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Virology Review 2
Large & Small Nuclear DNA Viruses
| Question | Answer |
|---|---|
| Replication is exclusively nuclear | Replication of these viruses is very dependent on cellular factors |
| Examples of Small Nuclear DNA viruses | Parvovirus; Papillomavirus; Polyomavirus |
| Examples of Large Nuclear DNA viruses | Adenovirus; Herpesvirus |
| Replication is dependent on Cellular DdDp & DdRp | Replication of Small DNA viruses |
| Small DNA viruses infect cells... | by inducing the cell into S phase (DNA synthesis pahse) OR they must find cells already going through S phase |
| Polyomavirus & Pappilomavirus infect cells ... | these viruses infect cells by inducing them into S phase |
| Parvovirus infect cells... | this virus infects cells that are already going through S phase (can't induce) |
| Small DNA viruses may integrate their viral genome into the host chromosomes | Small DNA viruses may integrate their viral genome into the host chromosomes |
| Efficiency/Economy with which Small DNA virus genomes are organized | the cis-signals for transcription, DNA replication, RNA processing, & translation are concentrated and often overlap |
| Parvovirus Structure | Small Single-Stranded DNA virus, Replicate in Nucleus, Icosahedral Symmetry, Non-Enveloped |
| Autonomous Parvoviruses | This type of Parvovirus only replicates in already dividing cells |
| Dependovirus | This type of virus needs a helper virus |
| DNA must become ds before transcription | DNA must become ds before transcription |
| Adeno-associated Virus (AAV) | A dependovirus. It is an incomplete virus that needs a co-infected cell. Site specific-integration |
| Parvovirus Genome Structure | Genome is flanked by 2 inverted terminal repeats. Contains 2 ORFs, 6 major RNA species, 3 promototers & alternative splicing signals. It has a ss region, the ends are ds (loop) |
| Parvovirus ORFs: ref & cap | repORF encodes regulatory proteins (replication, gene expression, packaging). capORF encodes for structural proteins |
| Papillomavirus Structure | Small, icosahedral capsid, non-enveloped, circular dsDNA that is associated with histones |
| Papillomavirus genotypes are considered distinct if... | if the nt sequence of specific regions of viral genome differ by 10+% |
| Papillomaviruses infect either _________ or __________ of a person | Infect either mucosa or skin |
| Papillomavirus genome structure | 2 transcriptional promoters & 2 polyadenylation signals (early & late) on the same DNA strand |
| Papillomavirus Early proteins | E1-E7 stimulate cell proliferation & enable viral DNA replication |
| Papillomavirus Late proteins | L1 & L2 form the capsid |
| Papillomavirus: splicing? | Splicing generates 10+ different mRNAs |
| Polyomavirus Features | small, icosahedral capsid, non-enveloped, dsDNA associated with histones, lytic & non-lytic cycle |
| Members of Polyomavirus Family | SV40 virus, BK virus, JC virus |
| Role of Polyomaviruses in research | important model used to study basic mechanisms of tumorogenesis in mammals, mammalian RNA synthesis & processing, SNA replication, & signal transduction |
| Polyomavirus enters the cell via... | Endocytosis (bidning to MHC-1) |
| Polyomavirus uncoating occurs... | in the nucleus |
| Polyomavirus gene organization | Organized in 2 divergent transcription subunits, only 1 ORF |
| Polyomavirus gene expression Early phase | Proteins needed for DNA replication; Regulatory proteins (non-structural); Often proteins which alter host cell |
| Papillomavirus activity in nucleus | Genome replication, nucleocapsid formation, & virion maturation |
| What is the Large T antigen? | a large, multifunctional protein that is involved in cellular process like transcriptional activation & repression, differentiation, and stimulation of cell cycle |
| What does Large T antigen interact with? | it interacts with p53 and pRb |
| What does Small T antigen interact with? | it interacts with cellular phophatase, PP2A |
| Function of large T-antigen in DNA replication | Recruit DNA polymerase |
| Parvovirus Genome Structure, single & double stranded? | Single stranded region, with ITR double-stranded ends. The ds loop acts as a primre for DNA synthesis |
| Polyomavirus, replication occurs when? | replication occurs after early gene expression and before late protein expression |
| Polyomavirus & Host RNA polymerase | Host RNApolym is recruited to promoter & makes 1` transcript |
| Polyomavirus & Alternative Splicing | The 1` transcript is alternatively spliced producing (1st) Small T antigen and (2nd) Large T antigen |
| Polyomavirus & 1 ORF | Has 1 ORF that makes 2 products, efficient for small viruses |
| Large T binds to ______________________ and functions as a ___________________ and recruits DNA polymerase during DNA synthesis. | large T binds to an ORIGIN OF REPLICATION and functions as a REPLICATION PROTEIN and recruits DNA polymerase during DNA synthesis. |
| Large T recognizes a ______________ and functions as a _________________ during Late RNA synthesis. | Large T recognizes a PROMOTER and functions as a TRANSCRIPTION FACTOR during Late RNA synthesis. |
| VP2 and VP3 are made via... | made by a 2nd alternative splicing of 1` transcript |
| VP1 is made via... | made by shifting, changing the start of the reading frame in the 1` transcript |
| Function of Large T antigen besides in DNA rep | Increased transcription of late genes; Decreased transcription of early genes; cellular transformation |
| Function of Large T antigen is pahse progression | Amount of Large T may tell the cell to slow down early transcription to move to next pahse, lower affinity binding site |
| Polyomavirus Assembly & Maturation | Occurs in Nucleus simultaneously |
| Polyomavirus Assembly | Capsid proteins in cytoplasm are moved to nucleus where they assemble with viral DNA (histones) |
| Inclusion Bodies | Large number of capsides accumulated in nucleus |
| Polyomavirus Release | Released via Cell Lysis (b/c its non-enveloped) |
| Polyomavirus - Host cell provides what? | DNA synthesis machinery, RNA synthesis machinery, & Histones |
| Polyomavirus 2 Types of Infection | Productive (lytic) infection & Non-productive (abortive) infection |
| Adenovirus Structure | small, non-enveloped, icoasahedral |
| Adenovirus DNA | linear, Double-stranded DNA, genome NOT associated with histones |
| Adenovirus Cell Entry | Fibers bind to cell surface recptors, Endocytosis, Lyse endosomes |
| Adenovirus Uncoating | Occurs in steps near nucleus |
| Adenovirus Nuclear Entry | DNA released into nucleus through nuclear pore |
| Adenovirus mRNA synthesis: Immediate Early | IE-A and IE-B |
| Adenovirus mRNA synthesis: Early | genes scattered |
| Adenovirus Early mRNA promoter | many,not 1 single promotor, clusters, can make things only when needed |
| Adenovirus early proteins | proteins needed for transcription of other early mRNAS (E1a gene product), for DNA synthesis, that alter expression of host genes, that interfere with host anti-viral defenses, and that interfere with cell cycle regulation |
| Adenovirus: DNA polymerase | Encodes for its own DNA polymerase! Does not use the host's. |
| Adenovirus: DNA replication | Displace strand, similar to semi-conservative |
| Adenovirus: Terminal Protein (TP) | Functions as a primer, recruites DNA polymerase ; convalently linked to 5` end of all viral ssDNA strands |
| Adenovirus: ss Binding protein | binds to DNA strands during replication to protect it |
| Adenovirus: Late mRNAs | code for structural proteins, late genes in block |
| Adenovirus: Primary transcript (only 1 is made) | is processed & spliced A LOT to generate various monocistronic mRNAs |
| Adenovirus: Late transcription | Only 1 promoter driving expression of ALL late proteins |
| Adenovirus: Steps of Processing the Primary transcript | Cut at poly(A) site, polyadenylate to add tail, splicing, intron removal |
| Adenovirus: Assembly & Maturation | Occurs in nucleus simultaneously |
| Adenovirus: Release | Cell Lysis |
| Adenovirus: Host cell provides what? | DNA synthesis accesory factors, RNA synthesis & modification enzymes. (does not provide polymerase or packaging proteins!) |
| Adenovirus: Early mRNA processing | processed by host cell capping, methylation, polyadenylation, and splicing enzyme systems |
| Herpesvirus Structure | Icosahedral nucleopcapsid surrounded by tegument & a liped bilayer with peplomers; enveloped. Also contains cellular components. |
| Peplomers | The glycoprotein spikes located on the lipid bilayer of a herpesvirus that are important for attachment |
| HSV 1 | Herpes Simplex Virus Type 1 - cold sores |
| HSV 2 | Herpes Simplex Virus Type 2 - genital |
| Herpesvirus Type 8 | Kaposi's sarcoma |
| Other Typres of Herpesvirus | Varicella zoster virus (chickenpox), Epstein-Barr virus (infectios mono), Burkitt's lymphoma |
| Herpesvirus: Genome | Large, linear, double-stranded DNA |
| Herpesvirus Attchment & Penetration | Fusion with cell membrane, release of genome into cell, leaves footprint on cell membrane |
| Synctia Formation | Footprint has viral attachment proteins so if infected cell gets near uninfected, can bind together and form synctia |
| Herpesvirus: Immediate Early - alpha-mRNAs | stimulated by cellular DNA-dependent RNA-polymerase. a virion protein that interacts with host transcription factor & increases transcription from alpha promoters |
| Herpesvirus: Alpha proteins | are made in the cytoplasm but move back to nucleus act as transcription factors for bet-mRNAs. Also enable beta promoters to be recognized |
| Herpesvirus: Early - beta-mRNAs | encode VIRAL DNA-dependent DNA-polymerase, DNA binding proteins, thymidine kinase, ribonucleotide reductase |
| Herpesvirus: Beta proteins | synthesis results in decrease of alpha-mRNA synhtesis. |
| Herpesvirus: Beta proteins & Chemo | They are virally encoded enzymes, so they are good targets for viral chemotherapy |
| Herpesvirus: Uncoating | Partially uncoaded when enter cell, fully uncaoted when entering nucleus |
| Herpesvirus: DNA replication | Variant form of rolling circle mechanism. DNA may recircularize in cell, viral proteins required. Repetitive sequences at ends of viral genome are involved with circulization and packaging. |
| Herpesvirus: Late (gamma) gene transcription | occurs after DNA replication & outside of nucleus. proteins are then transported INTO the nucleus for packaging |
| Gamma-proteins | mainly structural, one must be packaged in the virus to intiate the first step of alpha-gene transcription |
| Herpesvirus: Tegument | an amorphous proteinaceous substance that surrounds the herpes nucleocapside. It contains 8+ viral proteins |
| Herpesvirus: 5 glycoproteins that participate in cell entry | gB, gC, gD, gH, and gL [B,H, & L are structurally conserved among all herpesviruses & essential to entry) |
| Herpesvirus: Coreceptors | HVEM (herpes virus entrey mediator) and Nectin-1 & nectin-2 |
| Herpesvirus: Virion Host Shutoff Protein (vhs) | viral protein that participates with rapid degradtion of cellular mRNAs, causing a shutoff of host protein synthesis |
| Herpesvirus: VP16 | binds to DNA & is an activator of transcription/expression of alpha-genes |
| Herpesvirus- alpha-genes | encode DNA binding proteins that play a role in viral transcription |
| Herpesvirus- beta-genes | encode DNA replication & more transcription factors |
| Herpesvirus: Assembly in Nucleus | capsid assembly occurs in nucleus after gamma-proteins are synthesized. DNA concatemers are cleaved into monmers & packaged as well. |
| Herpesvirus: Release from Nucleus -> | nucleocapsid/tegument bud out of nucleus, budding from ER lumen, cell lysis |
| Herpesvirus: Notes on Replication - gene blocks | No obvious early/late gene blocks |
| Herpesvirus: Notes on Replication - independence | More independent than other small viruses & because more independent, harder to target with drugs |
| ALPHA Herpesviruses: 2 Types | 1. Herpes Simplex Virus (HSV) ``` 2. Varicella Zoster Virus (VZV) |
| Herpes Simplex Virus: Productive Infection | Lytic replication in epithelial cells - Retrograde transport moves capsid up axon - latent HSV episome (NOT-integrated) lies in ganglia |
| Episomes | Circular DNA that replicates independently of the cell's nucleus |
| Latency Associated Transcripts (LATS) | Limited group of viral genes that are expressed during latent stage |
| Varicella Zoster Virus (VZV): Chickenpox | The only herpesvirus that spreads preson to person by coughing or sneezing |
| Varicella Zoster Virus (VZV): Shingles | latent chickenpox becomes reactivated >60yo. Can NOT be spread person to person |
| BETA Herpesvirus | Cytomegalovirus |
| Cytomegalovirus (CMV) | an opportunistic infection of ImComp pple. Causes 21% of Mono cases |
| GAMMA Herpesvirus | Epstein-Barr Virus |
| Epstein-Barr Virus (EBV) | Causes 79% of mono cases; associated with Burkitt's Lymphoma |
| Acyclovir | Most common Rx for Herpesvirus; Guanosine analog, can be used for long-term prophylaxis, action limited to virally-infected cells |
| Acyclovir Mechanism of Action | Converted to ACG-monophasphate by Herpesvirus Thymidine Kinase (TK). 3 phosphates added, 1st by cellular or viral TK, 2nd & 3rd by cellular kinases |
| WHY DOES HERPES SIMPLEX CODE FOR ITS OWN THYMIDINE KINASE? | HSV brings it’s own kinase, so it can increase the pool of phosphorylated nucleosides and can grow in non-dividing cells |
| What is Thmydine kinase? | “Thymidine kinase” is a misnomer |
Created by:
lbr9349
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