MCB5505 Exam 2
Ebola is a more recent problem in Africa. T/F
False, scientists think it has been a problem for a long time, but western colonization brought a lot people together that were living near isolation
The healthier the immune system, the less damage Ebola causes it to create. T/F
False, the healthier, the more damage caused
Recurrent episodes of HSV are more sever than the primary infection. T/F
False, they are less severe
Shingles rash episodes only occur once. T/F
False, they can occur multiple times
Only a few ebola outbreaks can be traced to zoonotic origin. T/F
False, ultimately all outbreaks can
After being infected with Measles, you do not have a lifelong immunity against it. T/F
False, you have lifelong immunity
What family is Ebola in?
Filoviridae
What are the two latent viruses examples talked about?
HSV- Herpes simplex 1 EBV- Epstein Barr
Which HSV is mainly above the waist?
HSV-1
Which HSV is mainly below the waist?
HSV-2
What virus forms a pregenomic RNA and what is the pregenomic RNA used for?
Hepatitis B; used for generating the gapped dsDNA genome
What cells does Hep B infect?
Hepatocytes
Which viruses have a large number of envelope proteins and package numerous tegument proteins?
Herpes viruses
Which two viruses discussed use rolling circle replication?
Herpesvirus and HPV
Describe the course of a latent infection?
High virus levels during the initial infection followed by low or undetectable levels of virus with occasional periods of reactivation when virus levels mimic the initial acute infection
What is the human Parvo virus and what disease does it cause?
Human B19, Fifth disease
Does the rotavirus vaccine protect against a lot of strains?
No, b/c the virus undergoes reassortment, so severity of illness is reduced instead of immunity
Is there N protein present when VSV enters the cell?
No, except for what is on the genome
Which protein is responsible for controlling the switch between making mRNAs and making genome for influenza virus?
Np protein
ss(-)RNA viruses can have single or segmented genomes. T/F
True
Hepatitis B packages a reverse transcriptase inside the viral core. T/F
True, only DNA virus that does
All mRNAs of rotavirus are capped and complete genome copies. T/F
True, they can get copied again and a (-) strand can be made to form new viral genome to package
Which influenza type is the most common, most severe, and most frequently mutates?
Type A
Which influenza type is less common and has only a few H/N glycoproteins on its surface?
Type B
Which influenza type infects both humans and pigs and doesn't have H/N glycoproteins?
Type C
Which influenza type is less common, causes a mild disease in children and least likely to mutate?
Type C
What are the three types of influenza? How do their genomes differ?
Types A-8 RNA segments, B-8 segments and C-7 segments
How is influenza treated?
Usually only for high risk groups or severe illness: -neuraminidase inhibitors to stop virus from breaking out of host cell -M2 proton channel inhibitors that prevent virus replication
What is important for reactivation of HSV and why is it important?
VP16 and HCF-1 cofactor accumulation in the nucleus; supports immediate early gene expression leading to productive reactivation
What HSV proteins are used for open chromatin structure and how does it affect gene expression?
VP16 and ICP0 facilitates acetylation of chromatin which opens it and leads to increased gene expression
Stress stimulates production of what viral proteins to activate transcription for herpesvirus and EBV?
VP16 for herpesviruses and Zta for EBV
What does herpesvirus VP16 do after the genome enters the host cell nucleus?
VP16 interacts w/host transcription proteins to simulate transcription of immediate early genes by host RNA pol
What proteins cover Ebola genome?
VP30 and N
What is one function of Ebola VP35 protein on the immune response?
VP35 inhibits the immune responses that recognize viral sequences and inhibits the initiate responses to fight against viral pathogens
Which Ebola proteins inhibit production of interferon and interferon signaling?
VP40 and VP24
Which viruses make mRNAs that are not complete copies of the genomic viral RNA (vRNA) and both use specific proteins to switch between making mRNA and (+) RNA to serve as a template for genome replication?
VSV and influenza
What is one way translation of VZV differs from the translation of Poliovirus?
VZV translates each protein sequence individually while Poliovirus translates one long polyprotein that is ultimately cleaved viral proteases
What type of spread does VZV use and what impact does it make?
VZV uses cell to cell spread which leads to such a slow incubation
What are the two important tegument proteins involved in the early stages of herpes virus replication?
Vp16 and vhs proteins
How does VZV aerosolize?
When the virus makes it to the superficial epidermis, this is the one place that the virus is released from the cells to get aerosolized
Does Ebola package its own RdRp?
Yes
Is there a vaccine for HBV?
Yes
Does rotavirus package its own RdRp? If so, why?
Yes, it lies just beneath the turrets on the shell b/c it cannot use its (+)strand as mRNA, so it has to be made
Is there a vaccine for rotavirus?
Yes, oral live, attenuated virus vaccine
Which viral protein determines the latent/lytic switch for EBV infected B cells?
Zta
How can an mRNA encode for more than one protein?
a frameshift in coding sequence or splicing event
What is needed to make a copy of a RNA viral genome for inclusion in new viral particles?
a full length genome
What is deadly about parvovirus infection in animals?
dehydration
What is the deadly part of rotavirus illness?
dehydration
What cells does Ebolavirus infect that disrupts the immune response and normal cellular processes?
dendritic cells, macrophages and monocytes
Which characteristic of Measles infection is linked to development of immune amnesia?
destruction of memory immune cells
What are the symptoms of rotavirus?
diarrhea, fever, vomiting
During rolling circle replication, cellular enzymes will repeatedly sit down on the newly synthesized strand of DNA to make the second strand of the dsDNA genome. This process is termed?
discontinuous DNA synthesis
What animals are affected by Parvovirus?
dogs and cats
What is the mode of transmission of influenza?
droplets from coughing/sneezing
What type of genome do most reoviridae viruses have?
dsRNA
How does Zta affect chromatin structure and lead to reactivation of EBV?
during latency, chromatin is heavily methylated until Zta is produced and structure allows it to bind preferentially to methylated repressed promotor regions and reverse the effect by bringing in histone tags that activate expression of early genes
What is unique for ssDNA virus packaging?
either a (-) strand or a (+) can end up in the final new viral particles as the genome isn't polarity dependent
What happens one to two days into prodromal phase of Measles?
enanthem- rash on mucus membrane, Koplik spots
What happens after prodromal phase of rabies?
encephalitis: -fever, agitation, hydrophobia, pharyngeal spasm, coma, flaccid paralysis, seizures and respiratory/vascular collapse
How does VSV enter the cell?
endocytosis
What does the rotavirus produce that causes the illness?
enterotoxin
IS Herpesvirus enveloped or non-enveloped?
enveloped
Is Ebola enveloped or non-enveloped?
enveloped
Is Hep B enveloped or non-enveloped?
enveloped
Is VSV enveloped or not enveloped?
enveloped
Is influenza enveloped or non-enveloped?
enveloped
Is measles enveloped or non-enveloped?
enveloped
Which is the FIRST cell type infected by EBV?
epithelial cells
What cells does EBV infect?
epithelial cells and B cells
What phase comes after Measles prodromal and what are the symptoms? How long does it last?
exanthem phase-red, patchy maculopapular rash starting at head and spreads to extremities -fades after 4 days
What is parvovirus called in cats?
feline leukemia
What are the symptoms of Fifths disease?
fever and headache, rash after fever breaks
What are the symptoms of chickenpox?
fever, flu-like, skin rash
What are the symptoms of influenza?
fever, headache, runny nose, sore throat and cough
What are some early infection symptoms of Ebola?
fever, headache, stomach pain, vomiting and diarrhea
What are the symptoms of Hep B?
fever, malaise, nausea, hepatomegaly (abnormally large liver), pain
What are the symptoms of an EBV illness?
fever, pharyngitis, lymphadenopathy, fatigue (exaggerated), atypical lymphocytosis and splenomegaly
What other areas can HSV affect?
finger tip/nail bed, trunk, extremities and head, eye and in rare cases the CNS
How many mRNA segments does VSV have?
five
What symptoms are in the prodromal phase of rabies?
flu-like, nausea
What is unique about Hep B replication vs other DNA viruses and why?
for most other DNA viruses, DNA genome is copied in the nucleus b/c that is where cellular machinery is located; Hep B brings own enzyme to do that work so it is not confined to the nucleus
How long is influenza contagious?
from a day before symptoms present and up to a week or two after
After HSV passes though epidermis, what does it do?
fusion with sensory neuron and the nucleocapsid gets transported through axon to neuron cell nuclei
What does the poxvirus extracellular particle do?
goes on to infect other cells
Inverted terminal repeats form which important structures of linear ssDNA molecules?
hairpin structures
What does type C influenza use to enter and exit host cell?
has hemagglutinin esterase fusion protein
What type of symmetry does VSV have?
helical
What protein does Measles use to bind to receptor?
hemagglutinin
What enzymes does influenza use to bind and cleave cellular sialic acid, respectively?
hemaglutinin and neuraminidase
What are some peak infection symptoms of Ebola?
hemorrhage, convulsions, rash, severe diarrhea, confusion, chest pain, cough and coma
What is the most commonly used receptor by AAV?
heparan sulfate
Which receptor does herpesvirus use?
heparin sulfate or chondroitin sulfate
What receptor does Hep B use?
heprin sulfate
What family does HSV belong to?
herpesviridae
Is it viral polymerases or host cellular polymerases that generate mRNAs for Hep B?
host cellular pol
Why does VZV spread the way that it does?
its glycoproteins cause an infected cell to fuse w/ a neighboring infected cell where it inserts its viral DNA. If it were to spread in a more common way, it would overwhelm the host immune system and kill the host--this way it give the immune system time to overcome
What are latency associated transcripts (LATs)?
only viral transcript that is made when all other genes are silenced
What viral family is influenza in?
orthonyxoviridae
How does influenza genome released?
pH lowers in endosome, viral envelope fuses w/ endosomal membrane
Explain Hep B's genome
partially ds, always circular with small pieces of RNA bound to one end and packaged polymerase bound to the other end
If a patient has transitioned into HBV chronic phase, but they appear to be healthy. Could they still be infected? If so, what would you find?
patient likely to have presence of surface Ag and/or core Ab without DNA or "E" Ag meaning that there is virus present, but it is not replicating; can still be contagious
What is the final symptom of Measles?
persistent cough
What are the more serious complications with chickenpox?
pneumonia, meningitis, encephalitis, vasculitis (stroke), embryo death if pregnant
What is the method of diagnosis for rabies virus?
post mordem examination
What two types of RNA is made by Hep B and what are they used for?
pregenomic RNA-template for (-)DNA strand mRNAs- viral proteins
What is viremia?
presence of viruses in the blood
What is the purpose of VSV N protein strand coating?
prevents the RdRp from stopping at the intergenic sequences
What are herpesvirus late proteins?
primarily structural proteins and others are for viral assembly and egress
What are viral early genes?
proteins that are encoded to induce cell division that are expressed first during viral transcription/translation
What symptom(s) of Measles is/are a result of immune response?
rash and Koplik spots
What phase follows exanthem phase of Measles and how long does it last?
recovery- 10 to 14 days
What is the function of immediate early genes?
regulating expression of immediate early genes and also active the transcription of next set of early genes
Where does rabies virus replicate and spread?
replicated in muscle tissue and gets into sensory/motor nerves and travels via retrograde axonal transport to spinal cord; from spinal cord, virus jumps across synapses into next neurons and travels up to brain
How is VZV transmitted?
respiratory droplets from skin lesions
What are the first cells infected by VZV?
respiratory epithelial cells
What ribosomes make the envelope proteins for VSV?
ribosomes bound to the ER
What ganglia is present in the genitals that HSV infects?
sacral ganglia
What type of ss(-)RNA genome does influenza have?
segmented
What does latent infection require?
selective control of viral gene expression
What illness is rotavirus the #1 cause of?
severe childhood diarrhea
How is HBV transmitted?
sexually, or child birth
What molecule on the host cell does influenza virus bind to?
sialic acid
How is reactivation of EBV accomplished?
signal is not well understood, however, signal transduction cascades result in Zta production
What type of ss(-)RNA genome does VSV have?
single, unimolecular
What type of cells are generally undergoing active replication?
skin, mucosal epithelium in respiratory sys or gut
What the symptoms of HSV?
skin/mucous membrane lesions
What happens to some late proteins?
some are translated by free ribosomes, while proteins for surface glycoproteins are made by ER ribosomes
What happens to the herpesvirus tegument proteins after virus enters the host cell?
some are transported with nucleocapsid to the nucleus while some remain in the cytoplasm
What are viral factories and what do they contain?
specialized sites w/in the host cell where new viruses are assembled and they contain cellular membranes most likely taken from the ER
What type of genome does Measles have?
ss(-)RNA
What needs to happen before Measles genome is ready for translation?
ss(-)RNA genome needs to be transcribed by RdRp into (+)RNA strand
What kind of genome does Ebola have?
ss(-)RNA, unimolecular
What types of viruses are some of the smallest known?
ssDNA viruses
When and how long are people contagious when infected with Measles?
starting from final day of incubation period through prodromal and exanthem phase -4 days before and 4 days after onset of rash
DNA genomes of Hepatitis B are formed using a method called what?
strand exchange
What are some reactivation triggers?
sunburn, stress, nerve damage, steroids, heavy metals, trauma
What is VHS?
suppresses host gene expression for herpesvirus
What proteins play a crucial role in replication and are located beneath the envelope, but outside the capsid of herpesvirus?
tegument proteins
What is responsible for Measles prevalence in lymphocytes?
that the virus binds to CD150 on immune cells and APCs
What type of RNA gets made next inside the new rotavirus core?
the (-) strand for the full genome
Under some circumstances, poxviruses can be released from the cell before acquiring an envelope membrane from what?
the Golgi
How do rotavirus mRNAs get translated?
the RdRp and mRNAs exit the viral core to the cytoplasm through portals located at the turrets that are opened during the encoding process
What helps provide the symmetry of VSV?
the binding of N protein with both the viral RNA and capsid proteins
Where does the AAV polymerase bind for copying DNA template?
the end of terminal repeat in rep ORF
What impacts the cellular tropism of AAV?
the fact that it can bind to a lot of different receptors
What is unique to influenza replication?
the genome migrates to the nucleus and is small enough to enter through the nuclear pore
What needs to happen first before ssDNA genomes are transcribed?
the genomes must be repaired
What happens to AAV structural mRNAs and the proteins they encode for?
the mRNA leaves the nucleus and gets translated in the cytoplasm, then the structural proteins travel back to the nucleus for assembly
What happens to rotavirus as it moves through the endocytic pathway?
the middle shell of sub viral particle gets digested away and is left with just the core
How does the new rotavirus particle complete?
the new core particle with full, complete genome merges with other viral proteins made in cytoplasm and exits the cell
What happens after herpesvirus enters the cell?
the nucleocapsid docks @ nuclear pore and releases DNA into nucleus where is quickly becomes circularized
How does VSV polymerase make separate mRNA sequences?
the polymerase comes to a special intergenic sequence which causes it to stop making mRNA. the polymerase then crosses over the sequence and recognizes starting sequence to make mRNA again until it comes to another intergenic sequence
How does rotavirus undergo reassortment?
the segmented genome allows for mutations and if two different strains are in the same cell, a new viral strain can be easily made
How is the latency of EBV accomplished?
the transcription of Zta is blocked by cellular repressors
What part of dsDNA viral genome replication can be used as a target for antiviral therapy?
the viral enzyme that cuts the newly replicated genome for packaging
Where do the mature poxviruses go?
the virus goes to Golgi to acquire a second double membrane to form intracellular wrapped particles
Why are the shells of rotavirus important?
the virus stays with the endosome until it fuses with lysosome, so it encounters extremely low pH
Why are there immune privileged areas?
they are areas of sensitive tissues that would otherwise be subject to extreme damage if inflammation should occur due to immune response
What are major LATs?
they are precursors for production of miRNAs
What do the terminal repeats on AAV genome do?
they cause the genome to form hairpin-like structure @ both 5' and 3' ends
Why are they the smallest viruses known?
they do not encode many viral proteins
What makes poxviruses unique?
they don't have access to cellular machinery for making mRNA/copying DNA since they replicate in the cytoplasm, so they have to package their own enzymes which is why they are so large
What happens to the newly packaged poxvirus at viral factories?
they get released and mature into classic brick-shaped intracellular mature viruses upon proteolysis and released from these viral factories
What is unique about the reovirus structure?
they have two concentric shells surrounding the core/substructure
What happens to the VSV proteins that are not involved with replication?
they migrate to the cell surface where the envelope proteins embedded
What happens to the wrapped poxvirus particles and how do they get there?
they move to the cell surface on microtubules and fuse w/ plasma membrane for form cell associated particles
Where do the VSV envelope proteins go and how do they get there?
they travel through the host cell secretory pathway, pass thru the Golgi and to the cell surface to embed into the membrane
How are ssDNA genomes made?
through strand displacement
How do Herpes and pox viruses infections occur?
through the regulated expression of their viral genes
What symptom signals HSV prodromal phase and how long before blisters appear?
tingling sensation, 1-2 days before
What is thought to be the function of miRNAs and what is the example for this theory?
to block lytic gene expression during latency; second X chromosome in females is coated in miRNAs to shut it down
What is VP16?
transcriptional activator for herpesvirus
Where do herpesvirus immediate early proteins go and why?
transported back to the nucleus for further regulation of transcription and larger take over of cellular machinery
Which ganglion of the peripheral nervous system is a common site for HSV-1 latent infection?
trigeminal ganglion
How does Ebola get into a host cell?
unknown receptor, unknown specific entry, but know endocytic pathway. Virus fuses with endosomal membrane by binding NPC1 protein to release genome
What is the mech of entry for Hep B?
unknown, but think caveolin mediated endocytosis
How do ssDNA genomes replicate? (what mechanism)
using a strand displacement mechanism
What preventative measure is the most effective for influenza?
vaccination--inactivated or live attenuated, both trivalent which is a mixture of 3 stains predicted to be prevalent
How is HBV contracted?
via blood contact
How is the VSV viral genome released into the cell?
viral membrane fuses with endocytic vesicle
Regulation of herpes and pox virus infections are performed by what?
viral proteins
What does the transcription of poxvirus intermediate genes require?
viral proteins hat are products of early genes and a cellular protein which gets recruited from the nucleus to the cytoplasm
What are poxvirus late genes translated to make?
viral structural proteins, enzymes and other essential proteins that will get packaged b/c they are needed early in the next round of infection
Where does the hemorrhagic nature of Ebola come from?
virus manipulates macrophages into activating neutrophils which signal blood vessels to release more fluid
What is the first immune system disruption by Ebola?
virus prevents dendritic cells from activating specialized antiviral forces and manipulates it into sending signal proteins to trick specialized cells into ending own lives prematurely
How is HSV diagnosed?
visual appearance of lesions, and conformational tools like PCR or viral culture
How does HSV get past the epidermis?
when HSV replicates some gets released through the basal layer
What is atypical lymphocytosis?
when lymphocytes get infected by EBV, the nucleus gets larger like reactive cytotoxic T cells
How do neighboring cells get infected with poxvirus?
when the wrapped virus particle leaves via exocytosis it attaches to neighboring cell to start process over again
What happens when the concentration of VSV N protein rises in the cell?
when there is enough available, it begins coating the newly made (+)RNA strand so the full length (-) strand can me made
When is HSV most contagious?
when virus-filled lesions are present
How does Measles spread throughout the body?
within a few days after infection of respiratory epithelial cells, virus spreads through local tissues and gets picked up by dendritic cells and alveolar macrophages that carry the virus from local tissues in lungs to lymph nodes. From there, the virus gets into blood stream and spreads further to intestines and brain
Where is HSV subject to immune infection after epidermis?
within the sensory neuron cell body/ganglion cluster
Where does all the genome replication take place reoviruses?
within the viral core
When and where does Pox virus mRNA get synthesized?
within the viral particle prior to uncoating
Where does RNA synthesis by dsRNA viruses occur?
within viral core
How long does rotavirus last?
~1 week
How often does HBV become chronic and what is a contributing factor?
~20% of cases, age--<6y/o goes up to ~50%
What percentage of US adults are infected with EBV?
~95%
How long is the prodromal phase of Measles and what are the symptoms?
-3 days -high fever -cough -conjunctivitis -coryza
How are the influenza mRNAs shorter than the (-) segment?
-5' end of mRNA has an extra sequence that is derived from the host cell; if copied, any newly made virus wouldn't replicate properly -3' end falls ~20nt short; short enough that the virus no longer makes a full length copy so these mRNAs can't be used to make a full length copy
What receptor(s) is/are used by Measles?
-CD46 on all nucleated cells -CD150 on signaling lymphocytes activation molecule (SLAM) found on immune cells and APCs -Nectin 4 cellular adhesion molecule
What are the 3 major HBV antigens?
-HBV surface Ag -Core Ag -"E" Ag secreted by infected cells and/or viral DNA
What is necessary for establishment of latency in HSV?
-LATs -miRNA
Describe the steps of strand displacement
-cellular pol repairs the viral genome binding to ORF and moves along genome flattening hairpin and making second strand -ds molecule serves as template for transcription and formation of Rep 78/68 -Rep 78/68 nicks viral genome @ other end of terminal repeat -DNApol comes and makes copy of hairpin sequence; now have two hybrid strands -DNApol begins making copy of genome displacing one of the original strands; two hairpins form and origin of rep can be bound by host DNApols -when DNApol comes to end of genome and falls off, left with DNA genome that is part old and new, plus one ds genome to serve as template for making mRNA or nicked by Rep 78/68
Who are considered high risk of influenza?
-children <6mo: Reye syndrome -pregnant women -adults >65y/o -chronic heart or lung disease
What are some signs of viral hepatitis?
-incr levels of transaminases in the blood -atypical lymphocytes -jaundice
Why was the Spanish flu so bad?
-killed more healthy people than immunocompromised -possibly produced cytokine storm, a systemic inflammation that's often fatal -WWI aided in death toll/spread -increased global travel
What are some side effects of the rotavirus vaccine, new and old?
-new: GI symptoms as elicits immunity -old vaccine caused intussusception which is where a part of the bowel telescopes causing intestinal obstruction
How is it so easy for antigenic shift to occur with influenza?
-other types of influenzas replicate in the same manner as human -if two different influenza viruses infect the same cell, it is easy for the migrating pieces of mRNA to get mixed/shuffled around
What are some complications of Measles?
-pneumonia -diarrhea -encephalitis -bacterial super infections from suppressed immune system -SSPE in children <2y/o
What are some similarities between pox virus and herpes virus infection cycles?
-proteins that are involved in the early steps of viral replication are packaged within the viral particle -late genes encode proteins for viral structural components
What ways is influenza diagnosed?
-rapid test (ELISA on a stick) -viral culture -PCR
How is rabies transmitted?
Animal bite
What cells does EBV establish latent infection?
B lymphocytes
Why is Measles so contagious?
B/c it can spread through air; can live up to 2hrs in air particles or surfaces
How does herpesvirus exit the host cell?
Capsid proteins migrate to the nucleus for assembly with DNA along with some of the tegument proteins that are in nucleus. Viral particle buds from inner nuclear membrane into perinuclear membrane acquiring a temporary envelope. It gathers more tegument proteins as moves through perinuclear until particle fuses with other nuclear membrane gets released into vesicle in cytoplasm that transport virus to plasma membrane for release by exocytosis
What are some immune privileged sites?
Central and peripheral nervous systems -brain, eyes, spinal cord, testicles and pregnant uterus
Describe what happens with Jaundice?
Conjugated bilirubin leaks out of bile ducts when hepatocytes are destroyed/die, also end up with unconjugated bilirubin as hepatocytes lose ability to conjugate it and make it H2O soluble. Some of conj bilirubin gets filtered into urine darkening the color. Urobilinogen gets produced b/c bilirubin is reduced in the gut, redirected to kidneys and excreted
What are the first cells Ebola attacks and how does it enter/attack?
Dendritic cells, binds receptor for cell transport. Attacks by disabling cells protective mech and reprogramming it to replicate virus
Unlike ss(-)RNA viruses, the mRNA of Reoviruses are full length copies of the viral genome. T/F
False
ssDNA viruses only package a (+) strand of DNA into new viral particles. T/F
False
Influenza can cause immune amnesia. T/F
False, Measles
Not all of the influenza genome segments encodes for an mRNA. T/F
False, each segment encodes for at least one mRNA
Monkeys are dead-end hosts for Ebolavirus. T/F
False, humans are
dsDNA viruses have circular genomes inside the viral particle. T/F
False, inside of the viral particle it is in linear form
The entire herpesvirus genome is replicated at one time. T/F
False, it has timing mechanisms that control when certain genes are expressed
Varicella Zoster Virus is human herpesvirus 5. T/F
False, it is herpesvirus 3
EBV is human herpesvirus 3. T/F
False, it is human herpesvirus 4
All neurons in a ganglia are latently infected. T/F
False, not all
Hep B makes RNAs and copies DNA inside host nucleus. T/F
False, only RNA is made in nucleus
Shingles is an example of which type of infection?
Reactivated latent infection
What can occur in response to several physical or emotional stresses?
Reactivation of latent infection
Which viruses have a unique structure compared to other viruses?
Reoviruses
What is the first protein made for AAV?
Rep 78/68
What family does rabies belong to?
Rhabdoviridae
What is the most famous virus in reoviridae family?
Rotavirus
Which virus has unique characteristics that distinguish it from other enteric viral infections?
Rotavirus
One day you find yourself sick with both diarrhea and vomiting. Since you've taken Virology, you know that you are likely infected with either Norovirus or Rotavirus. Which aspect of your illness or symptoms would give a good indication of which virus you were infected with?
Rotavirus is a pediatric disease, so I most likely have a Norovirus infection
How is Measles diagnosed?
Serology demonstrates IgG or IgM against the measles virus
What is the recurrent infection of VZV?
Shingles/Zoster
Explain persistent infection of EBV?
Some EBV escape the immune system during primary infection which go on to latently infect resting memory B cells. These memory B cells only express LMP-2 on surface which doesn't signal immune response. Some of these cells reactivate and express LMP-1 and get attacked by cytotoxic T cells or can become reactivated when in close contact w/ epithelial cells of tonsils which re-enter lytic phase
What are needed to establish and maintain latency?
Specific viral genes
What does Ebola do to your immune system mechanisms?
it turns them against you
Which HBV Ag is the marker for an active infection?
"E" Ag
What are the functions of poxvirus early genes?
-some early proteins have sequence similarity cellular growth factors and can induce proliferation of neighboring host cells--these get secreted and help viral egress and infection of new cells -others counter act the host immune defense mechs and induce the uncoating of viral capsid which releases viral genome -mediate replication of genome w/in cytoplasm
What are some other symptoms of Shingles?
-superimposed bacterial skin infection due to scratching -opthamalic involvement (cornea and retina) -Hutchinson sign (nose vesicles) -Ramsay Hunt Syndrome (ear canal) -paralysis
What is present at onset of HBV infection phase?
-surface Ag -viral DNA -"E" Ag -IgM Ab against core
What are important features of ssDNA replication?
-the use of host cellular enzymes in DNA replication -the function of the Rep 78/68 protein
When do symptoms appear after infection with influenza?
1 to 4 days
How long is rabies virus incubation?
1 week to 1 year depending on bite site
What are the two characteristics of latent infections?
1) lack of efficient expression of many viral genes 2) activation of a latent phase transcriptional program
The P protein (reverse transcriptase) of Hepatitis B has three distinct functions. What are they?
1) priming 2) reverse transcribing 3) DNA synth
What are the 3 functions of Hep B viral polymerase?
1) priming 2) reverse transcription 3) DNA synthesis
What are the 3 different patterns of HSV illness in neonates?
1) skin/eye mucous membrane infection 2) CNS infection 3) disseminated infection
How long is the Measles incubation period?
10 to 14 days
What type of genome does poxvirus have?
2 DNA strands that are covalently connected at the ends by terminal unimpaired loops
How many open reading frames does AAV have and what purpose do they serve?
2 ORFs- rep ORF involved in replication, and cap ORF involved in capsid production
How long is the incubation period for rotavirus?
2 days
How long is the incubation period for VZV?
2 weeks
How long is Ebola's incubation?
2-21 days
How long does a Shingles rash episode last?
3 to 5 days
How many origins of replication does herpesvirus have and why?
3, allows large viral genome to replicate efficiently
How long is the infectious process of EBV?
4-8 weeks
How many proteins do each of influenza's mRNAs encode for?
5 of 8 encode for 1 protein, and the other 3 encode for two to three proteins
How long does the chickenpox rash typically last?
5-7 days
How many mRNAs does Ebola encode for?
7
How many segments is influenza genome divided into?
8 segments
Describe Measles replication cycle to exiting the cell
After membrane fusion, genome is released into the cytoplasm and mRNAs are made. Non-structural proteins are made by free ribosomes and structural proteins are made by ribosome of ER and sent to cell membrane to be embedded. (+)RNA strand is made for replication of genome; when coated in N protein, the strand and matrix proteins are trafficked to cell surface to interact with glycoproteins. New particle buds off
Is Measles eradicated?
No, antivax movement causes small # of infections
Explain primary infection of EBV?
EBV infects through the tonsils where a lot of resting B cells are found. Infected B cells express both LMP-1 and LMP-2 on surface which leads death by cytotoxic T cells and/or NK cells
What happens to the EBV infected cell if Zta is NOT present?
EBV remains latent
Where are Hep B viral surface proteins made?
ER
What happens to the host ER when poxvirus infects?
ER gets taken over by the virus and gets reorganized by viral proteins to form characteristic crescent shape seen during poxvirus infection
What happens with dsRNA viruses prior to viral release into the cytoplasm?
Endosomes containing dsRNA viruses fuse with the lysosome
How does Measles enter host cell?
F protein fuses with membrane after H protein binds to receptor
All herpes virus tegument proteins remain in the cytoplasm after uncoating of the virus. T/F
False
During chickenpox infection, skin lesions result from the primary viremia. T/F
False
Ebola can be spread though food and water. T/F
False
The coordinated regulation of herpes virus infection is controlled by host proteins in response to the production of VP16. T/F
False
The rotavirus genome gets released into the cytoplasm prior to the generation of mRNA. T/F
False
Describe Hep B particle assembly to exiting host
In the cytoplasm, capsid protein and P-protein (RT) join w/ pregenomic RNA. Pol binds to end of pregenomic RNA and capsid forms around complex and migrates to ER to join w/ envelope proteins by budding into ER. Then virus comes out of ER in multi-vesicular body to fuse with outer membrane for release
How do LATs alter chromatin structure?
LATs facilitate methylation of chromatin which decreases gene expression
What is immune amnesia?
Measles virus uses SLAM receptor on memory B and T cells to infect them. These cells are targeted for destruction. This causes a loss of immune memory for whatever the memory cells were generated against. However, they are replaced with memory cells for Measles--strong immunity.
What protein is essential for making a full length (+) RNA strand of VSV?
N protein
What other immune cells does Ebola attack?
NK cells, guard cells, macrophages and monocytes
What protein does influenza use when replicating genome that is similar to a VSV N protein? What purpose does it serve?
NP protein -control switch between making mRNAs and full length genome
How does influenza prevent the (+)RNA strand from being truncated?
NP proteins bind to newly formed (+)RNA so polymerase doesn't pull on the host sequence @ 5' end as well as preventing truncation @ 3' end
What protein does Ebola bind to release genome into host cell?
NPC1 protein
Describe the process of influenza genome replication
Once genome enters nucleus, segments are converted into mRNAs b/c has own RdRp. mRNAs then leave the nucleus to get translated. Eventually full length (+)RNA and subsequent (-)RNA also made in nucleus. (-)RNA is transported out of the nucleus and gets incorporated into new particles; envelope proteins transcribed by ribosomes on ER, enter secretory pathway to cell membrane and other proteins made by free ribosomes migrate to cell surface to get packaged
How is HBV diagnosed?
PCR for HBV Ag
What family does Measles belong to?
Paramyxoviridae
What was the family of ssDNA viruses discussed?
Parvoviridae
Which virus causes severe infections in animals and less severe infections in humans?
Parvovirus
Explain how Hep B genome is made.
Pol bound to 5' end of pregenomic RNA, with terminal protein attached, initiates strand exchange and RNA pol moves with it and eventually makes complete copy of (-) strand. The RNA template is removed as DNA synth proceeds. A portion of RNA primer remains bound to (-)DNA strand to serve as primer for (+)DNA strand. RNA piece jumps to complementary seq for second template exchange. It gets picked up by RT and begins synth of a new (+)DNA. After, pol jumps back to end of (-)strand circulating partial dsDNA. The synth remains incomplete and packaged with full length copy of (-) DNA and partial copy of (+) strand
What is the largest virus talked about so far?
Poxvirus
What enzyme comes packaged in the influenza virus capsid, attached to the (-)RNA segments?
RNA polymerase
Which activity of the polymerase is responsible for degrading the pre-genomic RNA during Hep B DNA replication?
RNase H activity
What is caused by several viruses within the same family and is 100% fatal if not treated before symptoms begin?
Rabies
What influences ssDNA virus replication mechanisms?
The small size of the virus and their genomes
During pox virus assembly, viral factories are formed within the cell. T/F
True
During translation some viruses make a single mRNA transcript from the genome, while other viruses make individual mRNAs. T/F
True
Ebola encodes proteins that block the immune response. T/F
True
Host polyermases are responsible for generating ALL of Hep B RNAs. T/F
True
In Hep B replication, cellular enzymes are responsible for generating mRNA. T/F
True
In general, HSV 2 tends to infect and cause symptoms below the waist. T/F
True
Measles has killed more people in Africa than the last outbreak of Ebola. T/F
True
Pox and herpes viruses both express genes that modulate the host as well as the virus. T/F
True
Pregenomic RNA is used to generate new viral genomes. T/F
True
Regulation of early and late genes occur at the transcription level. T/F
True
The primary infection of oral herpes often results in disease symptoms that are MORE severe than the symptoms of recurrent infections. T/F
True
What is splenomegaly?
abnormal enlargement of the spleen due to the increased amount of B cells and cytotoxic cells that are after them
What are some complications of influenza?
acute otitis media, bronchiolitis, croup, sinusitis and pneumonia
What does the timeline of a latent infection look like?
acute symptomatic zones followed by areas of quiescence then re-enters acute symptomatic zones repeatedly
What is the most notable ssDNA virus in Parvo family?
adenovirus associated virus (AAV)--gets help from adenovirus
When should a person with an animal bite get a rabies vaccine?
after animal bite and before symptoms show up
When does the production of poxvirus early mRNAs begin and why?
after entry and is occurring even before viral genome is released into the cytoplasm b/c the virus packages RNA pol
What is the infection path of VZV starting from inhalation to skin?
after inhalation, virus infects respiratory epithelial cells and spreads to the tonsils. From there, it infects T cells that circulate in the blood until makes it to the skin
When is Hep B considered chronic?
after virus persists for more than 6 months
What does the particular receptor binding allow herpesvirus to do?
allows the virus to travel along the external membrane of the cell until it binds to 2nd receptor that serves as entry receptor
What does immune privileged mean?
areas are walled off from the immune system so very little, if any, immune cells patrol there
What is another way HSV is spread?
asymptomatic shedding in saliva or genital secretions w/o lesions
How can HSV be transferred most commonly from mother to baby?
at birth when the baby passes through infected maternal vaginal secretions
Why can't ssDNA viruses immediately copy their genomes?
at least 1 viral protein needs to be made b/c mRNA needs to be made first before anything else, but host cells can only do that with dsDNA
What type of RNA genome is inside the rotavirus viral core when it is newly made?
only (+) strand
Why does VZV infect differently in the skin?
b/c VZV has mannose-6P in its envelope, most cells it infects have mannose-6P receptors which cause newly formed virus variants to be directed towards large endoscopes where they become inactivated due to the acidity. Outer skin mannose-6P receptors are down regulated, so the new viral particles go to the extra cellular space and get released
Why do some latent viruses prefer immune-privileged sites?
b/c it is easier to escape immune surveillance
Why does immunization against Hep B virus reduce the risk of progression to a chronic form of the infection?
b/c it stimulates the IgG response against surface antigen
Why is Shingles rash painful?
b/c sensory neurons are involved
Why must dsRNA viruses package an RNA-dependent RNA polymerase inside of their viral capsid?
b/c the (+) of RNA in their genome cannot function as mRNA
Why can VSV infect so many types of cells?
b/c the receptor it uses is present on a lot of different cells types as it is an important receptor
What was latent infection process discovered with?
bacteriophage lambda
How does influenza enter host cell?
binding to sialic acid receptor and endocytosis
What is made when the ssDNA is copied?
both (-) and (+) strands are made
How does Hep B gain its envelope?
by budding into ER
How does most of the RNA get removed from Hep B DNA genome?
by the RNaseH activity of polymerase
Chronic HBV is linked to what?
cancer
What is the primary infection of VZV?
chickenpox
What group is most susceptible to B19?
children
Who is more commonly affected by HSV-1?
children
What age groups are typically infected by rotavirus?
children, mostly developing countries
What types of entry can herpesvirus use?
clathrin and caveolin independent endocytosis as well as membrane fusion
What happens when herpesvirus binds host cell receptor?
conformation change in several glycoproteins which induces a pH-dependent fusion w/ cell membrane; mediated by 4 glycoproteins
How is Ebola transmitted?
contact with body fluids of infected animals or people
What is Hep B's closed genome called?
covalently closed circular DNA
What is the last ditch effort of the immune system against Ebola?
cytokine storm
Where do poxviruses replicate?
cytoplasm
Where does Ebola replicate?
cytoplasm
Where does Measles replicate?
cytoplasm
Where does VSV replication take place?
cytoplasm
Explain process of rolling circle replication
host enzymes circularize viral dsDNA after enters the nucleus and then nicks the outside ring. The nick allows host cell DNA dependent DNA pol to come in and replicate. As it moves around the circle, it displaces original template strand and begins forming new DNA as it goes around. The first strand is open and available for binding extra polymerases to make DNA sets and other enzymes to fill gaps. Then, viral enzymes come in and begin cutting off genome at very precise places to get packaged.
What happens after Hep B genome is released into host?
host enzymes complete gap in genome and close the circle
When are consequences more serious with a chickenpox infection?
if you get it as an adult or infant
Who are most at risk for Measles and what complications are they at higher risk for?
immunocompromised, esp HIV/AIDS -pneumonia or encephalitis
What do some dsDNA viruses take advantage of and why?
immunoprivileged areas in the body to establish latency
Where do Pox viruses replicate?
in the cytoplasm
Where do mature herpesvirus glycoproteins embed?
in the trans-golgi network
Where are the surface glycoproteins inserted?
in to the ER membrane
What are some complications of Hep B?
increased atypical lymphocytes (unusually large due to stimulation from Ag), Jaundice, post-necrotic cirrhosis, hepatocellular carcinoma
What are the two reasons for the symptoms of influenza?
infect and inflammation
What happens as Hep B turns chronic?
inflammation mainly in portal tract of liver
What type of affect does Hep B have on the liver and how does it occur?
inflammation; virus causes infected cells to express strange proteins via MHC I which causes CD8+ T cells initiate apoptosis of infected cells leading to inflammation
Which virus causes one of the most widespread and deadly viral infections that occurs each year?
influenza
Which of the following is a unique characteristic of influenza replication in comparison to other RNA viruses?
influenza RNA going into the nucleus for transcription
Where are the gapped dsDNA genomes generated for Hep B?
inside the forming viral core
Where is Hep B pregenomic RNA reverse transcribed?
inside the viral capsid
How is the reovirus genome unique among RNA viruses?
it is double stranded with one (+) sense and one (-) sense strand
What receptor does rotavirus use?
it is unknown, but think sialic acid
What does VSV RdRp do when finished making segmented mRNA?
it makes full length (+) strand for conversion into full length (-) strand for replication
What happens to AAV when it enters the host cell?
it migrates to the nucleus by entering nuclear pore
What roles do AAV protein Rep 78/68 play?
it plays a role in copying of DNA genome for insertion into new particle and helps activate transcription of other AAV genes which produces more Rep 78/68 and structural proteins
Where does Hep B release its genome and how does it get there?
it releases genome into the host cell nucleus; the core particle travels via microtubules and binds to proteins w/in nuclear pore to release genome
What is the theory talked about in lecture about Ebola infections and the 2014 outbreak vs Ruskin, VA?
lab works in Ruskin, VA working with infected monkeys never got sick, but tested positive for Ebola Abs. The mutations seen in 2014 outbreak has scientists thinking that people are exposed Ebola, but immune system stops infection. However, the outbreak in 2014 showed mutated more virulent strains so ppl couldn't fight it off
What are the opposite of early genes?
late genes
What is produced during herpesvirus latency?
latency associated transcript is produced
What does the poxvirus genome look like?
linear, but the ends are fused forming a dumbbell shape
What is the Measles vaccine and how effective is it?
live, attenuated and 95-97%
What organ does Hep B infect?
liver
What does rolling circle replication produce in herpesvirus replication?
long viral genomes called concatemers
Which cell receptor does VSV use?
low density lipoprotein receptor
What are herpesviruses two phases of infection?
lytic-during initial infection and reactivation latent-inactive
What does herpesvirus concatemeric DNA produce?
mRNA of late genes which are transported to the cytoplasm and some packages into new particles
How does Ebola replicate, package and exit the cell?
mRNAs are transcribed by free ribosomes for non-structural proteins, RdRp (L) makes (+)RNA strand and replicates genome which gets encapsulated by N and VP30. Structural proteins are synthesized by ER ribosomes and sent to cell surface. Viral capsids are formed in cytoplasm and transferred by unique lipid rafts mechs to area with embedded proteins to bud off
What does the viral category of dependovirus mean?
means these viruses can't replicate in host cell w/o the help of another virus
What are some treatments of Measles?
medicine for super infections, pain relief and hydration
What is the possible illness of EBV?
mononucleosis
What are some unique symptoms in immunocompromised individuals?
more frequent reactivation, more severe symptoms, and a wider range of symptoms such as lesions of the esophagus and lungs
What cells are the first infected during HSV primary infection?
mucocilary epithelial cells
How does type A influenza mutate strains?
mutates its H/N glycoproteins during replication and allows daughter viruses to form slightly differently; genetic drift
What two glycoproteins are on the surface of influenza?
neuraminidase and hemagglutinin
How does influenza bud off host cell?
neuraminidase cleaves sialic acid so viral particles do not attach to receptors and enter the cell again
What type of cells rarely divide?
neurons, heart cells and lung cells
What happens to Hep B RNA after it is made?
non structural RNAs go to cytoplasm to get translated by free ribosomes and structural proteins go to ER ribosomes
Where does influenza replication take place?
nucleus
Where does rolling circle replication occur?
nucleus
What are the symptoms of oral primary infection of HSV-1?
often asymptomatic, but lesions of gum, palate, tongue, lip or facial area, fever, enlarged lymph nodes
How is HSV treated?
often resolves w/o treatments, but antiviral drugs like acyclovir, valacyclovir or famciclovir to reduce pain and speed healing
When does reactivation of VZV occur and why then?
old age, as cellular immunity wanes, or immunosuppressed
What are the first cells Measles infects?
once virus gets into mucosa, quickly infects epithelial cells in trachea/bronchi
Explain how poxvirus replicates genome
one strand nicked ny viral enzyme @ inverted terminal repeat sequence which allows virally encoded polymerase to come in and bind the end of the DNA molecule. Polymerase binds and duplicates what was once folded which causes the strands to bind upon themselves forming two circular ends on one side. This opens another place for DNA pol to bind and it copies the length of DNA until comes to loop @ end, copies around loop and continues until entire strand is done. Lastly, viral enzyme separates by nicking opposite end of genome
What is present at the window phase of HBV?
only IgM core Ab detectable
