Viral Pathogens Flashcards
What are the different viral structures?
→helical
→icosahedral
→complex virus
→enveloped virus
What are the 4 structures of viral genome?
→Single-stranded RNA (ssRNA) →Double-stranded RNA (dsRNA) →Single-stranded DNA (ssDNA)
→Double-stranded RNA (dsDNA)
In what sense, can viral genomes be encoded?
→both 5’3’ and 3’5’
What is the Baltimore classification?
→classification system that places viruses into one of seven groups depending on a combination of their nucleic acid (DNA or RNA), strandedness (single-stranded or double-stranded), Sense, and method of replication
What is group 1 of the BCS?
→dsDNA
→+and -
What is group 2 of the BCS?
→ssDNA viruses (+)sense DNA
What is group 3 of the BCS?
→dsRNA viruses
What is group 4 of the BCS?
→(+)ssRNA viruses (+)sense RNA
What is group 5 of the BCS?
→(−)ssRNA viruses (−)sense RNA
What is group 6 of BCS?
→ssRNA-RT viruses (+)sense RNA with DNA intermediate in life-cycle
What is group 7 of BCS?
→dsDNA-RT viruses
What does the outer envelope of HIV consist of?
→lipid bilayer with protruding Env spikes (heterotrimers of SU3TM3)
What lies in the envelope of HIV?
→Gag proteins
What coats the RNA genome?
→nucleocapsid
What does the core of the HIV virus contain?
→two genomic RNA strands (plus strand),
→tRNALys3,
→~50 copies of each viral enzyme: protease, integrase and reverse transcriptase
What are the three polyproteins retroviruses synthesise?
→Gag
→Pol
→Env
What are Gag polyproteins?
→group specific antigen
→viral core proteins
What are Pol polyproteins?
→viral enzymes
→RT, IN,PR
What are Env polyproteins?
→envelope glycoprotein
What are the HIV-1 regulatory accessory proteins?
→Tat - potent activator of viral transcription
→Rev - mediates unspliced RNA nuclear export
→Vif - critical regulator of virus infectivity
→Nef - immune modulator, T-cell activation, virus spread (?)
→Vpu - immune modulator, virus release
→Vpr - cell cycle, virus nuclear impor
What are the components of HIV RNA?
→Trans-activation response element →Rev responsive element →5 and 3 UTR →Repeat →Long Terminal repeat
What does the Env polyprotein in HIV-1 consist of?
→a trimer of gp41 and gp120 peptide subunits
→covered with glycans
What are glycans?
→post translational modification eg carbohydrates
What does HIV-1 entry require?
→CD4
→a chemokine receptor (CCR5/CXCR4)
What is HIV-1 tropic for?
→for CD4 expressing cells such as helper T cells and macrophages
What does loss of CD4 result in?
→immunodeficiency (AIDS).
Why does HIV-1 replicate in the nucleus?
→nucleic acid present
How does HIV-1 gain entry into the nucleus after fusion?
→uses microtubule network
What allows the core to be deposited into the nucleus?
→Viral core has capsid modifications
What are the components of RT?
→heterodimer of p66 and p51 subunits
What are the roles of p66 and p51?
→Catalytic properties are in p66 subunit,
→p51 serves structural role
→lacks RNAse H domain
What are the three enzymatic activities of RT?
→RNA-dependent DNA polymerase
→RNAse H (cleaves RNA from RNA/DNA hybrid)
→DNA-dependent DNA polymerase
How does the viral genome integrate into host genome?
→integrase enzymes
→recognise flanking sequences
→bends host DNA
→brings together host and viral DNA
What is the function of LEDGF/P57 in viral integration?
→binds HIV-1 integrase and facilitates targeting to chromatin
How doe ensure we get preferential transcription?
→Viral Tat protein- binds specifically to viral RNA and enhance RNA pol II
What produces different mRNAs for viral proteins?
→HIV-1provirus
What protein mediates nuclear export of unspliced RNA?
→ HIV-1 Rev
→binds to RRE region
Promotes viral export over cellular RNA export
→has specificity
What does HIV-1 Rev protein interact with?
→Crm1 and the RRE RNA
What is the purpose of unspliced HIV-1 mRNA?
→for Gag and Gag-Pol proteins
Why does unspliced viral RNA dimerise?
→allows packing of two genomes
→kissing loop complex
What is Gag-pol protein generated by?
→1 ribosomal frameshifting induced by a ‘slippery’ sequence
→an RNA hairpin structure
What allows viral genome to be associated with the plasma membrane?
→Myristoylation of Glycines in the MA domain of Gag
What is required for virus budding?
→HIV-1 PT(S)AP motif
What is abscission?
→organisation of all the proteins that pushes viral protein into cytoplasm
What allows abscission of viral release?
→The ESCRT machinery is hijacked by HIV
What are the components of the ESCRT machinery?
→Gag
→Tsg101
→Alix
→ESCRT-II CHMP4A
What causes the release of proteins from Gag and Gag-Pol polyproteins?
→Protease
→viral proteins are cut up into individual proteins allowing them to reorganise
