RNA Viruses Flashcards
What are the common features of RNA viruses?
1) RNA is the genetic material and the template for protein synthesis
2) dual purpose of replication is to copy the genome and make mRNA
How to make RNA from RNA?
unique viral enzyme called RNA dependent RNA polymerase (RDRP)
What does (+) strand RNA mean?
(+) strand is the sense strand = mRNA
**can directly make proteins out of (+) RNA
What does (-) strand RNA mean?
(-) strand is the antisense strand = template for mRNA
**cannot directly make proteins out of (-) strand
Where does RDRP do its job? What’s the exception?
RDRP works in the cytoplasm, but like RNA, nucleoproteins, and accessory proteins are not floating free in the cytoplasm. The exception is influenza virus where the RDRP is NOT in the cytoplasm
Where does genome replication of RNA viruses occur? What’s the exception?
Replication often occurs on cell membranes (endosomes, lysosomes, ER vesicles), which concentrates all the components. Exception is influenza virus.
Comment on the efficiency and fidelity of RDRP and the implications
RDRP is very efficient, but fidelity is very low because no proofreading. This is one of the reasons why RNA viruses have such high mutation rates and make developing vaccines difficult.
T/F: All RNA virus stocks are mixtures of wild type and mutant forms
True
Causes of RNA Virus Genetic Diversity
- RDRP has low fidelity (no proofreading)
- Recombination -exchanging large sections produces new genomes; very likely to occur
- Reassortment -segmented RNA can mix if the cell is infected with multiple strains
Consequences of RNA Virus Genetic Diversity
- mutants arise frequently
- new variants may cause new diseases
- drugs and vaccines lose effectiveness
- viruses are not pure populations
What does quasispecies mean in terms of viruses?
One virus mixture can have a lot of different viruses b/c of the high mutation rate.
Poliovirus (Picornaviridae) is an enterovirus. Describe its genome.
Poliovirus is (+) ssRNA genome, linear mRNA
What does poliovirus infect/is trophic for?
Poliovirus infects GI epithelial cells, may spread to muscles and neurons.
Poliovirus transmission
fecal-oral; persists in water supply; infects only humans
95% of people infected with poliovirus will have asymptomatic acute GI infection, what about the other 5%?
5% will have mild disseminated disease; within the 5%, 1 % will have paralytic infection of motor neurons.
What happens when poliovirus binds to receptors on host cells?
Poliovirus will recognize and bind to receptors. Poliovirus will change shape after binding to receptor. Capsid proteins become hydrophobic and form a pore through membrane. RNA genome enters cells at plasma or endosome membrane.
In the poliovirus RNA genome, the 3Dpol will make
the RDRP
When will poliovirus switch from mRNA transcription to genome RNA synthesis?
When capsid proteins accumulate, new mRNA is packaged instead of translated.
What are some issues with poliovirus genome? What are some ways we fix these issues?
Poliovirus has (+) RNA. Collisions occur btw RDRP and ribosomes on same strand, but they are not a big problem because translation happens first when RDRP is scarce (NEED more RDRP). When RDRP is abundant, no need to make more RDRP so (-) RNA synthesis occurs later.
T/F: All RNA viruses encode RDRP
True
If RDRP is not present in the virion, then
protein synthesis is necessary to make RDRP before replication can begin
T/F: (-) RNA and dsRNA must package RDRP in the virion
True because RDRP is necessary to synthesize mRNA to make proteins.
T/F: (+) RNA viruses must package RDRP in the virion
False because (+) RNA is already mRNA, and can make proteins to make RDRP so RDRP is not necessary.
How to prevent polio?
Vaccine and sanitation
How to treat poliovirus?
control symptoms and give breathing support
State the genome, shape and whether it’s enveloped or not: Rotavirus (Reovirus)
segmented dsRNA, icosahedral, naked
State the genome, shape and whether it’s enveloped or not: Influenza Virus (Orthomyxovirus)
(-) segmented ssRNA, helical, enveloped
State the genome, shape and whether it’s enveloped or not: Retrovirus
(+) ssRNA (2 copies), icosahedral, enveloped
State the genome, shape and whether it’s enveloped or not: poliovirus
(+) ssRNA, icosahedral, naked
Symptoms of Rotavirus Disease
- severe gastroenteritis
- profuse watery diarrhea
- dehydration
- maladsorption
Rotavirus Disease is a seasonal viral infection, peaking in which season
winter
Rotavirus Life Cycle
- enters via endocytosis
- forms an early endosome
- uncoats as it emerges from endosome
- RDRP first transcribes mRNA
- After viral proteins are translated, new virions and genome are synthesized in the cytoplasm
- Virions assemble and then bud into the rough ER
- Egress is via excytosis or by cell lysis
rotavirus virions mature in gut lumen, then can do what 2 things
- infect more enterocytes or 2. shed in profuse diarrhea
How to treat someone with Rotavirus disease?
Oral rehydration solutions
How to prevent Rotavirus?
Live-attenuated vaccines (Rotarix and Rotateq)
List symptoms of uncomplicated influenza virus disease
- upper and/or lower respiratory tract involvement
- fever, headache, myalgia and weakness
List symptoms of complicated influenza virus disease
- primary pneumonia
- secondary bacterial pneumonia
- mixed viral and bacterial pneumonia
- muscle involvement: myositis (pain) and rhabdomyelitis (breakdown)
Influenza virus has a segmented, (-) ssRNA. Normally RDRP works on RNA viruses in the cytoplasm, but in the case of influenza virus, what happens?
Genome segments traffic to the nucleus for transcription and replication by RDRP
Where do influenza viral proteins and genome segments accumulate before virion assembly?
Viral proteins and genome segments accumulate at the plasma membrane, then assemble into virions, and egress via budding
What is the significance of Neuramindase (N antigen)?
Neuramindase releases virions from sialic acid on cell surface. Without it, the virions cannot be released.
Flu can be treated with anti-viral drugs and prevented with vaccines. Most vaccines are trivalent containing…
2 A strains and 1 B strain -the most prevalent ones
Why does one have to get different flu vaccines each year?
the influenza virus undergoes reassortment and mutation leading to different subtypes. Hence, flu vaccines have to contain different strains each year to protect against the ever-changing virus.
What are the 7 stages of HIV Disease
- Exposure to virus (transmission)
- Primary HIV infection (acute phase)
- Seroconversion
- Latent period
- Early symptomatic HIV infection
- AIDS (CD4 cell count below 200/mm^3)
- Advanced HIV infection (CD4 cell count below 50/mm^3)
HIV Cell Tropism
- only humans can be infected
- virus binds to CD4 and chemokine receptors on T cells and macrophages
- **depletion of these cells and chronic immune activation cause immunodeficiency
In HIV life cycle, what happens after the virion fuses with the plasma membrane?
The reverse transcriptase enzyme converts the (+)ssRNA genomes into dsDNA
T/F: In HIV infection, the dsDNA genomes integrate into the host chromosome for life.
True
Which polymerase transcribes mRNA from integrated genome of HIV?
host RNA polymerase II transcribes mRNA from the integrated genome
In HIV life cycle, viral proteins and how many genomes bud from the plasma membrane?
2 genomes
Where does virion maturation occur in HIV life cycle?
Virion maturation occurs outside the cell when the viral protease cleaves the capsid proteins, forming the final trapezoidal shape.
How to diagnose HIV?
- serologic assays for antibodies
- nucleic acid assays for viral load
- CD4 T cell count
HIV treatment
- anti-retroviral therapy
- drugs must be combined to avoid resistance
- new formulations reduce pills and doses, increase compliance
There are many HIV drugs. What are the goals of HIV treatment?
- durable suppression of HIV viral load
- restoration of immune function
- prevention of HIV transmission
- prevention of drug resistance
- improvement in quality of life
Poliovirus uncoats, and their genome (+sRNA) undergoes
translation to make RDRP
There are 8 segments of (-)ssRNA in influenza virus that will be released in cytoplasm and have nuclear localization signals to get to the nucleus. T/F: each segment has its own RDRP.
True
What happens when influenza virus loses neuramindase? Which 2 anti-viral drugs are used to treat against the flu and use this knowledge?
The viruses will be stuck on host cell’s surface b/c neuramindase is used to cut the sialic acids. Zanamivir (Relenza) and Oseltamivir (Tamiflu) are sialic acid analogs that inhibit neuramindase so virions remain attached to cells.
