Exam III: Lecture 11 Flashcards
There are over ___ kinds of herpesvirus, all infecting vertebrates
100
What is the genome of herpesvirus? Type, length, how many encoded proteins, episome, shape of nucleocapsid
ds DNA (120-230 kb) Linear 30 encoded proteins + cellular proteins Episome exists outside of the chromosome Icosahedral nucleocapsid
HV has a wide host range (amphibians, birds, mammals), but each virus restricts itself to how many hosts?
one
Is HV a new or old virus?
Ancient and co-evolved with their hosts
What are the 3 classes of HV?
- alpha
- beta
- gamma
AlphaHV: host range, pace of reproductive cycle, latent in what cells, lytic in what cells
Broad host range
Quick reproductive cycle
Latent in sensory ganglia Lytic infection in epideral cells
betaHV: host range, pace of reproductive cycle, latent in what cells, what do infected cells look like?
Restricted host range
Long infection cycle
Latent in secretory cells, lymphoreticular cells, kidney cells
Infected cells become enlarged (cytomegaly)
What is an example of a alphaHV?
Vericella Zostar Virus (VZV) > chicken pox
What is an example of a betaHV?
Cytomegalovirus
gammaHV; host range, pace of reproductive cycle, infection occurs in what cells
Restricted host range
Infect lymphoblastoid cells, B cell, T cells
Infection is frequently latent
What is an example of gammaHV?
Epstein-bar Virus
What is the cause of 90% of all genital herpes cases in the US?
HSV-2
New infections of HSV-2 occur at what rate?
1 million new cases/year
The majority of HSV-2 infections are unrecognized, undiagnosed, and untreated
True
What is the only herpes virus to spread via coughing/sneezing?
Chickenpox = VZV
When do symptoms of chickenpox (VZV) develop?
10-21 days after contact with an infected person
VZV infects what?
The skin or mucosa of the respiratory tract and progresses through the blood and lymphatic system to the cells of the reticulo-endothelial system
What is a unique feature about Herpesviridae genome structure? (2)
Is highly conserved (shows it stemmed from one ancestor and then adapted)
Has repeat regions (A, A’)
HSV entry
HSV binds to heparan sulfate and TNFR superfamily member 14
Talk me through HSV-I lifecycle
HSV-I > binds to heparan sulfate > enters cell > viral particle nuclear membrane > releases genome + VP16 (VP16 = TF > Imediate early genes/alphagenes = TF > Early genes/betagenes > gamma/Late genes) > genome circularizes > genome replication occurs > genome is produced linearly
Why is having IE > E > L genes advantageous to us?
There are multiple points of regulation is HSV
HSV DNA replication uses the rolling circle mechanism
True
Tell me about rolling circle replication
Seperate the two strands > primers > DNA polymerase > daughter strand gets pushed out of genome = new strand is linear
BUT there is no stop code so the daughter strand is actually multiple copies long = concatimer > concatimer must be cleaved
Tell me about latent infection of HSV-I
HSV-I infects nerve cell (lytic infection is inhibited in nerve cells) > retrograde transport to axon > nucleus > goes quiet > produces only latent associated trascripts (regulatory RNAase) > trigger > virus expresses genes > back to synapse > bud out of synapse > infect epithelial cells > lytic infection > spread
Tell me about HSV-I egress?
genome reassembles in nucleus > buds out of nucleus = takes part of the nuclear membrane > fuses with perinuclear membrane > spits out nakes viurs > through the golgi membrane > goes to surface of cell > buds out/2 adjacent cells fuse
5-10 copies of the viral DNA in the form of __________ stay in the sensory ganglia
Circular episomes
Reactivation of HSV in neurons can cause what?
Nerve pain
What are possible triggers for HSV?
- Fever
- Menstruation
- UV
- Stress
What is the physical sign HSV has been reactivated?
Cold sore on lip = at the end of the nerve in the face = where HSV buds out
What happened in the case of the man with the crazy rash on his face?
HSV budded out along the axon instead of just at the synapse
What is Acyclovir? Which herpesviruses does it treat?
Guanosien analog
Treats HSV-I, HSV-II, VZV
What type of genome does Adenovirus have? # bp? Enveloped?
dsDNA
35,000-40,000 bp
linear
non-enveloped
Where/when was adenovirus first isolated?
1953
Military recruits
How many serotypes of adenovirus infect humans? What is the implication of this?
51
You can get infected over and over and over again
What makes a virus a different serotype?
If it resists neutralization by antibodies against another serotype
Human adenoviruses can cause tumors in rodents; what is the mechanism of cell cycle deregulation?
E1A and E1B
Talk me through the viral attachment and penetration of adenovirus
Adenovirus binds to CAR (coxsackievirus adenovirus receptor) > binds to secondary receptor integrins > receptor-mediated endocytosis
What is a unique feature about the viral genome of adenovirus?
It has a terminal protein (TP) that sticks out from a penton base = linked covalently to the 5’ end
The virus comes with a protein attached to the genome
How many genes does the adenovirus virion encode for? How many proteins does adenovirus encode for?
11 genes
Huge number!
With 35,000-40,000 bp and splicing you have tons of isoforms of those proteins
Is VA RNA of adenovirus tranlated?
No
Adenoviral genome is transcribed by ____
RNA pol II
What are the 5 early promoters seen in adenoviral genome? What do they do?
- E1A (transactivator of gene expression & oncogenes that activate S phase)
- E1B (transactivator of gene expression & oncogenes that activate S phase)
- E2 (viral replication)
- E3 (modulates host response by blocking MHC maturation)
- E4 (transription and replication)
What does E1A promote? inhibit?
Promotes p53 by sequestering PI4Arf = binds MDM2 > p53 is stabalized»_space; phagocytosis and viral entry into macrophages
Inhibits Rb
What does E1B suppress?
Apoptosis
E1A stimulates the cell cycle and apoptosis, E1B inhibits apoptosis. How would this affect the virus life cycle?
Perhaps E1B comes first or is in full force while the virus replicates and then E1A promotes apoptosis and cell cycle in order to escape from the cell
Talk me through Adenoviral DNA replication
Replicaton begins at an OH group provided by the preterminal protein (PTP) > genom is attached to PTP > 2 strands seperated by ssDBP > DNA polymerase binds to 5’ end with OH group > extends off OH and protein gets incorporated > circularizes > PTP gets cleaved to form TP > second strand gets replicated > end with 2 linear strands with TP
Parvovirus genome: how many kb? neg or pos? shape?
ssDNA
5 kb
usually, neg strang
icosahedral
Parvovirus a member of what genus? What is unique about this genus?
Dependovirus
Can only replicate in cells that are infected by adenovirus or herpesvirus
More than ___% of humans have antibodies against dependoviruses
90
What are Adeno-associated viruses?
AAV needs a helper vris to replicate
AAV is a dependovirus
In the absence of a helper, what does AAV do?
Establish a latent infection in chromosome 19 using Rep 78/68 in low levels > upon infection of the cell by adenovirus/herpesvirus the AAV reactivates
Why might AAV be beneficial?
Gets activated in cancer cells > causes lytic infection > cell death = protects against the formation of tumors
Does AAV cause disease?
No
How does adenovirus cause the reactivation of AAV? (be specific)
Adenovirus protiens (E1A, E1B, E4) > transactivate the Rep proteins Rep 78/68 > replication of viral genome
What are the two classes of genes in an AAV?
- Replicase (Rep 78/68/52/40)
2. Structural proteins (VP1, VP2, VP3)
Talk me through the replication of viral genome of AAV
The ssDNA folds into a hairpin > there is an exposed OH group which serves as the starting point > goes until the other end > hairpin part unwinds > finish up > then there is a cleavage on the other end of the hairpin revealing an OH group > serves as the start to replication > end up with a hybrid genome
Parvovirus B19 belongs to what genus? Infects what cells? What pathology does it cause?
Erythrovirus
Infects human erythroid cells
‘Slapped Cheek’, joint inflammation, can induce abortion
Parvovirus B19 is ____ leading to death of the infected cell
Cytolytic
Over ___% of adults have antibodies against Parvovirus B19
50
What is Parvovirus B19 AKA?
5th disease
