World of viruses - intense protein/DNA Flashcards
Which viruses encode dUTPase?
Herpes and poxvirues
Some retroviruses
Which viruses encode TK enzyme?
Herpes and poxviruses
What are the guanosine nucleoside analogues?
Acyclovir and gancyclovir
Which viruses encode UNG? and what does it do?
Herpes and poxviruses
Excises misincorporated uracil to an abasic site so it can be repaired by cellular enzymes
Which viruses encode viral ribonucleoreductases and what do they do?
Herpes and poxviruses
Increase pool of dNTPs by removing -OH from NTPs
What is the cellular enzyme which deaminates cytosine
APOBEC3G
Which viral protein blocks APOBEC3G
HIV Vif
Which enzyme changes adenosine into inosine
ADAR
Which base does inosine base pair with
Cytidine would normally have been A base pairing with U
Which virus requires ADAR editing for production of a larger antigen
Hep Delta virus
If 4E-BP is phosphorylated does it bind eIF4E?
No cannot bind
If 4E-BP is not phosphorylated can it bind eIF4E
Yes can bind and block translation
Which 5 viruses activate P13K? and does this inhibit or activate translation?
HCV HPV16 EBV HIV-1 KSHV
Activates translation
Which 3 viruses block TSC? and does this active or inhibit translation?
HIV-1
HCMV
HPV16
Activates
Which virus stimulates mTORC1 and does this stimulate or inhibit translation?
West Nile virus
Stimulates
Which 2 viruses increases 4E-BP i.e. un-P form and does this active/inhibit translation?
VSV
Polyomavirus
Inhibit’s translation as 4E-BP can bind to eIF4E
Which virus stimulates 4E-BP-P form? and does this stimulate/inhibit translation?
EMCV
Stimulates
Which 4 viruses and the proteins cleave eIF4G?
Picornavirus (polio and rhino) - 2A protease
FMDV leader protease
Calicivirus 3C protease
Retrovirus (HIV, HTLV) protease
Which 3 viruses/proteins interact with eIF4G?
Influenza - NS1
Adenovirus - 100K
Rotavirus - nsp3
Which virus protein physically binds to eIF4G and prevents translation?
Influenza NS1
Which virus protein binds to eIF4G and excludes MNK1 which prevents P of eIF4E
Adenovirus 100K
Which virus protein binds to eIF4G and prevent interactions with PABP so only get one round of translation?
Rotavirus nsp3
Which 3 viral proteases cleave PABP?
Picornaviruses 2A and 3C proteases
Calicivirus 3C protease
Lentiviruses (e.g. HIV) protease
Which virus protein is an mRNA specific endonuclease which interacts with eIF4A and degrades mRNA?
Herpes simplex virus vhs protein (UL41)
Which 3 viruses cap snatch?
Vaccinia virus
Influenza virus
Hanta virus
Which virus activates a cellular pathway to degrade PKR?
Poliovirus
Which 4 virus proteins are dsRNA binding proteins
Vaccinia E3L
Reovirus delta3
Rotavirus NSP3
Influenza NS1
Which 3 viruses produce short dsRNA which prevents PKR from dimerising?
Adenovirus VAI, EBV EBER and HIV Tar
Which virus protein prevents PKR dimerisation?
Hep C NS5A
Which 3 virus proteins act as pseudosubstrates for PKR?
Vaccinia K3L protein - Ala instead of serine so no OH
HSV VS11 protein
HIV Tat protein
Which virus has a type 1 IRES and what factors does it require?
Poliovirus
Requires C-term of eIF4G with eIF5, 2, 4A and MNK1
40S ribosome
Which virus has a type 3 IRES and what factors does it require?
HCV
eIF3, 40S ribosome, eIF5, 2
Does not require eIF4F
Which virus has a VPg protein which acts as a cap analogue and binds to eIF4G an eIF3
Caliciviruses
What are the 10 proteins produced from the HCV polyprotein?
Non-structural: Core, E1, E2, p7
Structural: NS2, NS3, NS4A, NS4A, NS5A, NS5B
Is HCV a enveloped virus?
Yes
Is Polio a enveloped virus?
No
Which 4 viruses can block autophagy by binding to Beclin
Herpesvirus gamma-34.5
Kaposi’s sarcoma herpes virus HSHV M11
HCMV TRS1
HIV nef
What are the two ways apoptosis can be activated?
Intrinsic - inappropriate DNA synthesis or shut off of protein synthesis
Extrinically - cytokines, NK cells, CTL
Where is the FAS ligand expressed?
Cytotoxic T cells, NK cells
Which 5 virus proteins target p53 for degradation?
Adenovirus E1B 55K, E4-Orf6 HPV E6 SV40 large T antigen Hep B pX Hep C NS3 and NS5A
Which 4 virus proteins target pRb for degradation?
Adenovirus E1A
HPV E7
SV40 large T antigen
Hep C NS5B
What 3 things make up the apoptosome?
Cytochrome C, Apaf-1 and dATP
Which caspcases are activated by the apoptosome in mitochondrial apoptosis?
Pro-caspase 9 –> caspase 9 which then causes pro-caspase 3 –> caspase 3 –>cell death
Which 4 virus proteins are BCL-2 homologues?
Adenovirus E1B/19K
Herpesvirus EBV BHRF1
African swine fever virus A179L
Vaccinia virus N1 and F1L
Is BCL-2 antiapoptotic or proapoptotic?
Anti - keeps the pore in the mitochondria closed
Which virus produces untranslated RNA which has a novel interaction with complex 1? And what does this do?
HCMV - beta2.7 RNA binds to complex 1 in the mitochondria which stabilizes it can protects it from metabolic stress
Which caspase is activates in the ER stress response?
Ca2+ release causes activation of caspase 12
Does HCV block the ER stress response?
No doesn’t seem to care - RT-PCR showed the short form of Xbp-1 showing UPR to be activated
Which 2 viruses block the activity of PERK?
Dengue and HSV
Which virus blocks the activation of ATF-6?
HCMV
Do all 3 arms of the UPR need to be active to induce an ER stress response?
No hence why viruses just block one
Which caspases are activated in extrinsic apoptosis?
Caspase 8 –> caspase 3
What are two death domain containing proteins?
FADD or MORT
What type of genome is adenovirus?
dsDNA which produces different transcripts
Which adenovirus transcript blocks extrinsic apoptosis?
E3 - 10.4K + 14.5K = RID complex
6.7K and 14.7K
Which two transcripts in adenovirus make the RID complex?
10.4K and 14.5K
Which viral complex targets FAS and TNF receptors into endosomes then lysosomes?
RID complex of adenovirus
Which adenovirus protein targets caspase 8 and prevents its function?
14.7K
Which viral proteins prevent cPLA2 from going to the cell surface?
14.7K and RID complex of adenovirus
Which virus endocytoses TRAIL?
Adenovirus 6.7K and RID complex
Which 2 viral proteins have homology to death domains?
vFLIPs
Molluscum contralosum - Pox virus benign cutaneous lesions - MC159 protein
gamma-herpes virus - Kaposis sarcoma herpesvirus K13
Which 3 viral proteins are serine protease inhibitors which inhibit caspases?
Cowpox CrmA
Rabbitpox SPI-1
Vaccinia SPI-2
Which viral protein specifically inhibits caspase 9?
Vaccinia F1L (BCL-2 inhibitor)
Which 2 viral proteins specifically inhibit caspase 3?
Mousepox p28 and rabbitpox N1R
Which DNA virus inhibits caspases?
Adenovirus E3-14.7K - caspase 8
What is the hallmark of late-stage apoptosis?
Phosphatidylserine (PS) on the outer leaflet of the cell surface.
Normally on the inner but ATP2C Flippase normally flips back but in apoptotic cells it is cleaved by caspases
What is the direct receptor of PS
T-cell immunoglobulin and mucin receptor (TIM)
What is the receptor and bridging molecule for indirect receptor of PS
AXL receptor and GAS6 bridging molecule
When PS binds to other cells what does it stimulate the production of to prevent an immune response?
Active TFs for genes to block the inflammatory response and the innate immune response
Produce cytokines e.g. IL10 which are anti-inflammatory and produces SOCs proteins which inhibit the immune response
Which enveloped viruses use membranes contain PS?
Dengue - buds into ER and picks up a membrane - clathrin-coated endocytosis
Vaccina - picks up a cellular membrane as it is released - macropinocytotic entry as big virus
Ebola - buds from lipid rafts on the surface of infected cell containing PS and macropinocytotic entry into other cells
Which non-enveloped virus has a GAS6 mimic?
SV40 VP1 protein
Which non-enveloped viruses get incorporated into membrane structures despite not being enveloped?
Hep A and picornaviruses like polio
HepA get trafficked in MVBs and released by exosomes which cells release all the time for trafficking between cells
Picornaviruses auto autophagosomes to replicate on and get to get incorporated into these double-membraned vesicles which are autophagosome-like and the outer membrane fuses via PS
How many domains are there is NS5A?
3 domains: 1, 2 and 3
Crystal structure of 1 but 2 and 3 are highly disordered
Which other HCV proteins does NS5A directly interact with?
NS5B and NS4A
Which proteins in the EGF signally pathway does NS5A bind too?
Binds Grb2 SH3 domain with its P2 (proline motif) which blocks downstream signalling to Ras
What is the motif for binding to SH3 domains?
Polyproline motif - PxxPxR
What happens with NS5A binds to the p85 subunit of PI3K?
Activates PI3K which generates PIP3 from PIP2 which allows it to bind to PH domain proteins such as Akt.
Upon binding induces a conformation change which causes PH domain to move and get activation of Akt which is a kinase and P’s BAD. BAD-P blocks the mitochondrial permeability pore and blocks apoptosis
Which virus binds to the p110 subunit of PI3K?
HBV
Which 3 viruses bind to the p85 subunit of PI3K?
Hep C NS5A
EBV LMP1
Murine PyV MT
Which 6 viruses target the PI3K pathway and stimulate the anti-apoptotic response?
EBV LMP2A HIV-1 Tat HPV16 E5 Flaviviruses RSV Rubella
Does NS5A block P of Kv2.1?
Yes as a response to oxidative stress
Is Kv2.1 a proapoptotic or antiapoptotic channel?
Pro - pumping out K+ ions reduces [K+] leading to caspase 3 and 9 activation and apoptosis
What is the drug which targets NS5A?
Daclatasvir
Which virus protein is a functional homologue of NS5A?
CHIKV virus nsp3
