (segmented) RNA viral families.
Rotavirus
List the 6 positive single-stranded RNA viruses.
- Picornavirus (nonenveloped)
- Norovirus
- Togavirus
- Flavivirus
- Coronarvirus
- Retrovirus
List the 6 negative single-stranded non-segmented RNA viruses.
- Paramyxovirus
- Measles
- Mumps
- RSV
- Rhabdovirus
- Rabies virus
List the 4 negative single-stranded segmented RNA viruses.
- Orthomyxovirus
- Influenza
- Arenavirus
- Bunyavirus
List the 2 single-stranded DNA viruses (circular and linear).
- Some bacterial viruses (circular)
2. Parvovirus (linear)
List the 5 double-stranded DNA viruses (circular and linear).
- Polyomavirus (circular)
- Papillomavirus (circular)
- Adenovirus (linear)
- Herpesvirus (linear)
- Poxvirus (linear)
What is the partly single-stranded DNA virus?
Hepatitis B virus (RNA intermediated in replication)
List the stages of viral replication and infection.
- Attachment (virus proteins bind to plasma membrane receptor)
- Penetration (taken up in coated pits to form vesicles)
- Uncoating (virus envelope fuses with endosome membrane at low pH)
- Transcription (viral mRNA synthesized)
- Translation (viral mRNA translated into proteins)
- Replication (specific for each type of genome)
- Assembly
- Release (enveloped viruses bud through the cell membrane)
What happens in the innate immune response to viruses?
Interferon synthesis is induced by viral infection. It induces anti-viral states (new protein production) in neighboring, uninfected cells.
What are the ultimate effects of interferon?
Inhibition of protein synthesis and viral replication
Via what two pathways does interferon inhibit protein synthesis?
- Production of 2-5A synthetase, which activates RNAase L to destroy mRNA
- Production and activation of a protein kinase that phosphorylates eIF2 (initiation factor required for protein synthesis) leads to inhibition of translation
Detection of ___ specific to the virus during the acute stage of illness is frequently used in diagnosis. Detection of ___ specific to the virus is a good indicator of previous exposure to the virus.
IgM; IgG
In addition to antibodies, what is another important part of the adaptive immune response to viruses?
Killer T cells (cell-mediated immunity is very important in the control of latent viral infections)
___ block activation or action of Type I interferons. Other viral proteins, termed ___ and ___, block host cytokines that promote the adaptive response.
Viral interferon antagonists; virokines; viroceptors
What are some of the pathogens included in the family, picornaviridae?
- Enteroviruses (poliovirus, enteroviruses, hepatitis A virus, coxsackie A and B viruses, echoviruses)
- Rhinoviruses
What are some of the unique properties of poliovirus?
Icosahedral capsid enclosing a single-strand positive RNA genome
3 serotypes
Replicates in the cytoplasm, genome acts as mRNA
Cytolytic
Resistant to pH 3.0-9.0, mild sewage treatment, temperature
What is the reservoir of poliovirus?
Humans (only)
What is the transmission pattern of poliovirus?
Fecal-oral
What is the temporal pattern of poliovirus?
Summer-fall in temperate areas; no pattern in tropics
Describe the communicability and incubation period of poliovirus.
Communicability - 7-10 days before onset, virus present in the stool for 3-6 weeks
Incubation period - 6-20 days (ranges from 3-35)
Describe the pathogenesis of poliovirus.
Invades via the intestinal mucosa and multiples/infects the underlying lymphatic tissue; it is also excreted in the feces. In the absence of Ab, it spreads by viremia to cells of a receptor-bearing target tissue (anterior horn cells).
Note - viral pathology is usually responsible for disease symptoms (not immune response).
What are the four possible outcomes of poliovirus infection?
- Asymptomatic (90-95% - results if limited to the oropharynx and the gut)
- Abortive poliomyelitis (4-8% - minor illness, no CNS involvement, non-specific, fever, headache, malaise, sore throat, vomiting; complete recovery)
- Non-paralytic poliomyelitis or aseptic meningitis (1-2% - back pain, muscles spasm + minor illness symptoms)
- Paralytic poliomyelitis (0.1-2% - most severe outcome, spinal paralysis of 1+ limbs, bulbar paralysis may involve a combination of cranial nerves and even the medullary respiratory center; usually asymmetric, sensory intact)
Poliovirus is primarily an ___ virus which occasionally invades the ___.
Enteric; CNS
List the ways poliovirus infection is detected and what is used currently in modern medicine.
Virus isolation from throat swabs
Isolation from multiple fecal samples
Serology
Now - RT-PCR and sequencing
What are the two types of poliovirus vaccines? Compare them.
- Salk virus - inactivated poliovirus (all three serotypes); administered intramuscularly, little to no duodenal IgA generated
- Sabin vaccine - live, attenuated vaccine (all three serotypes); administered orally, induces good duodenal IgA response
What are the AE of oral poliovirus vaccine?
Paralytic poliomyelitis (more likely in immunodeficient persons, no procedure available for identifying persons at risk of paralytic disease) Death from paralytic disease
What is the current recommendation for vaccination against polio?
3 dose regiment - IPV (first vaccination), IPV (first boost), IPV (second boost)
The mechanism of action of interferon involves:
A. Induction of enzymes to degrade mRNA and inhibit protein synthesis
B. Upregulation of the immune response to viral antigens
C. Stimulation of the cycle to cause cells to divide before they are infected
D. Shutdown of splicing activity in the virus infected cells
E. Killing of virus infected cells by NK cells
A - induction of enzymes to degrade mRNA and inhibit protein synthesis
What are two potential problems with OPV?
- VAPP (vaccinee and household contacts are at risk)
2. Shedding of revertant viruses (revertants in fecal material may contaminate local water supply)
Why is elimination of poliomyelitis by vaccination theoretically possible?
Humans are the only natural host for poliovirus
Which patient population should never receive a live polio vaccine?
Immunocompromised individuals
What are the advantages and disadvantages of the oral polio vaccine?
Advantages - effective, lifelong immunity, induction of secretory Ab, spread of attenuated virus circulating to contacts promotes herd immunity, inexpensive/easy to administered, no need for booster
Disadvantages - risk of VAPP in recipient or contacts, spread of vaccine to contacts without their consent, not safe in immunodeficiency
What are the advantages and disadvantages of the inactivated polio vaccine?
Advantages - effective, good stability during transport/in storage, safe in immunodeficiency, no risk of VAPP
Disadvantages - lack of induction of secretory Ab, booster needed for lifelong immunity, requires sterile syringes/needles, injection is painful, higher community immunization levels needed
What is the most common outcome after infection with poliovirus?
Asymptomatic infection
How is poliovirus transmitted?
Fecal oral
How is infection by poliovirus detected?
Detection of viral sequences by RT-PCR
What is the mechanism/pathogenesis of poliomyelitis?
Lytic destruction of anterior horn cells
Are there any anti-viral therapies for treating poliovirus-infected patients?
No
Are there any vaccines to prevent poliomyelitis?
Yes - live-attenuated oral vaccine and killed-virus injected vaccine
Are there any long-term consequences associated with poliovirus infection?
Long-lived protective immunity
What are some clinical syndromes associated with enteroviruses?
- Aseptic meningitis
- Pericarditis and myocarditis
- Exanthems
- Muscle weakness/paralysis
- Conjunctivitis
How are enteroviruses diagnosed in the lab?
RT-PCR
Which enterovirus serogroup is transmitted via respiratory secretions (exception - usually fecal-oral)?
EV-D68
What drug exhibit anti-viral activity against multiple members of the picornavirus family (under development, not FDA-approved, can be used in emergencies) and how does it work?
Pleconaril; binds to a hydrophobic pocket of the virion coat protein while viral particles are being assembled. The shape of the receptor binding canyon is altered and the virion is unable to attach to a receptor and infect a new cell.
Describe the route of transmission of Hepatitis A.
Transmitted via the fecal-oral route; common sources of contamination are shellfish, food handlers, and daycare centers
Discuss the pathogenesis of Hepatitis A (incubation period, symptoms, course, etc.).
Incubation period: 15-45 days
Acute onset of fever, malaise, anorexia, headache, nausea, vomiting
Clinical jaundice, hepatomegaly, dark urine
ALT is elevated for 5-10 days prior to onset of jaundice and may persist for 2-6 weeks
Self-limiting, non-fatal
How is Hepatitis A diagnosed?
Clinical presentation alone is not a reliable diagnosis; during acute infection, anti-HAV IgM is detected in the serum. HAV particles and/or antigens are detectable by immunoassay of the feces.
Discuss the HAV vaccine.
Inactivated HAV, very effective (even post-exposure)
Initial intramuscular injection, booster dose in 6-12 months
Travelers to countries with high or intermediate endemicity of infection, children in high risk communities, sexually active homosexual men/others with high risk sexual behavior, people with chronic liver disease (especially Hepatitis C), and others who have occupational risk
List the most common viral causes of diarrhea.
- Rotavirus
- Norovirus
- Astrovirus
- Adenovirus
- Coronavirus
(75-80% of cases of acute diarrhea are of viral origin)
What is the primary manifestation of rotavirus and how is it transmitted?
Epidemic diarrhea of young children (dehydration, vomiting, fever, diarrhea); human contact
How does rotavirus appear on EM?
Wheel-like
How is rotavirus detected?
Viral particles can be readily detected in a stool sample via ELISA/EIA due to the large number of virus particles excreted; some clinical labs are now using film array PCR
What is the temporal pattern of rotavirus?
Winter (November to April), spreads across the US from west to east over this time period
Discuss the pathogenesis of rotavirus.
Infection primarily restricted to the villus epithelium of the SI; previously, we thought malabsorption secondary to destruction of enterocytes results in osmotic diarrhea; now, we think rotavirus encodes a viral enterotoxin (NSP4), which causes the diarrhea
How does NSP4 cause diarrhea?
Mediates acquisition of a transient membrane envelope as subviral particles bud into the ER, mobilizing release of Ca2+ from internal stores
Discuss the vaccine for rotavirus.
Rotateq - pentavalent live-attenuated vaccine
Rotarix - live-attenuated
Antibodies to which components of the rotavirus are neutralizing?
VP4 and VP7
Reassortment occurs in which two viruses?
Rotavirus and influenza virus
Which type of viral genome can undergo reassortment?
Those with segmented RNA genomes (can undergo reassortment if multiple viruses infect the same cell)
What is the most common cause of non-bacterial acute epidemic diarrhea?
Norovirus (common on college campuses and cruise ships)
What are the major characteristics of noroviruses?
+RNA virus with capsid
Resistant to environmental pressures (drying, detergents, acids, temperatures)
Transmitted fecal-oral route
Cause outbreaks of gastroenteritis, generally resolves after 48 hours
What is the pathogenesis of norovirus?
Cause disease by compromising the function of the intestinal brush borders, preventing proper absorption of water and nutrients
Major characteristics of the enterovirus group of viruses include all of the following EXCEPT:
A. Fecal-oral route of transmission
B. Acid stable virion
C. Proteolytic processing of the viral polyprotein to yield capsid and nonstructural proteins
D. Primary viremia leading to spread of the virus to target tissues
E. Majority of infections result in frank cases of disease
E. Majority of infections result in frank cases of disease
What is the most common form of infection associated with enterovirus D68?
Respiratory infection
What are the mechanisms of transmission for enterovirus D68?
Respiratory and contact with contaminated surfaces
What are the current methods of detection for infections with D68 virus?
- PCR
2. Isolate virus and culture for cytopathic effect
What is the pathogenesis of infection with D68?
Viremia leading to respiratory tract infection
Are there antiviral therapeutics for D68 infections?
Pleconaril for several cases
Are there vaccines available to protect against infection by D68?
No vaccines are available
Are there long term consequences to infections with D68?
Long-lived protective immunity
What is the family and genome of Hepatitis A virus?
Single-stranded positive RNA enterovirus
How is HAV most commonly transmitted?
Fecal-oral
What is the recommended current method of detection for hepatitis A infection?
Serology by Ab capture for HAV specific IgM
What is the mechanism of pathogenesis for HAV?
Viremia resulting in targeting of the liver
Are there anti-viral therapies available against HAV?
Vaccine can be administered during the prodrome period of infection
Is there a vaccine available for protection against HAV?
Killed-virus infected vaccine
Are there long-term consequences of an HAV infection?
Long-lived protective immunity
What is the most common manifestation of a rotavirus infection?
Epidemic diarrhea in young children
How is rotavirus most commonly transmitted?
Fecal-oral
What samples should you send to the lab to make a proper diagnosis of rotavirus?
Fecal sample
What is the pathogenesis of rotavirus?
Enterotoxin production causing calcium release
Are there any effective anti-viral agents available against rotavirus?
No
Is there a vaccine currently available for Rotavirus?
Yes - Rotateq (live-attenuated pentavalent vaccine) and Rotarix (live-attenuated vaccine protective against one genotype; more common because fewer doses are required)
Are there any long-term consequences to rotavirus infections?
Short-term immunity with less severe reinfection
What is the most common manifestation of a norovirus infection?
Diarrhea associated with viral infections on cruise ships
How is norovirus most commonly transmitted?
Fecal-oral
What test is the most common to make a Norovirus diagnosis?
RT-PCR by the public health department
What is the pathogenesis of Norovirus?
Lysis and shedding of gut epithelial cells
Are there any effective anti-viral agents available against Norovirus?
No
Is there a vaccine currently available for Noravirus?
No
Are there any long-term consequences to norovirus infections?
Norovirus type-specific immunity
